Publications by authors named "Gabriele Ghisleni"

61 Publications

Brief cognitive behavioral therapy in pregnant women at risk of postpartum depression: Pre-post therapy study in a city in southern Brazil.

J Affect Disord 2021 Apr 30;290:15-22. Epub 2021 Apr 30.

Catholic University of Pelotas, Brazil; PQ CNPq, Brazil.

Background: Postpartum depression (PPD) affects a high number of women, often the first manifestation of a mood disorder that will occur later in life, bringing serious consequences for the patient and her offspring. Depression today is the leading cause of disability worldwide. The aim of this study was to evaluate the effectiveness of a preventive cognitive behavioral therapy (CBT) for PPD.

Methods: Pre-post therapy study, as part of a population-based cohort study. Pregnant women without a diagnosis of depression participated, who were divided into two groups: risk of depression (CBT) and a control group (without therapy). The preventive therapy consisted of six sessions of CBT, administered weekly. The Outcome Questionnaire (OQ-45) was used in all sessions. The Mini International Neuropsychiatric Interview and Beck Depression Inventory-II were used on three occasions. The final statistical analyses were performed by Poisson regression.

Results: The prevalence of PPD in the risk group was 5.5% and in the control group 2.2%, with no difference between the groups (PR 1.66 95% CI 0.44-6.18). The OQ-45 averages gradually reduced during the therapy sessions, indicating therapeutic progress. Schooling was an associated factor, both with the manifestation of PPD and with the greater effectiveness of the therapy.

Limitations: Rate of 40.5% refusal to preventive treatment and absence of a group with similar characteristics in another therapy model.

Conclusions: Brief cognitive behavioral therapy applied by mental health professionals with basic training was effective in preventing the manifestation of PPD.
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http://dx.doi.org/10.1016/j.jad.2021.04.031DOI Listing
April 2021

Maternal-fetal attachment and perceived parental bonds of pregnant women.

Early Hum Dev 2021 Mar 22;154:105310. Epub 2021 Jan 22.

Postgraduate Program in Health and Behavior, Catholic University of Pelotas (UCPel), Gonçalves Chaves, 373 - 411 C, 96015-560 Pelotas, RS, Brazil. Electronic address:

Background: The parental bond is characterized by the perception of care and protection received by parental figures throughout human development. During the gestational period, the intensity in which the woman manifests behaviors and feelings for the fetus was denominated maternal-fetal attachment (MFA). In this perspective, the literature indicates that there is association between MFA and the pregnant woman's perception about the bond established with her parents.

Aims: This study aimed to evaluate the association between MFA and perceived parental bonds of pregnant women in the city of Pelotas/RS (Brazil).

Study Design: This is a cohort study with 839 women during their gestational period. All women answered to the Parental Bonding Instrument to investigate the perceived parental bonds, and the MFA was assessed through the Maternal-Fetal Attachment Scale.

Results: The main results showed that perceived paternal overprotection was associated with a higher MFA after adjustment (B 2.00 CI95% 0.30; 3.70). Additionally, the pregnant women who were in the first trimester of pregnancy (p < 0.001), who did not live with a partner (p = 0.018), and who did not feel supported by the baby's father during pregnancy (p = 0.014) presented lower scores of MFA.

Conclusion: This study showed the importance of the paternal role in the women's life, considering the perception of the bond with their father during their development, an adequate support by the father of the baby, and the presence of a partner during pregnancy. As a result, the paternal role may influence the feelings and behaviors of greater affection, care, and concern regarding the fetus.
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http://dx.doi.org/10.1016/j.earlhumdev.2021.105310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910275PMC
March 2021

BDNF Val66Met polymorphism and resilience in major depressive disorder: the impact of cognitive psychotherapy.

Braz J Psychiatry 2020 1;43(1):22-28. Epub 2021 Feb 1.

Programa de Pós-Graduação em Saúde e Comportamento (PPGSC), Universidade Católica de Pelotas (UCPel), Pelotas, RS, Brazil.

Objective: Clinical and biological correlates of resilience in major depressive disorder are scarce. We aimed to investigate the effect of the Val66Met polymorphism in the BDNF gene on resilience scores in major depressive disorder patients and evaluate the polymorphism's moderation effect on resilience scores in response to cognitive therapy.

Method: A total of 106 major depressive disorder patients were enrolled in this clinical randomized study. The Resilience Scale and the Hamilton Rating Scale for Depression were applied at baseline, post-treatment, and at six months of follow-up. Blood samples were obtained at baseline for molecular analysis.

Results: The baseline resilience scores were higher in patients with the Met allele (114.6±17.6) than in those with the Val/Val genotype (104.04±21.05; p = 0.037). Cognitive therapy treatment increased resilience scores (p ≤ 0.001) and decreased depressive symptoms (p ≤ 0.001). In the mixed-effect model, the Val/Val genotype represented a decrease in resilience scores (t218 = -1.98; p = 0.048), and the Val66Met polymorphism interacted with sex to predict an increase in total resilience scores during cognitive treatment (t218 = 2.69; p = 0.008).

Conclusion: Our results indicate that cognitive therapy intervention could improve resilience in follow-up, considering that gender and genetic susceptibility are predicted by the Val66Met polymorphism.
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http://dx.doi.org/10.1590/1516-4446-2019-0726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861181PMC
February 2021

Generalized Anxiety Disorder, Depressive Symptoms and the Occurrence of Stressors Events in a Probabilistic Sample of Pregnant Women.

Psychiatr Q 2021 Mar;92(1):123-133

Postgraduate Program in Health and Behavior, Catholic University of Pelotas (UCPel), Gonçalves Chaves, 377 - 411 C - 96015-560, Pelotas, RS, Brazil.

