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Cumulative low doses of the organic pesticide rotenone in the adult rat substantia nigra pars compacta

ABSTRACT: Adult male Sprague Dawley rats (5 month-old at the beginning of the study) were subcutaneously exposed to 0.5 mg.kg/d rotenone or the corresponding solvent (PEG/DMSO, 1/1) for 28 days. At the end of the experiment, animals were sacrificed by decapitation and brains were rapidly taken out within 30-40 s. Total RNA was prepared from laser-capture microdissected rat substantia nigra pars compacta (Snpc). Changes in transcript abundance within SNpc were analyzed on samples from solvent and rotenone-exposed groups (n = 3 per group) using CodeLink™ Rat Whole Genome bioarrays containing 34,000 transcripts and EST probes (GE Healthcare, Amersham, Saclay, France).

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE22364 | GEO | 2015/12/31

SECONDARY ACCESSION(S): PRJNA127675

REPOSITORIES: GEO

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Cumulative low doses of the organic pesticide rotenone in the adult rat substantia nigra pars compacta

Project description:Adult male Sprague Dawley rats (5 month-old at the beginning of the study) were subcutaneously exposed to 0.5 mg.kg/d rotenone or the corresponding solvent (PEG/DMSO, 1/1) for 28 days. At the end of the experiment, animals were sacrificed by decapitation and brains were rapidly taken out within 30-40 s. Total RNA was prepared from laser-capture microdissected rat substantia nigra pars compacta (Snpc). Changes in transcript abundance within SNpc were analyzed on samples from solvent and rotenone-exposed groups (n = 3 per group) using CodeLinkâ¢ Rat Whole Genome bioarrays containing 34,000 transcripts and EST probes (GE Healthcare, Amersham, Saclay, France). Two groups of rats were exposed either to rotenone (CR rats) or to solvents (CS rats) in order to analyse pesticides impact on gene expression.

2015-12-31 | E-GEOD-22364 | biostudies-arrayexpress

RNA-SEQ profiling of dopaminergic neurons from the substantia nigra pars compacta and ventral tegmental area regions of the mouse mid-brain

Project description:RNA-SEQ profiling of dopaminergic neurons from the substantia nigra pars compacta and ventral tegmental area regions of the mouse mid-brain Murine midbrain dopaminergic neurons from the SNpc and VTA regions

2015-07-27 | E-GEOD-64452 | biostudies-arrayexpress

Age-mediated transcriptomic changes in adult mouse substantia nigra

2013-05-29 | GSE45043 | GEO

Age-mediated transcriptomic changes in adult mouse substantia nigra

Project description:Substantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. Until now, molecular mechanisms behind SNpc aging have not been fully investigated using high throughput techniques. Here, aging-associated early changes in transcriptome of SNpc were investigated comparing late middle-aged (18 months old) to young (2 months old) mice. Three age groups of C57 wild type mice were used in microarray analysis: young (2 months old), middle aged (10 months old), and late-middle aged (18 months old) mice. Four replicates were included in each age group and each replicate was pooled from 4 mice (4 mice/replicate x 4 replicates x 3 age groups). Total RNA was isolated from SNpc for hybridization on Affymetrix microarrays.

2013-05-29 | E-GEOD-45043 | biostudies-arrayexpress

Single-cell analysis of gene expression in the substantia nigra pars compacta of a pesticide-induced mouse model of Parkinson's disease.

Project description:Exposure to pesticides in humans increases the risk of Parkinson's disease (PD), but the mechanisms remain poorly understood. To elucidate these pathways, we dosed C57BL/6J mice with a combination of the pesticides maneb and paraquat. Behavioral analysis revealed motor deficits consistent with PD. Single-cell RNA sequencing of substantia nigra pars compacta revealed both cell-type-specific genes and genes expressed differentially between pesticide and control, including Fam241b, Emx2os, Bivm, Gm1439, Prdm15, and Rai2. Neurons had the largest number of significant differentially expressed genes, but comparable numbers were found in astrocytes and less so in oligodendrocytes. In addition, network analysis revealed enrichment in functions related to the extracellular matrix. These findings emphasize the importance of support cells in pesticide-induced PD and refocus our attention away from neurons as the sole agent of this disorder.

| S-EPMC9438968 | biostudies-literature

Mesencephalic origin of the rostral Substantia nigra pars reticulata.

Project description:In embryonic development, the neurons that will constitute a heterogeneous nucleus may have distinct origins. The different components of these populations reach their final location by radial and tangential migrations. The Substantia nigra pars reticulata (SNR) presents a high level of neuronal heterogeneity. It is composed by GABAergic neurons located in the mes-diencephalic basal plate. These inhibitory neurons usually display tangential migrations and it has been already described that the caudal SNR is colonized tangentially from rhombomere 1. Our aim is to unveil the origin of the rostral SNR. We have localized a Nkx6.2 positive ventricular domain located in the alar midbrain. Nkx6.2 derivatives' fate map analysis showed mainly a rostral colonization of this GABAergic neuronal population. We confirmed the mesencephalic origin by the expression of Six3. Both transcription factors are sequentially expressed along the differentiation of these neurons. We demonstrated the origin of the rostral SNR; our data allowed us to postulate that this nucleus is composed by two neuronal populations distributed in opposite gradients with different origins, one from rhombomere 1, caudal to rostral, and the other from the midbrain, rostral to caudal. We can conclude that the SNR has multiple origins and follows complex mechanisms of specification and migration. Our results support vital information for the study of genetic modifications in these extremely complex processes that result in devastating behavioral alterations and predisposition to psychiatric diseases. Understanding the development, molecular identity and functional characteristics of these diverse neuronal populations might lead to better diagnosis and treatment of several forms of neurological and psychiatric disease.

