Publications by authors named "Silvia Mandillo"

17 Publications

  • Page 1 of 1

A Non-invasive Digital Biomarker for the Detection of Rest Disturbances in the SOD1G93A Mouse Model of ALS.

Front Neurosci 2020 1;14:896. Epub 2020 Sep 1.

Institute of Biochemistry and Cell Biology-National Research Council (IBBC-CNR), CNR-Campus International Development (EMMA-INFRAFRONTIER-IMPC), Monterotondo, Italy.

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that affects both central and peripheral nervous system, leading to the degeneration of motor neurons, which eventually results in muscle atrophy, paralysis, and death. Sleep disturbances are common in patients with ALS, leading to even further deteriorated quality of life. Investigating methods to potentially assess sleep and rest disturbances in animal models of ALS is thus of crucial interest. We used an automated home cage monitoring system (DVC) to capture irregular activity patterns that can potentially be associated with sleep and rest disturbances and thus to the progression of ALS in the SOD1G93A mouse model. DVC enables non-intrusive 24/7 long term animal activity monitoring, which we assessed together with body weight decline and neuromuscular function deterioration measured by grid hanging and grip strength tests in male and female mice from 7 until 24 weeks of age. We show that as the ALS progresses over time in SOD1G93A mice, activity patterns start becoming irregular, especially during day time, with frequent activity bouts that are neither observed in control mice nor in SOD1G93A at a younger age. The increasing irregularities of activity pattern are quantitatively captured by designing a novel digital biomarker, referred to as Regularity Disruption Index (RDI). We show that RDI is a robust measure capable of detecting home cage activity patterns that could be related to rest/sleep-related disturbances during the disease progression. Moreover, the RDI rise during the early symptomatic stage parallels grid hanging and body weight decline. The non-intrusive long-term continuous monitoring of animal activity enabled by DVC has been instrumental in discovering novel activity patterns potentially correlated, once validated, with sleep and rest disturbances in the SOD1G93A mouse model of the ALS disease.
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http://dx.doi.org/10.3389/fnins.2020.00896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490341PMC
September 2020

Prolonged Voluntary Running Negatively Affects Survival and Disease Prognosis of Male SOD1G93A Low-Copy Transgenic Mice.

Front Behav Neurosci 2018 13;12:275. Epub 2018 Nov 13.

Istituto di Biologia Cellulare e Neurobiologia, Consiglio Nazionale delle Ricerche, Rome, Italy.

Amyotrophic Lateral Sclerosis (ALS) is a disease in which physical activity plays a controversial role. Epidemiological studies indicate an association between intense exercise and risk of developing ALS. To study the impact of physical activity on ALS, mouse models rely mostly on forced exercise. In this study we hypothesized that voluntary wheel running could represent a better model of the influence of exercise in the pathogenesis of ALS. We used an automated home-cage running-wheel system that enables individual monitoring of performance. To verify the effect of voluntary running on disease progression, prognosis and survival as well as motor functions, we challenged SOD1G93A low-copy male and female mice on one (1 RW, at age 24 weeks) or multiple (3 RW) running sessions at age 13, 18, and 24 weeks. In parallel we measured performance on Rotarod and Grip strength tests at different ages. Several parameters were analyzed through Principal Component Analysis in order to detect what indices correlate and may be useful for deeper understanding of the relation between exercise and disease development. We found mutant male mice more negatively affected than females by prolonged and repeated exercise. SOD1G93A low-copy male mice showed shorter survival, increased body weight loss and poorer disease prognosis when exposed to multiple running sessions. These findings could encourage the investigation of the pathogenetic mechanisms underlying the supposedly increased risk to develop ALS in humans engaged in specific and intense exercise activities.
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http://dx.doi.org/10.3389/fnbeh.2018.00275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243076PMC
November 2018

MicroRNA degradation by a conserved target RNA regulates animal behavior.

Nat Struct Mol Biol 2018 03 26;25(3):244-251. Epub 2018 Feb 26.

Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.

microRNAs (miRNAs) repress target transcripts through partial complementarity. By contrast, highly complementary miRNA-binding sites within viral and artificially engineered transcripts induce miRNA degradation in vitro and in cell lines. Here, we show that a genome-encoded transcript harboring a near-perfect and deeply conserved miRNA-binding site for miR-29 controls zebrafish and mouse behavior. This transcript originated in basal vertebrates as a long noncoding RNA (lncRNA) and evolved to the protein-coding gene NREP in mammals, where the miR-29-binding site is located within the 3' UTR. We show that the near-perfect miRNA site selectively triggers miR-29b destabilization through 3' trimming and restricts its spatial expression in the cerebellum. Genetic disruption of the miR-29 site within mouse Nrep results in ectopic expression of cerebellar miR-29b and impaired coordination and motor learning. Thus, we demonstrate an endogenous target-RNA-directed miRNA degradation event and its requirement for animal behavior.
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http://dx.doi.org/10.1038/s41594-018-0032-xDOI Listing
March 2018

Analytic information processing style in epilepsy patients.

Epilepsy Behav 2017 08 9;73:18-22. Epub 2017 Jun 9.

Department of Neurophysiology, Istituto Neurologico C. Besta, Milano, Italy.

Relevant to the study of epileptogenesis is learning processing, given the pivotal role that neuroplasticity assumes in both mechanisms. Recently, evoked potential analyses showed a link between analytic cognitive style and altered neural excitability in both migraine and healthy subjects, regardless of cognitive impairment or psychological disorders. In this study we evaluated analytic/global and visual/auditory perceptual dimensions of cognitive style in patients with epilepsy. Twenty-five cryptogenic temporal lobe epilepsy (TLE) patients matched with 25 idiopathic generalized epilepsy (IGE) sufferers and 25 healthy volunteers were recruited and participated in three cognitive style tests: "Sternberg-Wagner Self-Assessment Inventory", the C. Cornoldi test series called AMOS, and the Mariani Learning style Questionnaire. Our results demonstrate a significant association between analytic cognitive style and both IGE and TLE and respectively a predominant auditory and visual analytic style (ANOVA: p values <0,0001). These findings should encourage further research to investigate information processing style and its neurophysiological correlates in epilepsy.
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http://dx.doi.org/10.1016/j.yebeh.2017.05.016DOI Listing
August 2017

Response, use and habituation to a mouse house in C57BL/6J and BALB/c mice.

Exp Anim 2015 8;64(3):281-93. Epub 2015 Apr 8.

IRCCS Santa Lucia Foundation, Via Fosso del Fiorano 64, 00143 Rome, Italy.

Animal welfare depends on the possibility to express species-specific behaviours and can be strongly compromised in socially and environmentally deprived conditions. Nesting materials and refuges are very important resources to express these behaviours and should be considered as housing supplementation items. We evaluated the effects of one item of housing supplementation in standard settings in laboratory mice. C57BL/6JOlaHsd (B6) and BALB/cOlaHsd (BALB) young male and female mice, upon arrival, were housed in groups of four in standard laboratory cages and after 10 days of acclimatization, a red transparent plastic triangular-shaped Mouse House™ was introduced into half of the home cages. Animals with or without a mouse house were observed in various contexts for more than one month. Body weight gain and food intake, home cage behaviours, emotionality and response to standard cage changing procedures were evaluated. The presence of a mouse house in the home cage did not interfere with main developmental and behavioural parameters or emotionality of BALB and B6 male and female mice compared with controls. Both strains habituated to the mouse house in about a week, but made use of it differently, with BALB mice using the house more than the B6 strain. Our results suggest that mice habituated to the mouse house rather quickly without disrupting their home cage activities. Scientists can thus be encouraged to use mouse houses, also in view of the implementation of the EU Directive (2010/63/EU).
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http://dx.doi.org/10.1538/expanim.14-0104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548001PMC
April 2016

Early motor deficits in mouse disease models are reliably uncovered using an automated home-cage wheel-running system: a cross-laboratory validation.

Dis Model Mech 2014 Mar 13;7(3):397-407. Epub 2014 Jan 13.

CNR - Institute of Cell Biology and Neurobiology - EMMA, 00015 Monterotondo Scalo, Italy.