The aim of the study is to verify the association between GAD, the severity of depressive symptoms and stressors in pregnant women between the first and second trimester. Cross-sectional study, part of a cohort that followed 980 women during the gestational period of a city in southern Brazil. We performed bivariate analysis using the t-test and chi-square. The variables that presented p ≤ 0.20 were taken for multivariate analysis, through logistic regression, in order to control possible confounding factors. The Mini International Neuropsychiatric Interview Plus was used to evaluate GAD, the severity of depressive symptoms was investigated through the Beck Inventory of Depression II, and stress events according to the Social Readjustment Assessment Scale of Holmes e Rahe. The sample consisted of 980 women. Women with mild depression symptoms had 9.8 (IC95% 4.6;21.0) times more GAD, those with moderate symptoms had 27.5 (IC95% 12.5;60.0) times more GAD, and those with severe symptoms had 52.9 (IC95% 19.1;146.5) times more GAD when compared to pregnant women with no symptoms or minimal symptoms. Regarding the stressful events, the pregnant women who presented GAD had an increase of 1.0 (IC95% 1.0;1.1) point in the mean of occurrence of stressor events when compared to those without GAD. These findings highlight the need for prevention strategies and interventions to promote maternal mental health, which benefit the development of infants in the long term.
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http://dx.doi.org/10.1007/s11126-020-09763-0DOI Listing
March 2021

Temperament traits moderate the relationship between Childhood Trauma and Interleukin 1β profile in young adults.

Psychoneuroendocrinology 2020 06 16;116:104671. Epub 2020 Apr 16.

Programa de Pós-Graduação em Saúde e Comportamento, Universidade Católica de Pelotas, Pelotas, Brazil. Electronic address:

Early life stressors, such as childhood trauma, have been associated to alterations in immune response that can last until adulthood. In this context, interleukin 1β (IL-1β) emerges as a pro-inflammatory cytokine with a pivotal role. Also, considering the temperament differences in stress susceptibility, and even immune dysfunction, studies investigating the complex interaction between these factors are scarce. Thus, the aim of the present study was to evaluate the moderating role of temperament traits in the relationship between childhood trauma and serum IL-1β levels. This cross-sectional study consisted of 325 individuals, men and women, aged 18-35, enrolled from a population-based study in the city of Pelotas, Southern Brazil. Our main results indicate that higher serum levels of IL-1β were associated with trauma severity (p < 0.01), and the variance of anger could explain 29% of IL-1β increase in individuals who suffered severe trauma (p < 0.05). The effect of anger was considerably stronger in men than in women (46% and 25%, respectively). Moreover, the variance of sensitivity also explained 15% of IL-1β increase (p < 0.05) as well as the variance of volition explained 11% of IL-1β decrease (p < 0.05) in individuals who suffered severe trauma in the general population. Our results indicate that emotional individual differences can moderate the impact of childhood trauma on low-grade inflammation in young adults.
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http://dx.doi.org/10.1016/j.psyneuen.2020.104671DOI Listing
June 2020

The role of CACNA1C gene and childhood trauma interaction on bipolar disorder.

Prog Neuropsychopharmacol Biol Psychiatry 2020 07 10;101:109915. Epub 2020 Mar 10.

Laboratory of Clinical Neuroscience, Post-graduation Program in Health and Behavior, Catholic University of Pelotas, Pelotas, Rio Grande do Sul, Brazil. Electronic address:

Studies on gene x environment interaction (GxE) have provided vital information for uncovering the origins of complex diseases. When considering the etiology of bipolar disorder (BD), the role of such interactions is unknown. Here, we tested whether trauma during childhood could modify the effect of two polymorphisms in the CACNA1C gene (rs1006737 and rs4765913) in terms of susceptibility to BD. The study enrolled 878 Caucasian young adults in a cross-sectional population-based survey. BD diagnosis was performed using a clinical interview MINI 5.0, and trauma was assessed with the childhood trauma questionnaire (CTQ). Binary logistic regression models were employed to test the main effects of polymorphisms, haplotypes, and GxE interactions using sex as a confounder. We did not observe an association between the polymorphisms and diagnosis of BD. However, we noted that childhood trauma modified the effect of the rs4765913 polymorphism (p = .018) and the AA haplotype (rs1006737 - rs4765913) (p = .018) on BD susceptibility. A allele carriers of the rs4765913 polymorphism or the AA haplotype exposed to childhood trauma are more likely to develop BD compared to the individuals without a genetic risk. Thus, this study showed that the risk of developing BD in individuals exposed to childhood trauma was influenced by the individual's genetic background, varying according to the CACNA1C genotypes.
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http://dx.doi.org/10.1016/j.pnpbp.2020.109915DOI Listing
July 2020

CD300f immunoreceptor is associated with major depressive disorder and decreased microglial metabolic fitness.

Proc Natl Acad Sci U S A 2020 03 9;117(12):6651-6662. Epub 2020 Mar 9.

Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, 11400 Montevideo, Uruguay;

A role for microglia in neuropsychiatric diseases, including major depressive disorder (MDD), has been postulated. Regulation of microglial phenotype by immune receptors has become a central topic in many neurological conditions. We explored preclinical and clinical evidence for the role of the CD300f immune receptor in the fine regulation of microglial phenotype and its contribution to MDD. We found that a prevalent nonsynonymous single-nucleotide polymorphism (C/T, rs2034310) of the human CD300f receptor cytoplasmic tail inhibits the protein kinase C phosphorylation of a threonine and is associated with protection against MDD, mainly in women. Interestingly, CD300f mice displayed several characteristic MDD traits such as augmented microglial numbers, increased interleukin 6 and interleukin 1 receptor antagonist messenger RNA, alterations in synaptic strength, and noradrenaline-dependent and persistent depressive-like and anhedonic behaviors in females. This behavioral phenotype could be potentiated inducing the lipopolysaccharide depression model. RNA sequencing and biochemical studies revealed an association with impaired microglial metabolic fitness. In conclusion, we report a clear association that links the function of the CD300f immune receptor with MDD in humans, depressive-like and anhedonic behaviors in female mice, and altered microglial metabolic reprogramming.
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http://dx.doi.org/10.1073/pnas.1911816117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104369PMC
March 2020

The T102C polymorphism of 5HT2A receptor in oral epithelial dysplasia: A pilot case-control study.

Arch Oral Biol 2020 May 24;113:104688. Epub 2020 Feb 24.

