Dataset Information

Spatiotemporal Proteomic and Transcriptomic Landscape of DAT+ Dopaminergic Neurons Development and Function

ABSTRACT: Dopaminergic (DA) neurons marked by the dopamine transporter (DAT) have multiple physiological functions and are involved in the regulation of mental and neurological diseases, prompting in-depth studies into their development and functions. This research explores the spatiotemporal proteomic and transcriptomic changes in DAT+ DA neurons within key brain regions involved in DA signaling—the nucleus accumbens (NAc), substantia nigra (SNc), and ventral tegmental area (VTA). Utilizing cutting-edge multi-omics techniques, such as ultrasensitive trace sample proteomics and SMART-seq2 for transcriptomics, we examine the DA neuronal system at critical postnatal milestones: postnatal day 7 (P7), postnatal day 30 (P30), and postnatal day 60 (P60). The study reveals unique molecular profiles within DA neuron populations, showcasing their varied functional roles and developmental progression.

ORGANISM(S): Mus Musculus

SUBMITTER: Huali Shen

PROVIDER: PXD055527 | iProX | Wed Oct 09 00:00:00 BST 2024

REPOSITORIES: iProX

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Publications

Spatiotemporal proteomic and transcriptomic landscape of DAT+ dopaminergic neurons development and function.

Zhao Heyu H Chen Peipei P Gao Xia X Huang Zhili Z Yang Pengyuan P Shen Huali H

iScience 20250227 4

Dopaminergic (DA) neurons expressing the dopamine transporter (DAT) play vital roles in physiology and the regulation of mental and neurological disorders. This study investigates spatiotemporal proteomic and transcriptomic changes in DAT+ DA neurons from key brain regions-the nucleus accumbens (NAc), substantia nigra (SNc), and ventral tegmental area (VTA)-at postnatal milestones: day 7 (P7), day 30 (P30), and day 60 (P60). Using advanced multi-omics techniques, including ultrasensitive trace s ...[more]

PMID: 40201125

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Project description:Implications for neuroprotection in Parkinson's disease Parkinson’s disease and its characteristic symptoms are thought to arise from the progressive degeneration of specific midbrain dopamine (DA) neurons. In humans, DA neurons of the substantia nigra (SN) and their projections to the striatum show selective vulnerability, while neighboring DA neurons of the ventral tegmental area (VTA) are relatively spared from degeneration. This pattern of cell loss is mimicked in humans, primates, and certain rodents by the neurotoxin MPTP. In this study, we aimed to test the hypothesis that there are factors in the VTA that are potentially neuroprotective against MPTP and that these factors change over time. We have found a differential transcriptional response within the cells of the SN and VTA to sustained exposure to a low dose of MPTP. Specifically, the VTA has increased expression of 148 genes as an early response to MPTP and 113 genes as a late response to MPTP toxicity. This response encompasses many areas of cellular function, including protein regulation (Phf6) and ion/metal regulation (PANK2, Car4). Notably, these responses were largely absent from the cells of the SN. Our data show a clear dynamic response in maintaining the homeostasis and viability of the neurons in the VTA that is lacking in the SN after neurotoxin challenge. We used microarrays to analyze the differential response of the substantia nigra (SN) and ventral tegmental area (VTA) to a chronic low dose of the neurotoxin MPTP. Transgenic hTH-GFP mice were treated with MPTP (4mg/kg) for either 2 or 10 days. Control mice were given an equal volume of saline for 10 days. Dopamine neurons from the substantia nigra and ventral tegmental areas of control and MPTP treated animals were laser captured. The RNA was isolated and processed for microarray hybridization. Each group had three biological replicates, for a total of 18 samples. Three each in the following: Control SN, Control VTA, 2 day MPTP SN, 2 day MPTP VTA, 10 day MPTP SN, 10 day MPTP VTA. Samples were log2 transformed and RMA normalized using Agilent Genespring 10.0 GX.

Dataset Information

Spatiotemporal Proteomic and Transcriptomic Landscape of DAT+ Dopaminergic Neurons Development and Function

Publications

Spatiotemporal proteomic and transcriptomic landscape of DAT+ dopaminergic neurons development and function.

Similar Datasets

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