Publications by authors named "José L Moreno"

57 Publications

Global homogenization of the structure and function in the soil microbiome of urban greenspaces.

Sci Adv 2021 Jul 9;7(28). Epub 2021 Jul 9.

GEMA Center for Genomics, Ecology and Environment, Faculty of Interdisciplinary Studies, Universidad Mayor, Santiago, Chile.

The structure and function of the soil microbiome of urban greenspaces remain largely undetermined. We conducted a global field survey in urban greenspaces and neighboring natural ecosystems across 56 cities from six continents, and found that urban soils are important hotspots for soil bacterial, protist and functional gene diversity, but support highly homogenized microbial communities worldwide. Urban greenspaces had a greater proportion of fast-growing bacteria, algae, amoebae, and fungal pathogens, but a lower proportion of ectomycorrhizal fungi than natural ecosystems. These urban ecosystems also showed higher proportions of genes associated with human pathogens, greenhouse gas emissions, faster nutrient cycling, and more intense abiotic stress than natural environments. City affluence, management practices, and climate were fundamental drivers of urban soil communities. Our work paves the way toward a more comprehensive global-scale perspective on urban greenspaces, which is integral to managing the health of these ecosystems and the well-being of human populations.
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http://dx.doi.org/10.1126/sciadv.abg5809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270485PMC
July 2021

Differential mechanisms of change in motivational interviewing versus health education for smoking cessation induction.

Psychol Addict Behav 2021 Apr 1. Epub 2021 Apr 1.

Division of Health Services and Outcomes Research.

To determine if Motivational Interviewing (MI) versus health education (HE) elicited different types of client language and whether these differences were associated with outcomes in a randomized clinical trial (RCT) for cessation induction among people who smoke with low motivation to quit. A secondary data analysis was conducted using data from the MI and HE arms of a trial in which people who smoke ( = 202) with low desire to quit were randomly assigned to four sessions of MI, HE or brief advice. Mediation analyses examined two types of client language: change talk (CT) and a novel form of client speech called "learning talk" (LT). Outcomes were assessed at baseline, 3 and 6 months. With HE as the reference group, MI resulted in greater CT ( = 3.0, 95% CI: 1.7-5.5) which was associated with better outcomes (average = .34, = .13) and HE resulted in greater LT ( = .05, 95% CI: .02-.10) which was also associated with better outcomes (average = .42, = .08). Indirect parallel mediation effects on quit attempts were significant for both MI-CT ( = 1.4, 95% CI: 1.1-1.7) and HE-LT ( = .4, 95% CI: .2-.7). MI and HE were both efficacious via different pathways to change, confirming the utility of MI in this RCT as well as highlighting the potential of HE based on the "5R's" for smoking cessation. These findings emphasize the value of exploring theorized mechanisms of action of interventions evaluated in RCTs. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/adb0000720DOI Listing
April 2021

Transoral approach in facial penetrating trauma - importance of multidisciplinary management and nutritional support a case report.

Trauma Case Rep 2021 Apr 10;32:100421. Epub 2021 Feb 10.

General Surgery Resident PGY2, Universidad Católica del Ecuador, Eugenio Espejo Hospital of Specialties, Ecuador.

The high incidence and prevalence of facial trauma makes it important to consider related injuries and possible complications that may arise as a result. Penetrating trauma to the face, although not common, requires a surgeon with knowledge of the anatomy and physiology of the injured area and injury patterns. We present a case of penetrating trauma to the face that was caused by a blunt object (stake) resulting from the felling of a palm tree. We describe the transoral management that was performed and the multidisciplinary support that allowed optimal management of the injury without complications, including functional or aesthetic sequelae.
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http://dx.doi.org/10.1016/j.tcr.2021.100421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905237PMC
April 2021

Arthroscopy-Assisted Latissimus Dorsi Transfer for Irreparable Subscapularis Tears.

Arthrosc Tech 2021 Jan 19;10(1):e49-e53. Epub 2020 Dec 19.

Hospital Clínico Mutual de Seguridad CChC, Santiago, Chile.

Irreparable tears of the subscapularis (SS) tendon are difficult to manage and represent a challenge for the surgeon, especially in young and active patients. They are associated with a horizontal imbalance of the shoulder, causing pain and limitation of active internal rotation. Historically, the alternative for these patients has been transfer of the pectoralis major, with all its variations, total or partial, up or under the conjoint tendon. However, this transfer has mechanical disadvantages, especially related to the vector of traction, because it originates in the anterior region of the chest. In 2013, Elhassan and colleagues demonstrated in cadavers the technical feasibility and neurological safety of performing transfers of the latissimus dorsi (LD) to the lesser tuberosity to reconstruct irreparable lesions of the subscapularis. This option, compared with alternatives, has superior biomechanical advantages such as a similar vector of traction, originating from lower and posterior to the thorax, in addition to involving a synergistic muscle in action. In early 2016, Kany and colleagues first published a study of 5 patients undergoing arthroscopic assisted LD to SS transfer, with promising results. Our purpose is to present an arthroscopically assisted latissimus dorsi transfer technique in patients with irreparable subscapularis rupture.
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http://dx.doi.org/10.1016/j.eats.2020.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823060PMC
January 2021

Organic amendments exacerbate the effects of silver nanoparticles on microbial biomass and community composition of a semiarid soil.

Sci Total Environ 2020 Nov 15;744:140919. Epub 2020 Jul 15.

CEBAS-CSIC. Department of Soil and Water Conservation. Campus Universitario de Espinardo, 30100 Murcia, Spain.