Graduate Program in Health and Behavior, Catholic University of Pelotas, Pelotas, RS, 96010-901, Brazil. Electronic address:

Objective: investigate the T102C polymorphism of 5HT2A receptor in dysplasia in oral potentially malignant lesions and its association with smoking and alcohol habits.

Methods: case-control study that included patients with oral potentially malignant lesions (OPML) histopathologically diagnosed with dysplasia and healthy controls, and within these group patients with and without smoking and alcohol consumption habits. Cell samples from the oral lesions were collected with the patients previously anesthetized using disposable cytological brushes. Deoxyribonucleic acid (DNA) extraction was performed and the T102C polymorphism (rs6313) was genotyped in a real-time polymerase chain reaction (PCR) allelic discrimination assays.

Results: 110 individuals were included in this study (38 with dysplasia and 72 controls). The genotype (p = 0.016), allele (p = 0.020) and smoking habits (<0.001) distribution differed significantly between dysplasia and control group, where the CT and TT (C - cytosine/ T - thymine) genotype and the T allele showed a higher frequency in dysplasia (65.6, 18.8 and 84.4 %, respectively) than in controls (55.7, 4.9 and 60.7). Concerning smoking habits, the higher frequency was in the dysplasia group. The multivariate logistic regression analysis, associating variables of interest and the presence of dysplasia, showed that individuals with smoking habits present 7.58 increase risk to develop dysplasia than non-smokers; and individuals carrying the T allele for the T102C polymorphism have a 4.6 increased risk to develop oral dysplasia in OPML.

Conclusions: the T102C polymorphism is associated with oral dysplasia in OPML, however, failed to show association with smoking and alcohol habits in OPML dysplasia.
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http://dx.doi.org/10.1016/j.archoralbio.2020.104688DOI Listing
May 2020

Inosine prevents hyperlocomotion in a ketamine-induced model of mania in rats.

Brain Res 2020 04 8;1733:146721. Epub 2020 Feb 8.

Postgraduate Program in Health and Behavior, Catholic University of Pelotas, Rio Grande do Sul, Brazil. Electronic address:

Bipolar Disorder is a disorder characterized by alternating episodes of depression, mania or hypomania, or even mixed episodes. The treatment consists on the use of mood stabilizers, which imply serious adverse effects. Therefore, it is necessary to identify new therapeutic targets to prevent or avoid new episodes. Evidence shows that individuals in manic episodes present a purinergic system dysfunction. In this scenario, inosine is a purine nucleoside known to act as an agonist of A and A adenosine receptors. Thus, we aimed to elucidate the preventive effect of inosine on locomotor activity, changes in purine levels, and adenosine receptors density in a ketamine-induced model of mania in rats. Inosine pretreatment (25 mg/kg, oral route) prevented the hyperlocomotion induced by ketamine (25 mg/kg, intraperitoneal route) in the open-field test; however, there was no difference in hippocampal density of A and A receptors, where ketamine, as well as inosine, were not able to promote changes in immunocontent of the adenosine receptors. Likewise, no effects of inosine pretreatments or ketamine treatment were observed for purine and metabolic residue levels evaluated. In this sense, we suggest further investigation of signaling pathways involving purinergic receptors, using pharmacological strategies to better elucidate the action mechanisms of inosine on bipolar disorder. Despite the limitations, inosine administration could be a promising candidate for bipolar disorder treatment, especially by attenuating maniac phase symptoms, once it was able to prevent the hyperlocomotion induced by ketamine in rats.
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http://dx.doi.org/10.1016/j.brainres.2020.146721DOI Listing
April 2020

Evaluation of cytological diagnostic accuracy for canine splenic neoplasms: An investigation in 78 cases using STARD guidelines.

PLoS One 2019 7;14(11):e0224945. Epub 2019 Nov 7.

Diagnostic Pathology Service, Dipartimento di Medicina Veterinaria (DIMEVET), Università degli Studi di Milano, Lodi, Italy.

Cytology represents a useful diagnostic tool in the preliminary clinical approach to canine splenic lesions, and may prevent unnecessary splenectomy. However, few studies have evaluated diagnostic accuracy of cytology in the diagnosis of canine splenic neoplasms. The aim of this study was to determine overall accuracy, sensitivity, specificity, positive and negative predictive values (i.e. diagnostic accuracy indexes) of cytology for canine splenic neoplasms following Standards for the Reporting of Diagnostic Accuracy Studies (STARD) guidelines. A consecutive series of canine splenic cytological samples was retrospectively retrieved from the database of the Diagnostic Pathology Service of the Department of Veterinary Medicine (DIMEVET-University of Milan). Histopathology was set as the diagnostic reference standard. Cytological cases were enrolled when slides were available for review and when the same lesion was submitted for histopathology. Seventy-eight (78) lesions were included in the study. By histopathology, 56 were neoplastic and 22 were non-neoplastic. Cytology had an overall accuracy of 73.08% (95% C.I. 61.84%-82.50%), sensitivity of 64.29% (95% C.I. 50.36%-76.64%), specificity of 95.45% (95% C.I. 77.16%-99.88%), and positive and negative predictive values of 97.3% (95% C.I. 84.01%-99.60%) and 51.22% (95% C.I. 42.21%-60.15%), respectively. Low sensitivity and negative predictive value were balanced by very high specificity and positive predictive value. When positive for neoplasia, cytology represents a useful diagnostic tool to rule in splenic neoplasia, prompting surgery independently from other diagnostic tests. Conversely, a negative cytological result requires additional investigations to confirm the dog to be disease free.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224945PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837434PMC
March 2020

The Role of in Shared Susceptibility of Psychiatric Disorders during Childhood: A Population-Based Birth Cohort Study.

Genes (Basel) 2019 08 20;10(8). Epub 2019 Aug 20.

Departamento de Medicina Preventiva, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brasil.

Background: It has been suggested that microRNAs (miRNAs; short non-protein-coding RNA molecules that mediate post-transcriptional regulation), including mir-9 and mir-34 families, are important for brain development. Current data suggest that mir-9 and mir-34 may have shared effects across psychiatric disorders. This study aims to explore the role of genetic polymorphisms in the (rs4916723) and (rs4938723) genes on the susceptibility of psychiatric disorders in children from the 2004 Pelotas Birth Cohort.