Deficits in motor function are debilitating features in disorders affecting neurological, neuromuscular and musculoskeletal systems. Although these disorders can vary greatly with respect to age of onset, symptomatic presentation, rate of progression and severity, the study of these disease models in mice is confined to the use of a small number of tests, most commonly the rotarod test. To expand the repertoire of meaningful motor function tests in mice, we tested, optimised and validated an automated home-cage-based running-wheel system, incorporating a conventional wheel with evenly spaced rungs and a complex wheel with particular rungs absent. The system enables automated assessment of motor function without handler interference, which is desirable in longitudinal studies involving continuous monitoring of motor performance. In baseline studies at two test centres, consistently significant differences in performance on both wheels were detectable among four commonly used inbred strains. As further validation, we studied performance in mutant models of progressive neurodegenerative diseases--Huntington's disease [TgN(HD82Gln)81Dbo; referred to as HD mice] and amyotrophic lateral sclerosis [Tg(SOD1G93A)(dl)1/GurJ; referred to as SOD1 mice]--and in a mutant strain with subtle gait abnormalities, C-Snap25(Bdr)/H (Blind-drunk, Bdr). In both models of progressive disease, as with the third mutant, we could reliably and consistently detect specific motor function deficits at ages far earlier than any previously recorded symptoms in vivo: 7-8 weeks for the HD mice and 12 weeks for the SOD1 mice. We also conducted longitudinal analysis of rotarod and grip strength performance, for which deficits were still not detectable at 12 weeks and 23 weeks, respectively. Several new parameters of motor behaviour were uncovered using principal component analysis, indicating that the wheel-running assay could record features of motor function that are independent of rotarod performance. This represents a powerful new method to detect motor deficits at pre-symptomatic stages in mouse disease models and should be considered as a valid tool to investigate the efficacy of therapeutic agents.
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http://dx.doi.org/10.1242/dmm.013946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944499PMC
March 2014

Precocious cerebellum development and improved motor functions in mice lacking the astrocyte cilium-, patched 1-associated Gpr37l1 receptor.

Proc Natl Acad Sci U S A 2013 Oct 23;110(41):16486-91. Epub 2013 Sep 23.

Consiglio Nazionale delle Ricerche, European Mouse Mutant Archive-Infrafrontier-International Mouse Phenotyping Consortium, Istituto di Biologia Cellulare e Neurobiologia, I-00015 Monterotondo Scalo (Rome), Italy.

In the developing cerebellum, the proliferation and differentiation of glial and neuronal cell types depend on the modulation of the sonic hedgehog (Shh) signaling pathway. The vertebrate G-protein-coupled receptor 37-like 1 (GPR37L1) gene encodes a putative G-protein-coupled receptor that is expressed in newborn and adult cerebellar Bergmann glia astrocytes. This study shows that the ablation of the murine Gpr37l1 gene results in premature down-regulation of proliferation of granule neuron precursors and precocious maturation of Bergmann glia and Purkinje neurons. These alterations are accompanied by improved adult motor learning and coordination. Gpr37l1(-/-) mice also exhibit specific modifications of the Shh signaling cascade. Specific assays show that in Bergmann glia cells Gpr37l1 is associated with primary cilium membranes and it specifically interacts and colocalizes with the Shh primary receptor, patched 1. These findings indicate that the patched 1-associated Gpr37l1 receptor participates in the regulation of postnatal cerebellum development by modulating the Shh pathway.
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http://dx.doi.org/10.1073/pnas.1314819110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799331PMC
October 2013

A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains.

Genome Biol 2013 Jul 31;14(7):R82. Epub 2013 Jul 31.

Background: The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms.

Results: We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems.

Conclusions: Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.
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http://dx.doi.org/10.1186/gb-2013-14-7-r82DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053787PMC
July 2013

Analytic information processing style in migraineurs.

Neurol Sci 2013 Jul 19;34(7):1145-50. Epub 2012 Sep 19.

Institute of Internal Medicine VI, Headache Center, Sapienza University of Rome, Viale del Policlinico, 00161 Rome, Italy.