Increased utilization of silver nanoparticles (AgNPs) can result in an accumulation of these particles in the environment. The potential detrimental effects of AgNPs in soil may be associated with the low fertility of soils in semiarid regions that are usually subjected to restoration through the application of organic amendments. Microbial communities are responsible for fundamental processes related to soil fertility, yet the potential impacts of low and realistic AgNPs concentrations on soil microorganisms are still unknown. We studied the effects of realistic citrate-stabilized AgNPs concentrations (0.015 and 1.5 μg kg) at two exposure times (7 and 30 days) on a sandy clay loam Mediterranean soil unamended (SU) and amended with compost (SA). We assessed soil microbial biomass (microbial fatty acids), soil enzyme activities (urease, β-glucosidase, and alkaline phosphatase), and composition of the microbial community (bacterial 16S rRNA gene and fungal ITS2 sequencing) in a microcosm experiment. In the SA, the two concentrations of AgNPs significantly decreased the bacterial biomass after 7 days of incubation. At 30 days of incubation, only a significant decrease in the Gram+ was observed at the highest AgNPs concentration. In contrast, in the SU, there was a significant increase in bacterial biomass after 30 days of incubation at the lowest AgNPs concentration. Overall, we found that fungal biomass was more resistant to AgNPs than bacterial biomass, in both SA and SU. Further, the AgNPs changed the composition of the soil bacterial community in SA, the relative abundance of some bacterial taxa in SA and SU, and fungal richness in SU at 30 days of incubation. However, AgNPs did not affect the activity of extracellular enzymes. This study demonstrates that the exposure time and organic amendments modulate the effects of realistic concentrations of AgNPs in the biomass and composition of the microbial community of a Mediterranean soil.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140919DOI Listing
November 2020

Sequence Changes Modulate Peptoid Self-Association in Water.

Front Chem 2020 23;8:260. Epub 2020 Apr 23.

Department of Chemistry & Biochemistry, Santa Clara University, Santa Clara, CA, United States.

Peptoids, -substituted glycine oligomers, are a class of diverse and sequence-specific peptidomimetics with wide-ranging applications. Advancing the functional repertoire of peptoids to emulate native peptide and protein functions requires engineering peptoids that adopt regular secondary and tertiary structures. An understanding of how changes to peptoid sequence change structural features, particularly in water-soluble systems, is underdeveloped. To address this knowledge gap, five 15-residue water-soluble peptoids that include naphthalene-functionalized side chains were designed, prepared, and subjected to a structural study using a palette of techniques. Peptoid sequence designs were based on a putative amphiphilic helix peptoid bearing structure-promoting ()--(1-naphthylethyl)glycine residues whose self-association in water has been studied previously. New peptoid variants reported here include sequence changes that influenced peptoid conformational flexibility, functional group patterning (amphiphilicity), and hydrophobicity. Peptoid structures were evaluated and compared using circular dichroism spectroscopy, fluorescence spectroscopy, and size exclusion chromatography. Spectral data confirmed that sequence changes alter peptoids' degree of assembly and the organization of self-assembled structures in aqueous solutions. Insights gained in these studies will inform the design of new water-soluble peptoids with regular structural features, including desirable higher-order (tertiary and quaternary) structural features.
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http://dx.doi.org/10.3389/fchem.2020.00260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191062PMC
April 2020

Gut microbiota manipulation during the prepubertal period shapes behavioral abnormalities in a mouse neurodevelopmental disorder model.

Sci Rep 2020 03 13;10(1):4697. Epub 2020 Mar 13.

Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA.

Previous studies demonstrate an association between activation of the maternal immune system during pregnancy and increased risk of neurodevelopmental psychiatric conditions, such as schizophrenia and autism, in the offspring. Relatively recent findings also suggest that the gut microbiota plays an important role in shaping brain development and behavior. Here we show that maternal immune activation (MIA) accomplished by infection with a mouse-adapted influenza virus during pregnancy induced up-regulation of frontal cortex serotonin 5-HT receptor (5-HTR) density in the adult offspring, a phenotype previously observed in postmortem frontal cortex of schizophrenic subjects. 5-HTR agonist-induced head-twitch behavior was also augmented in this preclinical mouse model. Using the novel object recognition (NOR) test to evaluate cognitive performance, we demonstrate that MIA induced NOR deficits in adult offspring. Oral antibiotic treatment of prepubertal mice prevented this cognitive impairment, but not increased frontal cortex 5-HTR density or psychedelic-induced head-twitch behavior in adult MIA offspring. Additionally, gut microbiota transplantation from MIA mice produced behavioral deficits in antibiotic-treated mock mice. Adult MIA offspring displayed altered gut microbiota, and relative abundance of specific components of the gut microbiota, including Ruminococcaceae, correlated with frontal cortex 5-HTR density. Together, these findings provide a better understanding of basic mechanisms by which prenatal insults impact offspring brain function, and suggest gut-brain axis manipulation as a potential therapeutic approach for neurodevelopmental psychiatric conditions.
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http://dx.doi.org/10.1038/s41598-020-61635-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070045PMC
March 2020

Environmentally relevant concentrations of silver nanoparticles diminish soil microbial biomass but do not alter enzyme activities or microbial diversity.

J Hazard Mater 2020 06 4;391:122224. Epub 2020 Feb 4.

CEBAS-CSIC. Department of Soil and Water Conservation, Campus Universitario de Espinardo, 30100, Murcia, Spain.

The increasing use of silver nanoparticles (AgNPs) due to their well-known antimicrobial activity, has led to their accumulation in soil ecosystems. However, the impact of environmental realistic concentrations of AgNPs on the soil microbial community has been scarcely studied. In this work, we have assessed the impact of AgNPs, that mimic real concentrations in nature, on tropical soils cultivated with Coffea arabica under conventional and organic management systems. We evaluated the biomass, extracellular enzyme activities, and diversity of the soil microbial community, in a microcosm experiment as a function of time. After seven days of incubation, we found an increase in microbial biomass in an AgNPs-concentration-independent manner. In contrast, after 60-day-incubation, there was a decrease in Gram+ and actinobacterial biomass, in both soils and all AgNPs concentrations. Soil physico-chemical properties and enzyme activities were not affected overall by AgNPs. Regarding the microbial community composition, only some differences in the relative abundance at phylum and genus level in the fungal community were observed. Our results suggest that environmental concentrations of AgNPs affected microbial biomass but had little impact on microbial diversity and may have little effects on the soil biogeochemical cycles mediated by extracellular enzyme activities.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122224DOI Listing
June 2020

Revised Pharmacophore Model for 5-HT Receptor Antagonists Derived from the Atypical Antipsychotic Agent Risperidone.