Methods: Psychiatric disorders were assessed in 3585 individuals using Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), criteria through the application of standard semi-structured interviews (using the Development and Well-Being Assessment, DAWBA) at the six-years-of-age follow-up. The outcome was defined as the presence of any mental disorder. We also considered two broad groups of internalizing and externalizing disorders to further investigate the role of these variants in mental health.

Results: We observed an association between rs4916723 () and the presence of any psychiatric disorder (odds ratios (OR) = 0.820; 95% CI = 0.7130-0.944; = 0.006) and a suggestive effect on internalizing disorders (OR = 0.830; 95% CI = 0.698-0.987; = 0.035). rs4938723 () was not associated with any evaluated outcome.

Conclusion: The study suggests that may have an important role on a broad susceptibility for psychiatric disorders and may be important mainly for internalization problems.
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http://dx.doi.org/10.3390/genes10080626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723948PMC
August 2019

Leptin polymorphism rs3828942: risk for anxiety disorders?

Eur Arch Psychiatry Clin Neurosci 2019 Aug 16. Epub 2019 Aug 16.

Institute of Health Sciences, Department of Health and Behavior, Catholic University of Pelotas - UCPel, Rua Gonçalves Chaves 373, Sala 324, Pelotas, RS, 96010-280, Brazil.

Leptin is an anorexigenic hormone well recognized by its role in mediating energy homeostasis. Recently, leptin has been associated with psychiatric disorders and interestingly, leptin treatment has shown antidepressant and anxiolytic effects. We examined the association of leptin levels and leptin (LEP) gene rs3828942 polymorphism with anxiety disorders considering sex differences. A cross-sectional population-based study, including 1067 young adults, of whom 291 presented anxiety disorders diagnosed by the Mini International Neuropsychiatric Interview (MINI 5.0). The rs3828942 polymorphism was genotyped by real-time PCR and ELISA measured leptin levels. Leptin levels were not associated with anxiety disorders after adjusting for sex and body mass index (BMI) [ß = - 0.009 (- 0.090-0.072); p = 0.832]. The distribution of rs3828942 genotypes was not associated with anxiety disorders. However, in a sex-stratified sample, the A-allele of rs3828942 polymorphism was associated with risk for GAD in women even when adjusting for confounding variables [OR = 1.87 (1.17-2.98); p = 0.008]. In a subsample of 202 individuals with GAD and control matched by sex and BMI, results suggest an interaction between genotypes and GAD diagnosis based on leptin levels only in the male group [F (1, 54) = 6.464; p = 0.0139]. Leptin is suggested to be related with the neurobiology of anxiety disorders in a sex-dependent manner since women carrying the A-allele of LEP rs3828942 present a higher risk for GAD, while leptin levels seem to be lower in men with GAD carrying A-allele. Studies on the relationship between leptin polymorphisms and levels are scarce and, therefore, further research is necessary.
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http://dx.doi.org/10.1007/s00406-019-01051-8DOI Listing
August 2019

MicroRNAs expressed in depression and their associated pathways: A systematic review and a bioinformatics analysis.

J Chem Neuroanat 2019 10 22;100:101650. Epub 2019 May 22.

Depression is a debilitating mental illness, one of the most prevalent worldwide. MicroRNAs have been studied to better understand the biological mechanisms that regulate this disease. This study review systematically the literature to identify which microRNAs are currently being associated with depression and their related pathways. The electronic search was conducted in PubMed, Scopus, Scielo, ISI Web of Knowledge, and PsycINFO databases, using the search terms "Depressive Disorder" or "Depression" and "MicroRNAs". After, microRNAs that were up and down-regulated in depression were analyzed by bioinformatics. We observed that among the 77 microRNAs cited by included studies, 54 had their levels altered in depressed individuals compared to controls, 30 being up-regulated and 24 down-regulated. The bioinformatics analysis revealed that among the up-regulated microRNAs there were 81 total and 43 union pathways, with 15 presenting a significant difference. Among the down-regulated microRNAs, 67 total and 45 union pathways were found, with 14 presenting a significant difference. The miR-17-5p and let-7a-5p were the most frequently found microRNAs in the statistically significant pathways. In this study a panel of altered microRNAs in depression was created with their related pathways, which is a step towards understanding the complex network of microRNAs in depression.
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http://dx.doi.org/10.1016/j.jchemneu.2019.101650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996133PMC
October 2019

Persistent organic pollutants in fish: biomonitoring and cocktail effect with implications for food safety.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2019 Apr 12;36(4):601-611. Epub 2019 Mar 12.

b DIMEVET-Department of Veterinary Medicine , School of Veterinary Medicine , Milano , Italy.

The impact of anthropogenic wastes of persistent organic pollutants (POPs) on the marine environment has increased in the last decades. POPs include polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCs). To assess the levels of these POPs in the wild fish population, pelagic and benthopelagic predator fish species were selected as biomonitors. For detection and quantification of POPs in muscular tissues, a simple extraction through Accelerated-Solvent-Extraction (ASE) with an 'in-line' clean up purification approach was applied, followed by a GC-MS/MS analysis. Concentrations of sum DDT, sum HCH and endrin correlated with all PCB concentrations. Significant differences among fish species were found for all OCs and all PCBs except PCB 31 and 101. Blackspot seabream had the highest PCB concentrations; OCs were highest in tuna. Due to major concerns regarding fish population losses and the possible human chronic exposure to contaminated fish, studies addressing combined effects of multiple POPs ('cocktail effect') should be implemented. Our data motivate further experimental and observational studies in fish to define adequate baseline levels for cumulative human exposure and potential role of these contaminants for food safety.
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http://dx.doi.org/10.1080/19440049.2019.1579926DOI Listing
April 2019

Impact of genetic variations in ADORA2A gene on depression and symptoms: a cross-sectional population-based study.

Purinergic Signal 2019 03 3;15(1):37-44. Epub 2018 Dec 3.