Despite great advances in pathophysiological facets of migraine that have been made during recent years, as of today, migraine etiology is still not completely understood; moreover, to date the relationship between psychological factors and this primary headache must be further elucidated. However, abnormal information processing, as measured by evoked and event-related potentials, has been considered a key feature in migraine pathogenesis. The aim of this work was to study the relationships between analytic/global style of information processing and migraine, hypothesizing an analytic style, as highlighted by our previous study on cluster headache. This study applied three cognitive style tests never previously used in the context of migraine: "Sternberg-Wagner Self-Assessment Inventory", the C. Cornoldi test series called AMOS, and Brain-Dominance Questionnaire. 280 migraneurs with and without aura were tested and matched with two control groups: healthy subjects and tension-type headache patients. Our results demonstrated a strong correlation between analytic information processing style and migraine, indicating a preference toward a visual sensory approach in migraine without aura, in line with known neuroelectrophysiological data. These findings may suggest a role for this specific cognitive behavior in migraine pathogenesis, leading us to further investigate the neuroelectrophysiological, neurobiological, and epigenetic correlates.
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http://dx.doi.org/10.1007/s10072-012-1193-8DOI Listing
July 2013

Absence of the GPR37/PAEL receptor impairs striatal Akt and ERK2 phosphorylation, DeltaFosB expression, and conditioned place preference to amphetamine and cocaine.

FASEB J 2011 Jun 3;25(6):2071-81. Epub 2011 Mar 3.

Istituto di Biologia Cellulare-Consiglio Nazionale delle Ricerche, Campus A. Buzzati-Traverso, Via E. Ramarini 32, I-00015 Monterotondo Scalo, Rome, Italy.

The orphan G-protein-coupled receptor 37 (GPR37) colocalizes with the dopamine (DA) transporter (DAT) in mouse nigrostriatal presynaptic membranes, and its genetic ablation in homozygous null-mutant (GPR37-KO) mice provokes the marked increase of plasma membrane expression of DAT, alteration of psychostimulant-induced locomotor activity, and reduction of catalepsy induced by DA-receptor antagonists. We report that extracts from GPR37-KO mice displayed biochemical alterations of the nigrostriatal signaling pathways mediated by D1 and D2 dopaminergic receptors. Null-mutant mice showed an increase of the basal phosphorylation level of the D2-regulated Akt kinase. The basal phosphorylation of the D1-activated ERK2 kinase was not altered, but acute treatments with amphetamine or cocaine failed to produce its specific increase, as detected in samples from wild-type littermates. Furthermore, the chronic administration of cocaine to GPR37-KO mice did not increase the expression of the ΔFosB transcription factor isoforms. Consistently, behavioral analysis showed that null-mutant animals did not respond to the incentive properties of amphetamine or cocaine, in conditioned place preference tests. Thus, the lack of GPR37 affects both ERK2- and Akt-mediated striatal signaling pathways, impairing the biochemical and behavioral responses typically induced by acute and chronic administration of psychostimulant drugs.
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http://dx.doi.org/10.1096/fj.10-175737DOI Listing
June 2011

Macroautophagy of the GPR37 orphan receptor and Parkinson disease-associated neurodegeneration.

Autophagy 2009 Jul 9;5(5):741-2. Epub 2009 Jul 9.

Istituto di Biologia Cellulare-Consiglio Nazionale delle Ricerche, Campus A. Buzzati-Traverso, Roma, Italy.

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http://dx.doi.org/10.4161/auto.5.5.8700DOI Listing
July 2009

Induction of macroautophagy by overexpression of the Parkinson's disease-associated GPR37 receptor.

FASEB J 2009 Jun 13;23(6):1978-87. Epub 2009 Feb 13.

Istituto di Biologia Cellulare-CNR, Campus A. Buzzati-Traverso, Via E. Ramarini 32, I-00015 Monterotondo Scalo, Rome, Italy.

