Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA305311 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Pitx3 is a transcription factor that is expressed in all midbrain dopaminergic (mDA) neurons during early development, but later becomes restricted in dopaminergic subsets of substantia nigra compacta (SNc) and of the ventral tegmental are (VTA) that are vulnerable to neurodegenerative stress (MPTP, 6-OHDA, rotenone, Parkinson's disease). Overall, in mice, Pitx3 is required for developmental survival of ventral SNc neurons and for postnatal survival of VTA neurons (after postnatal day 40). With the aim of determining the gene networks that distinguish Pitx3-vulnerable (Pitx3-positive) from Pitx3-resistant (Pitx3-negative) subsets of SNc and VTA, we performed a comparison at the transcriptome level between FAC-sorted mDA neurons of SNc and VTA that were obtained from wild-type and Pitx3-/- newborn mice. The latter mice have already lost the majority of their TH+Calb1- mDA neurons of ventral SNc (Pitx3-dependent), but their TH+Calb1+ neurons of dorsal SNc (Pitx3-independent), including all of VTA neurons (50% are Pitx3-dependent and 50% Pitx3-independent), are unaffected by Pitx3 deletion. At postnatal day 40, Pitx3-/- mice display a marked loss of dopaminergic subsets of VTA that normally co-express Pitx3 and Calb1 (Pitx3-dependent neurons of VTA).
2016-01-31 | GSE75777 | GEO
Project description:Dopaminergic neurons located in the ventral midbrain can be broadly subdivided into two distinct subpopulations. Substantia nigra (SN) dopaminergic neurons are highly sensitive to toxic insults and selectively degenerate in Parkinson’s disease, while ventral tegmental area (VTA) dopaminergic neurons are associated with other neurological disorders. Access to enriched cultures of SN and VTA dopaminergic neuronal subpopulations will facilitate disease modelling and give insight in the differential vulnerability, but it is unclear how the differentiation of human ES cells can be directed towards these distinct lineages. We found that overexpression of the lineage specifying transcription factors Sox6 and Otx2 can direct the differentiation of human ES cells into enriched populations of respectively SN or VTA neurons. Proteomic analysis of these cultures resulted in the identification of several differential expressed proteins and provided insight in pathways contributing to the selective vulnerability of SN.
2021-11-03 | PXD028639 | Pride
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
Project description:The cardinal clinical features of Parkinson's disease result from selective loss of midbrain dopaminergic neurons. The goal of this experiment is to determine the gene expression profiles of these neurons by studying untreated rat substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) dopaminergic neurons using laser capture microscopy to obtain region-specific neuronal mRNA.
2007-10-27 | E-GEOD-1157 | biostudies-arrayexpress
Project description:Development of meso-diencephalic dopamine (mdDA) neurons requires the combined actions of the orphan nuclear receptor Nurr1 and the paired-like homeobox transcription factor Pitx3. Whereas all mdDA neurons require Nurr1 for expression of Th and survival, dependence on Pitx3 is only displayed by the mdDA subpopulation that will form the substantia nigra (SNc). Previously, we demonstrated that Pitx3-/- embryos lack the expression of the retinoic acid (RA)-generating enzyme Ahd2, which is normally selectively expressed in the Pitx3-dependent DA neurons of the SNc. Restoring RA-signaling in Pitx3-/- embryos revealed a selective dependence of SNc neurons on the presence of RA for differentiation into Th-positive neurons and maintenance throughout embryonic development. Whereas these data are suggestive of an important developmental role for RA in neurons of the SNc, it remained unclear whether other Nurr1 and Pitx3 target genes depend on RA signaling in a manner similar to Th. In search for genes that were affected in Pitx3-deficient mdDA neurons and restored upon embryonic RA treatment, we provide evidence that Delta-like 1, D2R (Drd2) and TH are regulated by Pitx3 and RA signaling, influencing the mdDA terminal differentiated phenotype. Furthermore, we show that regulation of Ahd2-mediated RA-signaling represents only one aspect of the Pitx3 downstream cascade, since Vmat2, Dat, Ahd2 (Aldh1a1), En1, En2 and Cck were unaffected by RA treatment and are (subset) specifically modulated by Pitx3. In conclusion, our data reveal several RA-dependent and -independent aspects of the Pitx3-regulated gene cascade suggesting that Pitx3 acts on multiple levels in the molecular subset-specification of mdDA neurons. RNA was isolated from dissected ventral midbrains of E14.5 Pitx3-/- and Pitx3+/+ mouse embryos. 3 Experimental samples each consisting of 3 Pitx3-/- ventral midbrains were hybridized to reference RNA derived from 10 Pitx3+/+ ventral midbrains