Department of Life and Health Sciences, Catholic University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.

Genetic variants involved in adenosine metabolism and its receptors were associated with increased risk for psychiatric disorders, including anxiety, depression, and schizophrenia. Here, we examined an association between a single nucleotide polymorphism in A receptor gene (ADORA2A, rs2298383 SNP) with current depressive episode and symptom profile. A total of 1253 individuals from a cross-sectional population-based study were analyzed by the Mini International Neuropsychiatric Interview 5.0. Our data showed that the TT genotype of ADORA2A rs2298383 SNP was associated with reduced risk for depression when compared to the CC/CT genotypes (p = 0.020). This association remained significant after adjusting for confounding variables such as smoking, gender, socioeconomic class, and ethnicity (OR = 0.631 (95% CI 0.425-0.937); p = 0.022). Regarding the symptoms associated with depression, we evaluated the impact of the ADORA2A SNP in the occurrence of sad/discouraged mood, anhedonia, appetite changes, sleep disturbances, motion changes, energy loss, feelings of worthless or guilty, difficulty in concentrating, and presence of bad thoughts. Notably, the TT genotype was independently associated with reduced sleep disturbances (OR = 0.438 (95% CI 0.258-0.743); p = 0.002) and less difficulty in concentrating (OR = 0.534 (95% CI 0.316-0.901; p = 0.019). The cross-sectional design cannot evaluate the cause-effect relationship and did not evaluate the functional consequences of this polymorphism. Our data support an important role for ADORA2A rs2298383 SNP in clinical heterogeneity associated with depression. The presence of the TT genotype was associated with decrease risk for current depression and disturbances in sleep and attention, two of the most common symptoms associated with this disorder.
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http://dx.doi.org/10.1007/s11302-018-9635-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439088PMC
March 2019

Iodonium salt incorporation in dental adhesives and its relation with degree of conversion, ultimate tensile strength, cell viability, and oxidative stress.

Clin Oral Investig 2019 Mar 1;23(3):1143-1151. Epub 2018 Jul 1.

Post-Graduate Program in Health and Behavior, Catholic University of Pelotas, Rua Félix da Cunha, 412, Cep., Pelotas, RS, 96010-901, Brazil.

Objective: The aim of this study was to evaluate the degree of conversion, ultimate tensile strength, cell viability, and oxidative stress of two different ternary initiation systems, using two photoinitiation polymerization times.

Methods: The groups investigated were camphorquinone (CQ); CQ and diphenyleneiodonium hexafluorophosphate (DPI); CQ and ethyl 4-dimethylamine benzoate (EDAB); and CQ, EDAB, and DPI, with EDAB in high and low concentration. To assess the degree of conversion (DC) and the ultimate tensile strength (UTS), a real-time Fourier transform infrared spectroscopy and a universal test machine Emic DL-500 were used, respectively. Cell viability and oxidative stress were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), superoxide dismutase (SOD), total sulfhydryl (SH) content, and thiobarbituric acid reactive species (TBARS) formation assays.

Results: Slight lower cell viability was shown when DPI was associated with high concentrations of EDAB; this reduction seemed to be attenuated when lower concentrations of EDAB were used. When EDAB and DPI were associated, no oxidative damage was shown. The degree of conversion was increased in the ternary systems (CQ + EDAB lower concentration + DPI) group, which did not affect the UTS, cytotoxicity, and oxidative stress parameters. The polymerization time did not affect cell viability, total SH, and TBARS; however, a slight increase was shown in SOD levels.

Clinical Relevance: Our study emphasizes the relevance of incorporating the third element-iodonium salt-in a binary adhesive systems composed exclusively of CQ and EDAB.
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http://dx.doi.org/10.1007/s00784-018-2527-6DOI Listing
March 2019

Effects of cognitive-behavioral therapy on neurotrophic factors in patients with major depressive disorder.

Braz J Psychiatry 2018 Oct-Dec;40(4):361-366. Epub 2018 Jun 11.

Departamento de Saúde e Comportamento, Universidade Católica de Pelotas, Pelotas, RS, Brazil.

Objective: To correlate neurotrophic factors - brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and beta-nerve growth factor (beta-NGF) - and severity of depressive symptoms in patients diagnosed with major depressive disorder (MDD) undergoing cognitive-behavioral therapy (CBT).

Methods: In this quasi-experimental study, participants were selected by convenience and received 16 sessions of CBT. The outcomes of interest were severity of depressive symptoms and changes in neurotrophic factor levels after CBT. The differences between variables before and after treatment (deltas) were analyzed.

Results: Patients had significant changes in symptom severity after treatment. No significant associations were found between Beck Depression Inventory II (BDI-II) scores and any independent variable. No correlations were observed between BDNF or GDNF levels and BDI scores before or after treatment, although there was a trend toward significant differences in beta-NGF levels.

Conclusion: BDNF, beta-NGF, and GDNF were not influenced by the effects of CBT on depressive symptoms.
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http://dx.doi.org/10.1590/1516-4446-2017-2357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899377PMC
September 2018

Depression and peripheral inflammatory profile of patients with obesity.

Psychoneuroendocrinology 2018 05 9;91:132-141. Epub 2018 Mar 9.