ACS Chem Neurosci 2019 05 16;10(5):2318-2331. Epub 2019 Jan 16.

Department of Physiology and Biophysics , Virginia Commonwealth University School of Medicine , Richmond , Virginia 23298 , United States.

Pharmacophore models for 5-HT receptor antagonists consist of two aromatic/hydrophobic regions at a given distance from a basic amine. We have previously shown that both aromatic/hydrophobic moieties are unnecessary for binding or antagonist action. Here, we deconstructed the 5-HT receptor antagonist/serotonin-dopamine antipsychotic agent risperidone into smaller structural segments that were tested for 5-HT receptor affinity and function. We show, again, that the entire risperidone structure is unnecessary for retention of affinity or antagonist action. Replacement of the 6-fluoro-3-(4-piperidinyl)-1,2-benz[ d]isoxazole moiety by isosteric tryptamines resulted in retention of affinity and antagonist action. Additionally, 3-(4-piperidinyl)-1,2-benz[ d]isoxazole (10), which represents less than half the structural features of risperidone, retains both affinity and antagonist actions. 5-HT receptor homology modeling/docking studies suggest that 10 binds in a manner similar to risperidone and that there is a large cavity to accept various N-substituted analogues of 10 such as risperidone and related agents. Alterations of this "extended" moiety improve receptor binding and functional potency. We propose a new risperidone-based pharmacophore for 5-HT receptor antagonist action.
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http://dx.doi.org/10.1021/acschemneuro.8b00637DOI Listing
May 2019

Negative Life Events (NLEs) Contributing to Psychological Distress, Pain, and Disability in a U.S. Military Sample.

Mil Med 2019 01;184(1-2):e148-e155

Department of Psychiatry, University of Texas Health San Antonio, 8300 Floyd Curl Dr., San Antonio, TX.

Introduction: The objective was to explore how negative life events (NLEs, e.g., litigation related to pain and disability, failing most recent physical fitness test, and financial difficulties) are related to pain coping and psychological adjustment to pain in active duty military personnel.

Materials And Methods: Data were gathered as part of the Evaluation of Suicidality, Cognitions, and Pain Experience study, a DoD-funded cross-sectional assessment of chronic pain and emotional coping among a cohort of military members. The investigators examined data from 147 respondents with complete survey and pain assessment data.

Results: The sample was active duty, male (62.6%), in a relationship or married (83.0%), and had children (68.7%). The majority of the sample endorsed zero NLEs (72.0%); 23.8% endorsed one NLE, 4.2% endorsed two NLEs, and no one endorsed all three NLEs. A significantly higher proportion of participants endorsing one or more NLEs reported suicidal ideation compared to those who reported no NLEs (χ2(2) = 8.61, p = 0.014). A higher number of endorsed NLEs coincided with higher symptom severity related to psychosocial distress (depression, thwarted belongingness, perceived burdensomeness, PTSD, and suicide cognitions) and poor pain coping (rumination, helplessness, and less acceptance of chronic pain).

Conclusions: Findings revealed that NLEs may impart a significant burden on military pain sufferers. Greater numbers of endorsed NLEs are associated with increased psychosocial distress and poor pain coping. Future longitudinal studies examining long-term psychosocial distress/poor pain coping as related to NLEs would help to elaborate the long-term consequences of NLEs on pain coping and psychosocial distress.
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http://dx.doi.org/10.1093/milmed/usy259DOI Listing
January 2019

Work disability in Argentinian patients with systemic lupus erythematosus is prevalent and it is due to ethnic, socioeconomic and disease-related factors.

Int J Rheum Dis 2018 Nov 2;21(11):2019-2027. Epub 2018 Apr 2.

Hospital de San Isidro, Ciudad de San Isidro, Argentina.

Objective: To study the prevalence and the associated factors of work disability (WD) in systemic lupus erythematosus (SLE) patients.

Methods: A sample of 419 SLE patients from an observational cross-sectional multicenter study was included. Sociodemographic features, disease characteristics, comorbidities, quality of life, unhealthy behaviors, and work-related factors were measured in a standardized interview. Work disability was defined by patient self-report of not being able to work because of SLE. To identify variables associated with work disability, two different multivariate regression models using a stepwise backward method were performed.

Results: Prevalence of WD due to SLE was 24.3%. Eighty-nine percent were female and 51% were Caucasians. Mean disease duration was 8.9 ± 7.2 years, and median System Lupus International Collaborating Clinics/American College of Rheumatology damage index SLICC-SDI was 1.5 (range 0-17). In stepwise multivariate logistic regression, living below the poverty line (odds ratio [OR] = 4.65), less than 12 years of education (OR = 2.84), Mestizo ethnicity (OR = 1.94) and SLICC-SDI (OR = 1.25) were predictors of WD. A second model was performed including patient-derived measures; in this model sedentary lifestyle (OR = 2.69) and lower emotional health domain score of the Lupus Quality of Life (LupusQoL) questionnaire (OR = 1.03) were found to be associated to WD and a higher score in LupusQoL physical health domain (OR = 0.93) was protective.