The orphan G-protein-coupled receptor 37 (GPR37) is a substrate of parkin, and its insoluble aggregates accumulate in brain tissue samples of Parkinson's disease patients, including Lewy bodies and neurites. Parkin activates the clearance of the unfolded receptor, while the overexpression of GPR37, in the absence of parkin, can lead to unfolded protein-induced cell death. We found that overexpression of the human GPR37 receptor in HEK293 cells and consequent activation of an endoplasmic reticulum (ER) stress response had effects comparable to starvation, in inducing the cellular autophagic pathway. Treatment with specific modulators provided further evidence for the autophagic clearance of the overexpressed GPR37 protein, in detergent-soluble and -insoluble fractions, as confirmed by the conversion of the microtubule-associated protein 1, light chain 3 (LC3)-I marker to its LC3-II isoform. Furthermore, Gpr37-null mutant mice displayed consistent alterations of ER stress and autophagic pathway markers in brain tissue samples. These findings show that GPR37 overexpression per se can induce cellular autophagy, which may prevent the selective degeneration of GPR37-expressing neurons, as reported for Parkinson's and related neurodegenerative diseases.
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http://dx.doi.org/10.1096/fj.08-121210DOI Listing
June 2009

Reliability, robustness, and reproducibility in mouse behavioral phenotyping: a cross-laboratory study.

Physiol Genomics 2008 Aug 27;34(3):243-55. Epub 2008 May 27.

Gesellschaft für Strahlenforschungdagger-National Research Center for Environment and Health, Institute of Developmental Genetics, Neuherberg, Germany.

Establishing standard operating procedures (SOPs) as tools for the analysis of behavioral phenotypes is fundamental to mouse functional genomics. It is essential that the tests designed provide reliable measures of the process under investigation but most importantly that these are reproducible across both time and laboratories. For this reason, we devised and tested a set of SOPs to investigate mouse behavior. Five research centers were involved across France, Germany, Italy, and the UK in this study, as part of the EUMORPHIA program. All the procedures underwent a cross-validation experimental study to investigate the robustness of the designed protocols. Four inbred reference strains (C57BL/6J, C3HeB/FeJ, BALB/cByJ, 129S2/SvPas), reflecting their use as common background strains in mutagenesis programs, were analyzed to validate these tests. We demonstrate that the operating procedures employed, which includes open field, SHIRPA, grip-strength, rotarod, Y-maze, prepulse inhibition of acoustic startle response, and tail flick tests, generated reproducible results between laboratories for a number of the test output parameters. However, we also identified several uncontrolled variables that constitute confounding factors in behavioral phenotyping. The EUMORPHIA SOPs described here are an important start-point for the ongoing development of increasingly robust phenotyping platforms and their application in large-scale, multicentre mouse phenotyping programs.
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http://dx.doi.org/10.1152/physiolgenomics.90207.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519962PMC
August 2008

GPR37 associates with the dopamine transporter to modulate dopamine uptake and behavioral responses to dopaminergic drugs.

Proc Natl Acad Sci U S A 2007 Jun 22;104(23):9846-51. Epub 2007 May 22.

Istituto di Biologia Cellulare-Consiglio Nazionale delle Ricerche, Campus A. Buzzati-Traverso, Via E. Ramarini 32, Monterotondo Scalo, I-00015 Rome, Italy.

The orphan G protein-coupled receptor 37 (GPR37) is a substrate of parkin; its insoluble aggregates accumulate in brain samples of Parkinson's disease patients. We report here that GPR37 interacts with the dopamine transporter (DAT) and modulates DAT activity. GPR37 and DAT were found colocalized in mouse striatal presynaptic membranes and in transfected cells and their interaction was confirmed by coimmunoprecipitation assays. Gpr37-null mutant mice showed enhanced DAT-mediated dopamine uptake in striatal membrane samples, with a significant increase in the number of plasma membrane DAT molecules. The null mutant mice also exhibited a decrease in cocaine-induced locomotor activity and in catalepsy induced by dopamine receptor antagonists. These results reveal the specific role of GPR37, a putative peptidergic G protein-coupled receptor, in modulating the functional expression of DAT and the behavioral responses to dopaminergic drugs.
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http://dx.doi.org/10.1073/pnas.0703368104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1887553PMC
June 2007

D1 and D2 receptor antagonist injections in the prefrontal cortex selectively impair spatial learning in mice.

Neuropsychopharmacology 2007 Feb 9;32(2):309-19. Epub 2006 Aug 9.