Department of Biochemistry, Federal University of Santa Catarina Florianópolis, Santa Catarina, Brazil. Electronic address:

This narrative review will present and discuss clinical data from 16 cross-sectional and 6 longitudinal studies examining the relationship between body mass index (BMI), symptoms of depression and peripheral inflammation. Our aim is to determine which of obesity and depression contributes best to the peripheral low-grade inflammation frequently associated to both conditions. Studies including a complete evaluation of inflammatory markers are scarce and high levels of interleukin-6 (IL-6) and C-reactive protein (CRP) are the most consistent findings associated with obesity and symptoms of depression. Among the cross-sectional studies, seven studies, including a total of 9421 individuals, pointed to BMI as the major factor associated with systemic low-grade inflammation. However, in four studies, including 16,837 individuals, CRP levels remained associated with the symptoms of depression even after correction for BMI, suggestion that in the absence of overweight or obesity other sources of peripheral inflammation might contribute to presence of depressive symptoms. Additionally, another five studies, including 5569 individuals failed to find an association between depression and peripheral inflammation, reinforcing the heterogeneity of this condition. In the longitudinal data, changes in BMI were associated with a reduction in depressive scores at follow-up, after bariatric surgery or after diet. In four longitudinal studies, high levels of CRP were found to be associated with depression even after adjustment for BMI and weight loss, further corroborating the idea that other sources of peripheral inflammation might contribute to depressive symptoms. Thus it seems that both obesity and depressive symptoms can contribute to peripheral inflammation, and once installed the presence of inflammation can contribute to several behavioral alterations that reinforce the cyclic pattern of co-occurrence observed in patients with obesity and MDD. Future clinical studies should focus on strategic efforts to collect new data and to improve or standardize methods for the evaluation of depression, body composition and a more complete inflammatory profile. These approaches are essential for the development of pharmacological and/or non-pharmacological strategies designed to break this cyclic pattern of co-occurrence.
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http://dx.doi.org/10.1016/j.psyneuen.2018.03.005DOI Listing
May 2018

The role of CLOCK gene in psychiatric disorders: Evidence from human and animal research.

Am J Med Genet B Neuropsychiatr Genet 2018 03 13;177(2):181-198. Epub 2017 Sep 13.

Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil.

The circadian clock system drives daily rhythms in physiology, metabolism, and behavior in mammals. Molecular mechanisms of this system consist of multiple clock genes, with Circadian Locomotor Output Cycles Kaput (CLOCK) as a core member that plays an important role in a wide range of behaviors. Alterations in the CLOCK gene are associated with common psychiatric disorders as well as with circadian disturbances comorbidities. This review addresses animal, molecular, and genetic studies evaluating the role of the CLOCK gene on many psychiatric conditions, namely autism spectrum disorder, schizophrenia, attention-deficit/hyperactivity disorder, major depressive disorder, bipolar disorder, anxiety disorder, and substance use disorder. Many animal experiments focusing on the effects of the Clock gene in behavior related to psychiatric conditions have shown consistent biological plausibility and promising findings. In humans, genetic and gene expression studies regarding disorder susceptibility, sleep disturbances related comorbidities, and response to pharmacological treatment, in general, are in agreement with animal studies. However, the number of controversial results is high. Literature suggests that the CLOCK gene exerts important influence on these conditions, and influences the susceptibility to phenotypes of psychiatric disorders.
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http://dx.doi.org/10.1002/ajmg.b.32599DOI Listing
March 2018

NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings.

Brain Behav Immun 2017 Aug 2;64:367-383. Epub 2017 Mar 2.

Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil. Electronic address:

Over the past three decades, an intricate interaction between immune activation, release of pro-inflammatory cytokines and changes in brain circuits related to mood and behavior has been described. Despite extensive efforts, questions regarding when inflammation becomes detrimental or how we can target the immune system to develop new therapeutic strategies for the treatment of psychiatric disorders remain unresolved. In this context, novel aspects of the neuroinflammatory process activated in response to stressful challenges have recently been documented in major depressive disorder (MDD). The Nod-like receptor pyrin containing 3 inflammasome (NLRP3) is an intracellular multiprotein complex responsible for a number of innate immune processes associated with infection, inflammation and autoimmunity. Recent data have demonstrated that NLRP3 activation appears to bridge the gap between immune activation and metabolic danger signals or stress exposure, which are key factors in the pathogenesis of psychiatric disorders. In this review, we discuss both preclinical and clinical evidence that links the assembly of the NLRP3 complex and the subsequent proteolysis and release of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) in chronic stress models and patients with MDD. Importantly, we also focus on the therapeutic potential of targeting the NLRP3 inflammasome complex to improve stress resilience and depressive symptoms.
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http://dx.doi.org/10.1016/j.bbi.2017.03.002DOI Listing
August 2017

NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings.

Brain Behav Immun 2017 Aug 2;64:367-383. Epub 2017 Mar 2.

Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil. Electronic address:

Over the past three decades, an intricate interaction between immune activation, release of pro-inflammatory cytokines and changes in brain circuits related to mood and behavior has been described. Despite extensive efforts, questions regarding when inflammation becomes detrimental or how we can target the immune system to develop new therapeutic strategies for the treatment of psychiatric disorders remain unresolved. In this context, novel aspects of the neuroinflammatory process activated in response to stressful challenges have recently been documented in major depressive disorder (MDD). The Nod-like receptor pyrin containing 3 inflammasome (NLRP3) is an intracellular multiprotein complex responsible for a number of innate immune processes associated with infection, inflammation and autoimmunity. Recent data have demonstrated that NLRP3 activation appears to bridge the gap between immune activation and metabolic danger signals or stress exposure, which are key factors in the pathogenesis of psychiatric disorders. In this review, we discuss both preclinical and clinical evidence that links the assembly of the NLRP3 complex and the subsequent proteolysis and release of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) in chronic stress models and patients with MDD. Importantly, we also focus on the therapeutic potential of targeting the NLRP3 inflammasome complex to improve stress resilience and depressive symptoms.
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http://dx.doi.org/10.1016/j.bbi.2017.03.002DOI Listing
August 2017

Preventive effects of blueberry extract on behavioral and biochemical dysfunctions in rats submitted to a model of manic behavior induced by ketamine.

Brain Res Bull 2016 10 18;127:260-269. Epub 2016 Oct 18.

