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

Verma, A and Kommaddi, RP and Gnanabharathi, B and Hirsch, EC and Ravindranath, V (2023) Genes critical for development and differentiation of dopaminergic neurons are downregulated in Parkinson’s disease. In: Journal of Neural Transmission .

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Official URL: https://10.1007/s00702-023-02604-x


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. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.

Item Type: Journal Article
Publication: Journal of Neural Transmission
Publisher: Springer
Additional Information: The copy rights of the article belong to Springer.
Keywords: LMX1B; Neurodegeneration; RNA-seq; SH-SY5Y; Substantia nigra
Department/Centre: Division of Biological Sciences > Centre for Neuroscience
Autonomous Societies / Centres > Centre for Brain Research
Date Deposited: 13 Mar 2023 13:20
Last Modified: 13 Mar 2023 13:20
URI: https://eprints.iisc.ac.in/id/eprint/80895

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