| S-EPMC4819793 | biostudies-literature

Deep sequencing of endogenous mRNA from Caenorhabditis elegans in the presence and absence of rotenone at 4 different time points

Project description:Background: We here show that inhibitors of mitochondrial complex I promote physical activity, stress resistance as well as lifespan of Caenorhabditis elegans despite normal food uptake, i.e. in the absence of DR. Dietary restriction (DR) extends lifespan and promotes metabolic health in evolutionary distinct species. The RNA-seq data comprises 4 age groups (1, 5, 10 and 20 days after L4) and 2 different conditions (rotenone and normal feeding (DMSO)) 22 samples: mRNA profiles of 1-day, 5-day and 10-day old worms as triplicates for each, rotenone and solvent control treatment; mRNA profiles of 20-day old worms as duplicates for each, rotenone and solvent control treatment

2013-04-16 | E-GEOD-46051 | biostudies-arrayexpress

Transcriptomes of individual substantia nigra pars reticulata neurons

Project description:Certain neuron types fire spontaneously at high rates, an ability that is crucial for their function in brain circuits. The spontaneously active GABAergic neurons of the substantia nigra pars reticulata (SNr), a major output of the basal ganglia, provide tonic inhibition of downstream brain areas. A depolarizing "leak" current supports this firing pattern, but its molecular basis remains poorly understood. To understand how SNr neurons maintain tonic activity, we used single-cell RNA sequencing to determine the transcriptome of individual SNr neurons. We discovered that SNr neurons express the sodium leak current, NaLCN and that SNr neurons lacking NaLCN have impaired spontaneous firing.

2016-05-13 | GSE78521 | GEO

Substantia Nigra Pars Reticulata Projections to the Pedunculopontine Nucleus Modulate Dyskinesia.

Project description:BackgroundLong-term use of levodopa for Parkinson's disease (PD) treatment is often hindered by development of motor complications, including levodopa-induced dyskinesia (LID). The substantia nigra pars reticulata (SNr) and globus pallidus internal segment (GPi) are the output nuclei of the basal ganglia. Dysregulation of SNr and GPi activity contributes to PD pathophysiology and LID.ObjectiveThe objective of this study was to determine whether direct modulation of SNr GABAergic neurons and SNr projections to the pedunculopontine nucleus (PPN) regulates PD symptoms and LID in a mouse model.MethodsWe expressed Cre-recombinase activated channelrhodopsin-2 (ChR2) or halorhodopsin adeno-associated virus-2 (AAV2) vectors selectively in SNr GABAergic neurons of Vgat-IRES-Cre mice in a 6-hydroxydopamine model of PD to investigate whether direct optogenetic modulation of SNr neurons or their projections to the PPN regulates PD symptoms and LID expression. The forepaw stepping task, mouse LID rating scale, and open-field locomotion were used to assess akinesia and LID to test the effect of SNr modulation.ResultsAkinesia was improved by suppressing SNr neuron activity with halorhodopsin. LID was significantly reduced by increasing SNr neuronal activity with ChR2, which did not interfere with the antiakinetic effect of levodopa. Optical stimulation of ChR2 in SNr projections to the PPN recapitulated direct SNr stimulation.ConclusionsModulation of SNr GABAergic neurons alters akinesia and LID expression in a manner consistent with the rate model of basal ganglia circuitry. Moreover, the projections from SNr to PPN likely mediate the antidyskinetic effect of increasing SNr neuronal activity, identifying a potential novel role for the PPN in LID. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

| S-EPMC10932617 | biostudies-literature

Intraoperative Microelectrode Recordings in Substantia Nigra Pars Reticulata in Anesthetized Rats.

Project description:The Substantia Nigra pars reticulata (SNr) is a promising target for deep brain stimulation (DBS) to treat the gait and postural disturbances in Parkinson's disease (PD). Positioning the DBS electrode within the SNr is critical for the development of preclinical models of SNr DBS to investigate underlying mechanisms. However, a complete characterization of intraoperative microelectrode recordings in the SNr to guide DBS electrode placement is lacking. In this study, we recorded extracellular single-unit activity in anesthetized rats at multiple locations in the medial SNr (mSNr), lateral SNr (lSNr), and the Ventral Tegmental Area (VTA). Immunohistochemistry and fluorescently dyed electrodes were used to map neural recordings to neuroanatomy. Neural recordings were analyzed in the time domain (i.e., firing rate, interspike interval (ISI) correlation, ISI variance, regularity, spike amplitude, signal-to-noise ratio, half-width, asymmetry, and latency) and the frequency domain (i.e., spectral power in frequency bands of interest). Spike amplitude decreased and ISI correlation increased in the mSNr versus the lSNr. Spike amplitude, signal-to-noise ratio, and ISI correlation increased in the VTA versus the mSNr. ISI correlation increased in the VTA versus the lSNr. Spectral power in the VTA increased versus: (1) the mSNr in the 20-30 Hz band and (2) the lSNr in the 20-40 Hz band. No significant differences were observed between structures for any other feature analyzed. Our results shed light on the heterogeneity of the SNr and suggest electrophysiological features to promote precise targeting of SNr subregions during stereotaxic surgery.

| S-EPMC7201294 | biostudies-literature

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