Programa de Pós Graduação em Bioquímica e Bioprospecção, Laboratório de Neuroquímica, Inflamação e Câncer, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário S/N, Pelotas, RS, Brazil. Electronic address:

The aim of the present study was to evaluate the protective effects of blueberry extract on oxidative stress and inflammatory parameters in a model of mania induced by ketamine administration in rats. Male rats were pretreated with blueberry extract (200mg/kg, once a day for 14days), lithium chloride (45mg/kg, mood stabilizer used as a positive control, twice a day for 14days), or vehicle. Between the 8th and 14th days, rats also received an injection of ketamine (25mg/kg) or vehicle. In the 15th day, thirty minutes after ketamine administration the hyperlocomotion of the animals was assessed in the open - field apparatus. Immediately after the behavioral analysis brain and blood were collected for biochemical determinations. ketamine treatment induced hyperlocomotion and oxidative damage in cerebral cortex, hippocampus and striatum such as an increase in lipid peroxidation and a decrease in the antioxidant enzymes activities (superoxide dismutase, catalase e glutatione peroxidase). Ketamine administration also increased the IL-6 levels in serum in rats. Pretreatment of rats with blueberry extract or lithium prevented the hyperlocomotion, pro - oxidant effects and inflammation induced by ketamine. Our findings suggest that blueberry consumption has a neuroprotective potential against behavioral and biochemical dysfunctions induced in a preclinical model that mimic some aspects of the manic behavior.
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http://dx.doi.org/10.1016/j.brainresbull.2016.10.008DOI Listing
October 2016

Curcumin in depressive disorders: An overview of potential mechanisms, preclinical and clinical findings.

Eur J Pharmacol 2016 Aug 24;784:192-8. Epub 2016 May 24.

Programa de Pós-Graduação em Saúde e Comportamento - Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brasil. Electronic address:

Considering the high prevalence of psychiatric disorders, its social burden and the limitations of currently available treatments, alternative therapeutic approaches targeting different biological pathways have been investigated. Curcumin is a natural compound with multi-faceted pharmacological properties, interacting with several neurotransmitter systems and intracellular signaling pathways involved in mood regulation. Also, curcumin has anti-inflammatory, antioxidant and neurotrophic effects, suggesting a strong potential to manage conditions associated with neurodegeneration, such as psychiatric disorders. Most literature data focused on the potential of curcumin to counteract behavioral and neurochemical alterations in preclinical models of depression. The findings still need to be further explored and clinical reports share some controversial results that might be associated with its low systemic bioavailability following oral administration. Other psychiatric disorders also have neurochemical alterations similar to those found in depression, including neurotoxicity, oxidative stress and neuroinflammation. Despite the limited number of reports, preclinical models investigated the potential role for curcumin in anxiety, bipolar disorder, post-traumatic stress disorder and autism spectrum disorders. Here, we will summarize the cellular targets of curcumin relevant to psychiatric disorders and its effects in preclinical and clinical studies with depression, anxiety disorders and other psychiatric related conditions.
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http://dx.doi.org/10.1016/j.ejphar.2016.05.026DOI Listing
August 2016

Intra-abdominal fluid aspirate from a dog.

Diagn Cytopathol 2016 Feb 15;44(2):119-20. Epub 2015 Dec 15.

Dipartimento di Patologia Animale, Igiene e Sanità Pubblica Veterinaria - Sezione Di Anatomia Patologica Veterinaria e Patologia Aviare, Università Degli Studi Di Milano, Milano, Italy.

A 12-year-old, neutered female, Siberian husky, was presented with a 6-months history of progressive abdominal distension, anorexia, and weight loss. The dog appeared normal on physical examination except for marked abdominal distension. A fluid wave was balloted strongly suggesting an abdominal effusion. Ultrasound examination confirmed this clinical finding. Results of the CBC included mild nonregenerative anemia, with an RBC count of 4.9 × 10(6)/µL (reference interval 5.5-8.5 × 10(6)/µL), hemoglobin concentration of 12 g/dL (reference interval 12-18 g/dL), HCT of 36% (reference interval 37-55%), and reticulocytes <60,000/µL. No abnormalities in serum chemistry were detected.
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http://dx.doi.org/10.1002/dc.23405DOI Listing
February 2016

Association of interleukin-10 levels with age of onset and duration of illness in patients with major depressive disorder.

Braz J Psychiatry 2015 Oct-Dec;37(4):296-302. Epub 2015 Sep 29.

Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, RS, Brazil.

Objective: To investigate peripheral levels of interleukin-10 (IL-10) in patients with major depressive disorder (MDD) and bipolar disorder (BD) and evaluate the relationship between IL-10, age of disease onset, and duration of illness.

Methods: Case-control study nested in a population-based cohort of 231 individuals (age 18-24 years) living in Pelotas, state of Rio Grande do Sul, Brazil. Participants were screened for psychopathology using the Mini-International Neuropsychiatric Interview (MINI) and the Structured Clinical Interview for DSM-IV (SCID-I). Serum IL-10 was measured using commercially available immunoassay kits.

Results: Peripheral levels of IL-10 were not significantly different in individuals with MDD or BD as compared to controls. However, higher IL-10 levels were found in MDD patients with a later disease onset as compared with controls or early-onset patients. In addition, IL-10 levels correlated negatively with illness duration in the MDD group. In the BD group, age of onset and duration of illness did not correlate with IL-10 levels.

Conclusion: Higher levels of IL-10 are correlated with late onset of MDD symptoms. Moreover, levels of this cytokine might decrease with disease progression, suggesting that an anti-inflammatory balance may be involved in the onset of depressive symptoms and disease progression in susceptible individuals.
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http://dx.doi.org/10.1590/1516-4446-2014-1452DOI Listing
May 2016

Elodontoma in Two Guinea Pigs.

J Vet Dent 2015 ;32(2):111-9

Elodontoma was diagnosed in two pet guinea pigs, one involving a maxillary premolar tooth and the other affecting a mandibular incisor tooth. Diagnostic imaging, including radiographs, computed tomography, and oral endoscopy was performed in order to quantify dental disease. Diagnostic imaging was also used to guide treatment of acquired dental disease, which included intraoral restoration of normal occlusal plane and tooth extraction using an extraoral approach. These are the first histologically confirmed cases of elodontoma in guinea pigs.
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http://dx.doi.org/10.1177/089875641503200205DOI Listing
November 2015

Cognitive psychotherapy treatment decreases peripheral oxidative stress parameters associated with major depression disorder.

Biol Psychol 2015 Sep 5;110:175-81. Epub 2015 Aug 5.

