Genes critical for development and differentiation of dopaminergic neurons are downregulated in Parkinson's disease

被引：13

作者：

Verma, Aditi ^{[1
]}

Kommaddi, Reddy Peera ^{[2
]}

Gnanabharathi, Barathan ^{[2
]}

Hirsch, Etienne C. ^{[3
]}

Ravindranath, Vijayalakshmi ^{[1
,2
]}

机构：

[1] Indian Inst Sci, Ctr Neurosci, CV Raman Ave, Bangalore 560012, India

[2] Indian Inst Sci, Ctr Brain Res, Bangalore 560012, India

[3] Sorbonne Univ, Inst Cerveau ICM, Inserm 1127, CNR UMR 7225, F-75013 Paris, France

来源：

JOURNAL OF NEURAL TRANSMISSION | 2023年 / 130卷 / 04期

关键词：

Substantia nigra; RNA-seq; LMX1B; SH-SY5Y; Neurodegeneration; SUBSTANTIA-NIGRA; TYROSINE-HYDROXYLASE; EXPRESSION; INSIGHTS; IDENTIFICATION; MODEL; BRAIN; LMX1B; NURR1; MPTP;

D O I：

10.1007/s00702-023-02604-x

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

We performed transcriptome analysis using RNA sequencing on substantia nigra pars compacta (SNpc) from mice after acute and chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment and from Parkinson's disease (PD) patients. Acute and chronic exposure to MPTP resulted in decreased expression of genes involved in sodium channel regulation. However, upregulation of pro-inflammatory pathways was seen after single dose but not after chronic MPTP treatment. Dopamine biosynthesis and synaptic vesicle recycling pathways were downregulated in PD patients and after chronic MPTP treatment in mice. Genes essential for midbrain development and determination of dopaminergic phenotype such as, LMX1B, FOXA1, RSPO2, KLHL1, EBF3, PITX3, RGS4, ALDH1A1, RET, FOXA2, EN1, DLK1, GFRA1, LMX1A, NR4A2, GAP43, SNCA, PBX1, and GRB10 were downregulated in human PD and overexpression of GFP tagged LMX1B rescued MPP+ induced death in SH-SY5Y neurons. Downregulation of gene ensemble involved in development and differentiation of dopaminergic neurons indicate their potential involvement in pathogenesis and progression of human PD.

引用

页码：495 / 512

页数：18

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