Conclusion: The prevalence of WD in Argentinian SLE patients was 24.3%. WD was associated with ethnic (Mestizo), socioeconomic (poverty) and disease-related factors. Patient-related outcomes such us sedentary lifestyle and poor emotional quality of life were also associated with WD.
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http://dx.doi.org/10.1111/1756-185X.13269DOI Listing
November 2018

Antipsychotic-induced Hdac2 transcription via NF-κB leads to synaptic and cognitive side effects.

Nat Neurosci 2017 Sep 7;20(9):1247-1259. Epub 2017 Aug 7.

Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.

Antipsychotic drugs remain the standard for schizophrenia treatment. Despite their effectiveness in treating hallucinations and delusions, prolonged exposure to antipsychotic medications leads to cognitive deficits in both schizophrenia patients and animal models. The molecular mechanisms underlying these negative effects on cognition remain to be elucidated. Here we demonstrate that chronic antipsychotic drug exposure increases nuclear translocation of NF-κB in both mouse and human frontal cortex, a trafficking event triggered via 5-HT-receptor-dependent downregulation of the NF-κB repressor IκBα. This upregulation of NF-κB activity led to its increased binding at the Hdac2 promoter, thereby augmenting Hdac2 transcription. Deletion of HDAC2 in forebrain pyramidal neurons prevented the negative effects of antipsychotic treatment on synaptic remodeling and cognition. Conversely, virally mediated activation of NF-κB signaling decreased cortical synaptic plasticity via HDAC2. Together, these observations may aid in developing therapeutic strategies to improve the outcome of schizophrenia treatment.
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http://dx.doi.org/10.1038/nn.4616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675106PMC
September 2017

Cellular circadian oscillators in the suprachiasmatic nucleus remain coupled in the absence of connexin-36.

Neuroscience 2017 08 31;357:1-11. Epub 2017 May 31.

Department of Psychiatry and Center for Circadian Biology, University of California, San Diego, La Jolla, CA, United States; Veterans Affairs San Diego Healthcare System, San Diego, CA, United States.

In mammals, the master circadian clock resides in the suprachiasmatic nucleus (SCN). The SCN is characterized by robust circadian oscillations of clock gene expression and neuronal firing. The synchronization of circadian oscillations among individual cells in the SCN is attributed to intercellular coupling. Previous studies have shown that gap junctions, specifically those composed of connexin-36 (Cx36) subunits, are required for coupling of electrical firing among SCN neurons at a time scale of milliseconds. However, it remains unknown whether Cx36 gap junctions also contribute to coupling of circadian (∼24h) rhythms of clock gene expression. Here, we investigated circadian expression patterns of the clock gene Period 2 (Per2) in the SCN of Cx36-deficient mice using luminometry and single-cell bioluminescence imaging. Surprisingly, we found that synchronization of circadian PER2 expression rhythms is maintained in SCN explants from Cx36-deficient mice. Since Cx36 expression levels change with age, we also tested circadian running-wheel behavior of juvenile (3-4weeks old) and adult (9-30weeks old) Cx36-deficient mice. We found that impact of connexin-36 expression on circadian behavior changes greatly during postnatal development. However, consistent with the intact synchrony among SCN cells in cultured explants, Cx36-deficient mice had intact locomotor circadian rhythms, although adults displayed a lengthened period in constant darkness. Our data indicate that even though Cx36 may be required for electrical coupling of SCN cells, it does not affect coupling of molecular clock gene rhythms. Thus, electrical coupling of neurons and coupling of circadian clock gene oscillations can be regulated independently in the SCN.
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http://dx.doi.org/10.1016/j.neuroscience.2017.05.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556374PMC
August 2017

Executive function fails to predict smoking outcomes in a clinical trial to motivate smokers to quit.

Drug Alcohol Depend 2017 06 13;175:227-231. Epub 2017 Apr 13.

Center for Children's Healthy Lifestyles and Nutrition, Children's Mercy Kansas City,2401 Gillham Rd., Kansas City, MO 64108, USA.

Background: Executive function (EF) is considered an important mediator of health outcomes. It is hypothesized that those with better EF are more likely to succeed in turning their intentions into actual health behaviors. Prior studies indicate EF is associated with smoking cessation. Experimental and longitudinal studies, however, have yielded mixed results. Few studies have examined whether EF predicts post-treatment smoking behavior. Fewer still have done so prospectively in a large trial. We sought to determine if EF predicts quit attempts and cessation among community smokers in a large randomized trial evaluating the efficacy of motivational interventions for encouraging cessation.

Methods: Participants (N=255) completed a baseline assessment that included a cognitive battery to assess EF (Oral Trail Making Test B, Stroop, Controlled Oral Word Association Test). Participants were then randomized to 4 sessions of Motivational Interviewing or Health Education or one session of Brief Advice to quit. Quit attempts and cessation were assessed at weeks 12 and 26.

Results: In regression analyses, none of the EF measures were statistically significant predictors of quit attempts or cessation (all ps>0.20).

Conclusions: Our data did not support models of health behavior that emphasize EF as a mediator of health outcomes. Methodological shortcomings weaken the existing support for an association between EF and smoking behavior. We suggest methodological improvements that could help move this potentially important area of research forward.
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http://dx.doi.org/10.1016/j.drugalcdep.2017.01.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425305PMC
June 2017

Differences in 5-HT2A and mGlu2 Receptor Expression Levels and Repressive Epigenetic Modifications at the 5-HT2A Promoter Region in the Roman Low- (RLA-I) and High- (RHA-I) Avoidance Rat Strains.

Mol Neurobiol 2018 03 6;55(3):1998-2012. Epub 2017 Mar 6.

Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Building 11B, 2nd floor, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark.