Dipartimento di Genetica e Biologia Molecolare, Università di Roma La Sapienza, Rome, Italy.

The prefrontal cortex (PFC) is a cortical area involved in selecting and retaining information to produce complex behaviors. Within the PFC, the dopaminergic system plays an important role in information processing. Thus, the objective of this study was to test whether bilateral administration of the D1 and D2 receptor antagonists in the prelimbic region of the PFC influenced the performance of mice in a non-associative spatial learning task. CD1 mice were bilaterally microinjected in the PFC with either the D1 receptor antagonist, SCH23390 (SCH 6.25; 12.5; 50 ng), or the D2 receptor antagonist, sulpiride (SULP 12.5; 50; 100 ng) and placed into an open field containing five different objects. After three sessions of habituation two objects were repositioned (spatial change) and in the subsequent session one of the objects was substituted (non-spatial change). No significant alteration was observed in the habituation pattern of the animals after D1 or D2 receptor blockade. When two of the objects were displaced, control mice explored the displaced objects far more than the non-displaced ones, while mice treated with SCH or SULP spent a comparable amount of time re-exploring the two object categories. Conversely, DA antagonists had no effects on the discrimination of the new object. Thus, the administration of both SCH and SULP selectively impaired the ability of mice to discriminate a spatial change, without affecting any other behavioral parameter. These findings could provide a model to study the role of the PFC dopaminergic system in spatial learning and to study the neural mechanisms underlying cognitive and attention deficits often observed in psychiatric disorders.
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http://dx.doi.org/10.1038/sj.npp.1301176DOI Listing
February 2007

Altered dopamine signaling and MPTP resistance in mice lacking the Parkinson's disease-associated GPR37/parkin-associated endothelin-like receptor.

Proc Natl Acad Sci U S A 2004 Jul 24;101(27):10189-94. Epub 2004 Jun 24.

Istituto di Biologia Cellulare-Consiglio Nazionale delle Ricerche, Campus A. Buzzati-Traverso, Via E. Ramarini 32, I-00016 Monterotondo Scalo, Rome, Italy.

GPR37 is an orphan G protein-coupled receptor expressed in mammalian brain, and its insoluble aggregates are found in the brain samples of juvenile Parkinson's disease patients. We have produced a Gpr37 knock-out mouse strain and identified several phenotypic features that are similar to those reported for mutants of genes encoding components of synaptic dopamine vesicles. Our results reveal an unanticipated role of GPR37 in regulating substantia nigra-striatum dopaminergic signaling. Gpr37(-/-) mice are viable, with normal brain development and anatomy, but they exhibit reduced striatal dopamine content, enhanced amphetamine sensitivity, and specific deficits in motor behavior paradigms sensitive to nigrostriatal dysfunction. These functional alterations are not associated with any substantial loss of substantia nigra neurons or degeneration of striatal dopaminergic afferences, the main histological marks of Parkinson's disease. The inactivation of GPR37, in fact, has protective effects on substantia nigra neurons, causing resistance to treatment with the Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
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http://dx.doi.org/10.1073/pnas.0403661101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC454186PMC
July 2004

Effects of acute and repeated daily exposure to hypergravity on spatial learning in mice.

Neurosci Lett 2003 Jan;336(3):147-50

Dip di Genetica e Biologia Molecolare, Università "La Sapienza", P le A Moro 5, 00185, Roma, Italy.

Studies in humans have revealed that exposure to altered gravity may lead to impairments in cognitive functions. The objective of this study was to test whether mice exposed to hypergravity using a centrifuge apparatus showed learning impairments in a spatial learning task. Mice rotating at 1G or at 2G acceleration gravity and non-rotating controls were tested for reactivity to a spatial change after either a single 1 h or five repeated 1 h daily rotations in the centrifuge. While no differences among groups were found in the performance after single exposure to altered gravity, 5 days of repeated exposures to 1G or 2G gravity conditions significantly affected mouse ability to discriminate a new spatial arrangement. Additionally, this effect was stronger in the animals repeatedly exposed to 2G rather than to 1G conditions.
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http://dx.doi.org/10.1016/s0304-3940(02)01282-xDOI Listing
January 2003