2011-11-22 | E-GEOD-32940 | biostudies-arrayexpress
Project description:FJ001: Retinoic acid-dependent and -independent gene-regulatory pathways of Pitx3 in meso-diencephalic dopaminergic neurons
| PRJNA146577 | ENA
Project description:Acute stress can inhibit the activity of dopaminergic neurons in the ventral tegmental area (VTA), leading to increased anxiety and reduced sensitivity to natural rewards. However, the molecular mechanisms underlying this effect remain unclear. Our study shows that acute restraint stress increases the phosphorylation of the transcription factor STAT3 at Ser727 and Tyr705 in VTA dopaminergic neurons, enhancing its transcriptional activity. This modulation contributes to the inhibition of dopaminergic neuron activity, heightened anxiety, and reduced reward sensitivity. Furthermore, acute stress also promotes O-GlcNAcylation in VTA neurons, which competes with STAT3 Ser727 but not Tyr705 phosphorylation and modulates its transcriptional activity, leading to alterations in GABA receptor expression. This reveals a complex molecular feedback mechanism where O-GlcNAcylation regulates STAT3 activity to maintain brain homeostasis during acute stress responses.
2025-09-01 | GSE276171 | GEO
Project description:Acute stress can inhibit the activity of dopaminergic neurons in the ventral tegmental area (VTA), leading to increased anxiety and reduced sensitivity to natural rewards. However, the molecular mechanisms underlying this effect remain unclear. Our study shows that acute restraint stress increases the phosphorylation of the transcription factor STAT3 at Ser727 and Tyr705 in VTA dopaminergic neurons, enhancing its transcriptional activity. This modulation contributes to the inhibition of dopaminergic neuron activity, heightened anxiety, and reduced reward sensitivity. Furthermore, acute stress also promotes O-GlcNAcylation in VTA neurons, which competes with STAT3 Ser727 but not Tyr705 phosphorylation and modulates its transcriptional activity, leading to alterations in GABA receptor expression. This reveals a complex molecular feedback mechanism where O-GlcNAcylation regulates STAT3 activity to maintain brain homeostasis during acute stress responses.
2025-09-01 | GSE276183 | GEO
Project description:Acute stress can inhibit the activity of dopaminergic neurons in the ventral tegmental area (VTA), leading to increased anxiety and reduced sensitivity to natural rewards. However, the molecular mechanisms underlying this effect remain unclear. Our study shows that acute restraint stress increases the phosphorylation of the transcription factor STAT3 at Ser727 and Tyr705 in VTA dopaminergic neurons, enhancing its transcriptional activity. This modulation contributes to the inhibition of dopaminergic neuron activity, heightened anxiety, and reduced reward sensitivity. Furthermore, acute stress also promotes O-GlcNAcylation in VTA neurons, which competes with STAT3 Ser727 but not Tyr705 phosphorylation and modulates its transcriptional activity, leading to alterations in GABA receptor expression. This reveals a complex molecular feedback mechanism where O-GlcNAcylation regulates STAT3 activity to maintain brain homeostasis during acute stress responses.
2025-09-01 | GSE276173 | GEO
Project description:Acute stress can inhibit the activity of dopaminergic neurons in the ventral tegmental area (VTA), leading to increased anxiety and reduced sensitivity to natural rewards. However, the molecular mechanisms underlying this effect remain unclear. Our study shows that acute restraint stress increases the phosphorylation of the transcription factor STAT3 at Ser727 and Tyr705 in VTA dopaminergic neurons, enhancing its transcriptional activity. This modulation contributes to the inhibition of dopaminergic neuron activity, heightened anxiety, and reduced reward sensitivity. Furthermore, acute stress also promotes O-GlcNAcylation in VTA neurons, which competes with STAT3 Ser727 but not Tyr705 phosphorylation and modulates its transcriptional activity, leading to alterations in GABA receptor expression. This reveals a complex molecular feedback mechanism where O-GlcNAcylation regulates STAT3 activity to maintain brain homeostasis during acute stress responses.
2024-09-07 | PXD055720 |