The serotonin 2A (5-HT) and metabotropic glutamate 2 (mGlu2) receptors regulate each other and are associated with schizophrenia. The Roman high- (RHA-I) and the Roman low- (RLA-I) avoidance rat strains present well-differentiated behavioral profiles, with the RHA-I strain emerging as a putative genetic rat model of schizophrenia-related features. The RHA-I strain shows increased 5-HT and decreased mGlu2 receptor binding levels in prefrontal cortex (PFC). Here, we looked for differences in gene expression and transcriptional regulation of these receptors. The striatum (STR) was included in the analysis. 5-HT, 5-HT, and mGlu2 mRNA and [H]ketanserin binding levels were measured in brain homogenates. As expected, 5-HT binding was significantly increased in PFC in the RHA-I rats, while no difference in binding was observed in STR. Surprisingly, 5-HT gene expression was unchanged in PFC but significantly decreased in STR. mGlu2 receptor gene expression was significantly decreased in both PFC and STR. No differences were observed for the 5-HT receptor. Chromatin immunoprecipitation assay revealed increased trimethylation of histone 3 at lysine 27 (H3K27me3) at the promoter region of the HTR2A gene in the STR. We further looked at the Akt/GSK3 signaling pathway, a downstream point of convergence of the serotonin and glutamate system, and found increased phosphorylation levels of GSK3β at tyrosine 216 and increased β-catenin levels in the PFC of the RHA-I rats. These results reveal region-specific regulation of the 5-HT receptor in the RHA-I rats probably due to absence of mGlu2 receptor that may result in differential regulation of downstream pathways.
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http://dx.doi.org/10.1007/s12035-017-0457-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587367PMC
March 2018

Validation of schizophrenia gene expression profile in a preclinical model of maternal infection during pregnancy.

Schizophr Res 2017 11 12;189:217-218. Epub 2017 Feb 12.

Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298, USA. Electronic address:

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http://dx.doi.org/10.1016/j.schres.2017.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554460PMC
November 2017

Motivational interviewing and the decisional balance procedure for cessation induction in smokers not intending to quit.

Addict Behav 2017 01 31;64:171-178. Epub 2016 Aug 31.

Center for Children's Healthy Lifestyles & Nutrition, Children's Mercy Hospitals and Clinics, Department of Pediatrics, University of Missouri-Kansas City School of Medicine, 2401 Gillham Road, Kansas City, MO 64108, United States. Electronic address:

Introduction: The decisional balance (DB) procedure examines the pros and cons of behavior change and was considered a component in early formulations of Motivational Interviewing (MI). However, there is controversy and conflicting findings regarding the use of a DB exercise within the treatment of addictions and a need to clarify the role of DB as a component of MI.

Methods: College tobacco smokers (N=82) with no intentions on quitting were randomly assigned to receive a single counseling session of either Motivational Interviewing using only the decisional balance component (MIDB), or health education around smoking cessation (HE). Assessments were obtained at baseline, immediately post-treatment, 1week, and 4weeks.

Results: Compared to HE, the MIDB sessions scored significantly higher on the Motivational Interviewing Treatment Integrity (MITI) scale (all standardized differences d>1, p<0.001). Unexpectedly, self-report Pros of smoking scores increased for MIDB but decreased for HE (MIDB vs HE standardized difference d=0.5; 95%CI 0.1 to 1.0, p=0.021). Both groups showed significant reductions in smoking rates and increases in motivation to quit, quit attempts, and self-reported abstinence, with no significant group differences. Changes in the Pros of smoking were correlated with MITI scores, but not with cessation outcomes. In contrast, increases in the Cons of smoking and therapeutic alliance were predictive of better cessation outcomes.

Conclusions: The decisional balance exercise as formulated by earlier versions of MI may be counter-productive and cautions around its use are warranted. Instead, improved cessation outcomes appear associated with increasing perceived benefits of quitting and positive therapeutic alliance.
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http://dx.doi.org/10.1016/j.addbeh.2016.08.036DOI Listing
January 2017

HSV-Mediated Transgene Expression of Chimeric Constructs to Study Behavioral Function of GPCR Heteromers in Mice.

J Vis Exp 2016 07 9(113). Epub 2016 Jul 9.

Department of Psychiatry, Icahn School of Medicine at Mount Sinai; Department of Neurology, Icahn School of Medicine at Mount Sinai; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai; Department of Physiology and Biophysics, Virginia Commonwealth University Medical School;

The heteromeric receptor complex between 5-HT2A and mGlu2 has been implicated in some of the behavioral phenotypes in mouse models of psychosis(1,2). Consequently, investigation of structural details of the interaction between 5-HT2A and mGlu2 affecting schizophrenia-related behaviors represents a powerful translational tool. As previously shown, the head-twitch response (HTR) in mice is elicited by hallucinogenic drugs and this behavioral response is absent in 5-HT2A knockout (KO) mice(3,4). Additionally, by conditionally expressing the 5-HT2A receptor only in cortex, it was demonstrated that 5-HT2A receptor-dependent signaling pathways on cortical pyramidal neurons are sufficient to elicit head-twitch behavior in response to hallucinogenic drugs(3). Finally, it has been shown that the head-twitch behavioral response induced by the hallucinogens DOI and lysergic acid diethylamide (LSD) is significantly decreased in mGlu2-KO mice(5). These findings suggest that mGlu2 is at least in part necessary for the 5-HT2A receptor-dependent psychosis-like behavioral effects induced by LSD-like drugs. However, this does not provide evidence as to whether the 5-HT2A-mGlu2 receptor complex is necessary for this behavioral phenotype. To address this question, herpes simplex virus (HSV) constructs to express either mGlu2 or mGlu2ΔTM4N (mGlu2/mGlu3 chimeric construct that does not form the 5-HT2A-mGlu2 receptor complex) in the frontal cortex of mGlu2-KO mice were used to examine whether this GPCR heteromeric complex is needed for the behavioral effects induced by LSD-like drugs(6).
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http://dx.doi.org/10.3791/53717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993366PMC
July 2016

The active microbial diversity drives ecosystem multifunctionality and is physiologically related to carbon availability in Mediterranean semi-arid soils.