Programa de Pós-Graduação em Saúde e Comportamento - Universidade Católica de Pelotas, Pelotas, RS, Brazil. Electronic address:

Introduction: Studies have already pointed out the contribution of oxidative stress in the pathophysiology of major depressive disorder (MDD). The aim of the present study was to investigate the oxidative-antioxidative systems in MDD and in response to cognitive psychotherapies. Oxidative stress were analyzed in 49 MDD patients at baseline, post-treatment, and follow-up; and 49 control subjects without history of psychiatric disorders.

Results: MDD subjects presented an increase in oxidative damage related to control subjects for thiobarbituric acid reactive species (TBARS), nitric oxide, and a decrease in total thiol content. Cognitive psychotherapies were able to counteract peripheral oxidative stress in MDD patients, reducing TBARS levels (p<0.001) in the follow-up, nitric oxide (p<0.001) in the post-treatment and follow-up, and increasing the total thiol content (p<0.01) in the post-treatment and follow-up.

Conclusion: Oxidative stress was associated with MDD and the regulation of these parameters might represent an important mechanism associated with the clinical improvement of cognitive psychotherapy.
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http://dx.doi.org/10.1016/j.biopsycho.2015.08.001DOI Listing
September 2015

Primary angiocentric/angioinvasive T-cell lymphoma of the tympanic bulla in a feline leukaemia virus-positive cat.

JFMS Open Rep 2015 Jul-Dec;1(2):2055116915593966. Epub 2015 Jul 6.

Department of Veterinary Science and Public Health, Faculty of Veterinary Medicine, University of Milan, Milan, Italy.

A 5-year-old neutered female feline leukaemia virus (FeLV)-positive domestic shorthair cat with a 5 month history of otitis media was referred for head tilt, stertor and dyspnoea. Computed tomography scan revealed soft tissue opacities inside the right tympanic bulla, with bone remodelling, and concurrent nasopharyngeal and intracranial invasion. Endoscopically guided bioptic samples were collected from the nasopharynx and middle ear. Histology revealed dense sheets of round, large, neoplastic cells, often surrounding or invading vascular walls. Neoplastic cells expressed CD3, FeLV p27 and gp70 antigens. A middle ear angiocentric/angioinvasive T-cell lymphoma was diagnosed. After improvement of clinical conditions following radiation therapy, the cat died unexpectedly. At necropsy, hepatic and splenic spread was detected. Primary middle ear tumours are rare and their diagnosis is often delayed as clinical signs mimic more common otological conditions. Multiple bioptic specimens are pivotal for a definitive diagnosis. The young age of the cat, serology and immunohistochemistry revealed a possible transforming role of FeLV.
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http://dx.doi.org/10.1177/2055116915593966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362019PMC
July 2015

The Met allele of BDNF Val66Met polymorphism is associated with increased BDNF levels in generalized anxiety disorder.

Psychiatr Genet 2015 Oct;25(5):201-7

aPost Graduation in Health and Behavior, Catholic University of Pelotas, Pelotas, RS bCellular and Molecular Biology, Pontifical Catholic University of Rio Grande do Sul cEndocrinology Service dDepartment of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

Background: Generalized anxiety disorder (GAD) is a common psychiatric disorder characterized by long-term worry, tension, nervousness, fidgeting, and symptoms of autonomic system hyperactivity. The neurobiology of this disorder is still unclear, although it has been shown consistently that the environment and the genetic profile could increase its risk. We examined whether a polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which plays a role in neuroplasticity and memory, could increase the vulnerability to this disorder.

Participants And Methods: In our study, 816 participants from a population-based study were genotyped by qPCR for the BDNF functional variant rs6265 (Val66Met) and the BDNF serum levels were measured by ELISA.

Results: Our results showed a significant association between the Met allele and risk for GAD (P=0.014), but no differences were observed in the serum levels of BDNF according to diagnosis (P=0.531) or genotype distribution (P=0.197). However, after stratification according to the GAD diagnosis, the Met allele was associated significantly with an increase in serum BDNF levels compared with the Val/Val genotype in GAD participants (F=3.93; P=0.048). The logistic regression analysis confirmed the independent association of Met allele as a risk factor for development of GAD after adjusting for confounder variables (β=0.528; 95% confidence interval: 0.320-0.871; P=0.012).

Conclusion: These results suggest that BDNF could be involved in the neurobiology of GAD and might represent a useful marker associated with the disease.
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http://dx.doi.org/10.1097/YPG.0000000000000097DOI Listing
October 2015

Preventive Effect of Cecropia pachystachya Against Ketamine-Induced Manic Behavior and Oxidative Stress in Rats.

Neurochem Res 2015 Jul 22;40(7):1421-30. Epub 2015 May 22.

Programa de Pós-Graduação em Saúde e Comportamento, Centro de Ciências da Vida e da Saúde, Universidade Católica de Pelotas, Rua Gonçalves Chaves 373, Pelotas, RS, 96015560, Brazil.

Cecropia species are widely used in traditional medicine by its anti-diabetic, anti-hypertensive and anti-inflammatory properties. In the present study, we investigated the neuroprotective and antioxidant effects of the crude aqueous extract from Cecropia pachystachya leaves in a rat model of mania induced by ketamine. The results indicated that ketamine treatment (25 mg/kg i.p., for 8 days) induced hyperlocomotion in the open-field test and oxidative damage in prefrontal cortex and hippocampus, evaluated by increased lipid peroxidation, carbonyl protein formation and decreased total thiol content. Moreover, ketamine treatment reduced the activity of the antioxidant enzymes superoxide dismutase and catalase in hippocampus. Pretreatment of rats with C. pachystachya aqueous extract (200 and 400 mg/kg p.o., for 14 days) or with lithium chloride (45 mg/kg p.o., for 14 days, used as a positive control) prevented both behavioral and pro-oxidant effects of ketamine. These findings suggest that C. pachystachya might be a useful tool for preventive intervention in bipolar disorder, reducing the episode relapse and the oxidative damage associated with the manic phase of this disorder .
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http://dx.doi.org/10.1007/s11064-015-1610-5DOI Listing
July 2015