Mol Ecol 2016 Sep 26;25(18):4660-73. Epub 2016 Aug 26.

Department of Molecular Systems Biology, Helmholtz-Centre for Environmental Research - UFZ, Permoserstr. 15, 04318, Leipzig, Germany.

Biogeochemical processes and ecosystemic functions are mostly driven by soil microbial communities. However, most methods focus on evaluating the total microbial community and fail to discriminate its active fraction which is linked to soil functionality. Precisely, the activity of the microbial community is strongly limited by the availability of organic carbon (C) in soils under arid and semi-arid climate. Here, we provide a complementary genomic and metaproteomic approach to investigate the relationships between the diversity of the total community, the active diversity and ecosystem functionality across a dissolved organic carbon (DOC) gradient in southeast Spain. DOC correlated with the ecosystem multifunctionality index composed by soil respiration, enzyme activities (urease, alkaline phosphatase and β-glucosidase) and microbial biomass (phospholipid fatty acids, PLFA). This study highlights that the active diversity (determined by metaprotoemics) but not the diversity of the whole microbial community (evaluated by amplicon gene sequencing) is related to the availability of organic C and it is also connected to the ecosystem multifunctionality index. We reveal that DOC shapes the activities of bacterial and fungal populations in Mediterranean semi-arid soils and determines the compartmentalization of functional niches. For instance, Rhizobales thrived at high-DOC sites probably fuelled by metabolism of one-C compounds. Moreover, the analysis of proteins involved in the transport and metabolism of carbohydrates revealed that Ascomycota and Basidiomycota occupied different nutritional niches. The functional mechanisms for niche specialization were not constant across the DOC gradient.
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http://dx.doi.org/10.1111/mec.13783DOI Listing
September 2016

Reformulating a Pharmacophore for 5-HT2A Serotonin Receptor Antagonists.

ACS Chem Neurosci 2016 09 19;7(9):1292-9. Epub 2016 Jul 19.

Department of Physiology and Biophysics, School of Medicine, and ‡Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University , Richmond, Virginia 23298, United States.

Several pharmacophore models have been proposed for 5-HT2A serotonin receptor antagonists. These typically consist of two aromatic/hydrophobic moieties separated by a given distance from each other, and from a basic amine. Although specified distances might vary, the models are relatively similar in their general construction. Because our preliminary data indicated that two aromatic (hydrophobic) moieties might not be required for such action, we deconstructed the serotonin-dopamine antipsychotic agent risperidone (1) into four smaller structural fragments that were thoroughly examined in 5-HT2A receptor binding and functional (i.e., two-electrode voltage clamp (TEVC) and intracellular calcium release) assays. It was apparent that truncated risperidone analogues behaved as antagonists. In particular, 6-fluoro-3-(1-methylpiperidin-4-yl)benzisoxazole (4) displayed high affinity for 5-HT2A receptors (Ki of ca. 12 nM) relative to risperidone (Ki of ca. 5 nM) and behaved as a potent 5-HT2A serotonin receptor antagonist. These results suggest that multiple aromatic (hydrophobic) moieties are not essential for high-affinity 5-HT2A receptor binding and antagonist activity and that current pharmacophore models for such agents are very much in need of revision.
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http://dx.doi.org/10.1021/acschemneuro.6b00162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333931PMC
September 2016

Cross-signaling in metabotropic glutamate 2 and serotonin 2A receptor heteromers in mammalian cells.

Pflugers Arch 2016 05 16;468(5):775-93. Epub 2016 Jan 16.

Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA.

We previously reported that co-expression of the Gi-coupled metabotropic glutamate receptor 2 (mGlu2R) and the Gq-coupled serotonin (5-HT) 2A receptor (2AR) in Xenopus oocytes (Fribourg et al. Cell 147:1011-1023, 2011) results in inverse cross-signaling, where for either receptor, strong agonists suppress and inverse agonists potentiate the signaling of the partner receptor. Importantly, through this cross-signaling, the mGlu2R/2AR heteromer integrates the actions of psychedelic and antipsychotic drugs. To investigate whether mGlu2R and 2AR can cross-signal in mammalian cells, we stably co-expressed them in HEK293 cells along with the GIRK1/GIRK4 channel, a reporter of Gi and Gq signaling activity. Crosstalk-positive clones were identified by Fura-2 calcium imaging, based on potentiation of 5-HT-induced Ca(2+) responses by the inverse mGlu2/3R agonist LY341495. Cross-signaling from both sides of the complex was confirmed in representative clones by using the GIRK channel reporter, both in whole-cell patch-clamp and in fluorescence assays using potentiometric dyes, and further established by competition binding assays. Notably, only 25-30 % of the clones were crosstalk-positive. The crosstalk-positive phenotype correlated with (a) increased colocalization of the two receptors at the cell surface, (b) lower density of mGlu2R binding sites and higher density of 2AR binding sites in total membrane preparations, and (c) higher ratios of mGlu2R/2AR normalized surface protein expression. Consistent with our results in Xenopus oocytes, a combination of ligands targeting both receptors could elicit functional crosstalk in a crosstalk-negative clone. Crosstalk-positive clones can be used in high-throughput assays for identification of antipsychotic drugs targeting this receptor heterocomplex.
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http://dx.doi.org/10.1007/s00424-015-1780-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842341PMC
May 2016

Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia.

Sci Signal 2016 Jan 12;9(410):ra5. Epub 2016 Jan 12.

Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) can form multiprotein complexes (heteromers), which can alter the pharmacology and functions of the constituent receptors. Previous findings demonstrated that the Gq/11-coupled serotonin 5-HT2A receptor and the Gi/o-coupled metabotropic glutamate 2 (mGlu2) receptor-GPCRs that are involved in signaling alterations associated with psychosis-assemble into a heteromeric complex in the mammalian brain. In single-cell experiments with various mutant versions of the mGlu2 receptor, we showed that stimulation of cells expressing mGlu2-5-HT2A heteromers with an mGlu2 agonist led to activation of Gq/11 proteins by the 5-HT2A receptors. For this crosstalk to occur, one of the mGlu2 subunits had to couple to Gi/o proteins, and we determined the relative location of the Gi/o-contacting subunit within the mGlu2 homodimer of the heteromeric complex. Additionally, mGlu2-dependent activation of Gq/11, but not Gi/o, was reduced in the frontal cortex of 5-HT2A knockout mice and was reduced in the frontal cortex of postmortem brains from schizophrenic patients. These findings offer structural insights into this important target in molecular psychiatry.
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http://dx.doi.org/10.1126/scisignal.aab0467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819166PMC
January 2016

A Randomized Trial of Motivational Interviewing: Cessation Induction Among Smokers With Low Desire to Quit.

Am J Prev Med 2016 May 23;50(5):573-583. Epub 2015 Dec 23.

Department of Psychology, University of Missouri-Kansas City, Kansas City, Missouri.

Introduction: Despite limitations in evidence, the current Clinical Practice Guideline advocates Motivational Interviewing for smokers not ready to quit. This study evaluated the efficacy of Motivational Interviewing for inducing cessation-related behaviors among smokers with low motivation to quit.

Design: Randomized clinical trial.

Setting/participants: Two-hundred fifty-five daily smokers reporting low desire to quit smoking were recruited from an urban community during 2010-2011 and randomly assigned to Motivational Interviewing, health education, or brief advice using a 2:2:1 allocation. Data were analyzed from 2012 to 2014.

Intervention: Four sessions of Motivational Interviewing utilized a patient-centered communication style that explored patients' own reasons for change. Four sessions of health education provided education related to smoking cessation while excluding elements characteristic of Motivational Interviewing. A single session of brief advice consisted of brief, personalized advice to quit.

Main Outcomes Measures: Self-reported quit attempts; smoking abstinence (biochemically verified); use of cessation pharmacotherapies; motivation; and confidence to quit were assessed at baseline and 3- and 6-month follow-ups.

Results: Unexpectedly, no significant differences emerged between groups in the proportion who made a quit attempt by 6-month follow-up (Motivational Interviewing, 52.0%; health education, 60.8%; brief advice, 45.1%; p=0.157). Health education had significantly higher biochemically verified abstinence rates at 6 months (7.8%) than brief advice (0.0%) (8% risk difference, 95% CI=3%, 13%, p=0.003), with the Motivational Interviewing group falling in between (2.9% abstinent, 3% risk difference, 95% CI=0%, 6%, p=0.079). Both Motivational Interviewing and health education groups showed greater increases in cessation medication use, motivation, and confidence to quit relative to brief advice (all p<0.05), and health education showed greater increases in motivation relative to Motivational Interviewing (Cohen's d=0.36, 95% CI=0.12, 0.60).

Conclusions: Although Motivational Interviewing was generally more efficacious than brief advice in inducing cessation behaviors, health education appeared the most efficacious. These results highlight the need to identify the contexts in which Motivational Interviewing may be most efficacious and question recommendations to use Motivational Interviewing rather than other less complex cessation induction interventions.

Trial Registration: This study is registered at www.clinicaltrials.gov NCT01188018.
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http://dx.doi.org/10.1016/j.amepre.2015.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841713PMC
May 2016

The relationship between ART adherence and smoking status among HIV+ individuals.

AIDS Behav 2015 Apr;19(4):619-25

Department of Psychology, University of Missouri-Kansas City, 5030 Cherry Street, Cherry Hall Room 324, Kansas City, MO, 64110, USA,

Smoking is highly prevalent among HIV+ individuals and studies indicate that it may be associated with poor ART adherence, though the relationship is poorly understood. In addition little is known about interest in quitting among HIV+ smokers who are having adherence difficulties. We examined smoking and ART adherence among 203 HIV+ individuals enrolled in a randomized trial of interventions to increase ART adherence. Prior analyses indicated there were no overall treatment group effects. Smoking status and motivation to quit was assessed at baseline and ART adherence was assessed at week 12, 24, 36, and 48. Longitudinal generalized estimating equation analysis that controlled for treatment group revealed that smoking status was not significantly related to adherence over time. Motivation to quit was high with 58 % intending to quit in the next 6 months and 25 % intending to quit in the next 30 days. Findings suggest that smoking is not associated with adherence among those with adherence difficulties. However it does not diminish importance of addressing both behaviors especially given HIV+ smokers substantial interest in changing smoking behavior.
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http://dx.doi.org/10.1007/s10461-014-0978-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520428PMC
April 2015

Preclinical models of antipsychotic drug action.

Int J Neuropsychopharmacol 2013 Nov 10;16(10):2131-44. Epub 2013 Jun 10.

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.

One of the main obstacles faced by translational neuroscience is the development of animal models of psychiatric disorders. Behavioural pharmacology studies indicate that psychedelic drugs, such as lysergic acid diethylamide (LSD) and dissociative drugs, such as phencyclidine (PCP), induce in healthy human volunteers psychotic and cognitive symptoms that resemble some of those observed in schizophrenia patients. Serotonin 5-HT2A and metabotropic glutamate 2 receptors have been involved in the mechanism of action of psychedelic and dissociative drugs. Here we review recent advances using LSD-like and PCP-like drugs in rodent models that implicate these receptors in the neurobiology of schizophrenia and its treatment.
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http://dx.doi.org/10.1017/S1461145713000606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836391PMC
November 2013

G protein-coupled receptor heterocomplexes in neuropsychiatric disorders.

Prog Mol Biol Transl Sci 2013 ;117:187-205

Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, USA.

G protein-coupled receptors (or GPCRs) represent the largest family of membrane proteins in the human genome and are the target of approximately half of all therapeutic drugs. GPCRs contain a conserved structure of seven transmembrane domains. Their amino terminus is located extracellularly, whereas the carboxy terminus extends into the cytoplasm. Accumulating evidence suggests that GPCRs exist and function as monomeric entities. Nevertheless, more recent findings indicate that GPCRs can also form dimers or even higher order oligomers. The differential pharmacological and signaling properties of GPCR heteromeric complexes hint that their physiological effects may be different as compared to those obtained in tissue cultures that express a particular GPCR. In this chapter, we review current data on the role of GPCR heteromerization in receptor signaling, as well as its potential implication in neuropsychiatric disorders such as schizophrenia, depression, and Parkinson's disease.
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http://dx.doi.org/10.1016/B978-0-12-386931-9.00008-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844024PMC
December 2013

G protein-coupled receptor heterocomplexes in neuropsychiatric disorders.

Prog Mol Biol Transl Sci 2013 ;117:187-205

Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, USA.

G protein-coupled receptors (or GPCRs) represent the largest family of membrane proteins in the human genome and are the target of approximately half of all therapeutic drugs. GPCRs contain a conserved structure of seven transmembrane domains. Their amino terminus is located extracellularly, whereas the carboxy terminus extends into the cytoplasm. Accumulating evidence suggests that GPCRs exist and function as monomeric entities. Nevertheless, more recent findings indicate that GPCRs can also form dimers or even higher order oligomers. The differential pharmacological and signaling properties of GPCR heteromeric complexes hint that their physiological effects may be different as compared to those obtained in tissue cultures that express a particular GPCR. In this chapter, we review current data on the role of GPCR heteromerization in receptor signaling, as well as its potential implication in neuropsychiatric disorders such as schizophrenia, depression, and Parkinson's disease.
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http://dx.doi.org/10.1016/B978-0-12-386931-9.00008-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844024PMC
December 2013

Chronic treatment with LY341495 decreases 5-HT(2A) receptor binding and hallucinogenic effects of LSD in mice.

Neurosci Lett 2013 Mar 16;536:69-73. Epub 2013 Jan 16.

Department of Psychiatry, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1229, New York, NY 10029, United States.

Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT(2A) receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [(3)H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT(2A) agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT(2A) receptor-dependent hallucinogenic effects of LSD.
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http://dx.doi.org/10.1016/j.neulet.2012.12.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578056PMC
March 2013

Prenatal stress induces schizophrenia-like alterations of serotonin 2A and metabotropic glutamate 2 receptors in the adult offspring: role of maternal immune system.

J Neurosci 2013 Jan;33(3):1088-98

Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA.

It has been suggested that severe adverse life events during pregnancy increase the risk of schizophrenia in the offspring. The serotonin 5-HT(2A) and the metabotropic glutamate 2 (mGlu2) receptors both have been the target of considerable attention regarding schizophrenia and antipsychotic drug development. We tested the effects of maternal variable stress during pregnancy on expression and behavioral function of these two receptors in mice. Prenatal stress increased 5-HT(2A) and decreased mGlu2 expression in frontal cortex, a brain region involved in perception, cognition, and mood. This pattern of expression of 5-HT(2A) and mGlu2 receptors was consistent with behavioral alterations, including increased head-twitch response to the hallucinogenic 5-HT(2A) agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] and decreased mGlu2-dependent antipsychotic-like effect of the mGlu2/3 agonist LY379268 (1R,4R,5S,6R-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate) in adult, but not prepubertal, mice born to stressed mothers during pregnancy. Cross-fostering studies determined that these alterations were not attributable to effects of prenatal stress on maternal care. Additionally, a similar pattern of biochemical and behavioral changes were observed in mice born to mothers injected with polyinosinic:polycytidylic acid [poly(I:C)] during pregnancy as a model of prenatal immune activation. These data strengthen pathophysiological hypotheses that propose an early neurodevelopmental origin for schizophrenia and other psychiatric disorders.
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http://dx.doi.org/10.1523/JNEUROSCI.2331-12.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711555PMC
January 2013

Prenatal stress induces schizophrenia-like alterations of serotonin 2A and metabotropic glutamate 2 receptors in the adult offspring: role of maternal immune system.

J Neurosci 2013 Jan;33(3):1088-98

Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA.

It has been suggested that severe adverse life events during pregnancy increase the risk of schizophrenia in the offspring. The serotonin 5-HT(2A) and the metabotropic glutamate 2 (mGlu2) receptors both have been the target of considerable attention regarding schizophrenia and antipsychotic drug development. We tested the effects of maternal variable stress during pregnancy on expression and behavioral function of these two receptors in mice. Prenatal stress increased 5-HT(2A) and decreased mGlu2 expression in frontal cortex, a brain region involved in perception, cognition, and mood. This pattern of expression of 5-HT(2A) and mGlu2 receptors was consistent with behavioral alterations, including increased head-twitch response to the hallucinogenic 5-HT(2A) agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] and decreased mGlu2-dependent antipsychotic-like effect of the mGlu2/3 agonist LY379268 (1R,4R,5S,6R-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate) in adult, but not prepubertal, mice born to stressed mothers during pregnancy. Cross-fostering studies determined that these alterations were not attributable to effects of prenatal stress on maternal care. Additionally, a similar pattern of biochemical and behavioral changes were observed in mice born to mothers injected with polyinosinic:polycytidylic acid [poly(I:C)] during pregnancy as a model of prenatal immune activation. These data strengthen pathophysiological hypotheses that propose an early neurodevelopmental origin for schizophrenia and other psychiatric disorders.
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http://dx.doi.org/10.1523/JNEUROSCI.2331-12.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711555PMC
January 2013
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