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Article Dans Une Revue Journal of Neural Transmission Année : 2023

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

Aditi Verma
Reddy Peera Kommaddi
Barathan Gnanabharathi
Etienne Hirsch
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Vijayalakshmi Ravindranath

Résumé

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.
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Dates et versions

inserm-04002894 , version 1 (12-04-2023)

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Citer

Aditi Verma, Reddy Peera Kommaddi, Barathan Gnanabharathi, Etienne Hirsch, Vijayalakshmi Ravindranath. Genes critical for development and differentiation of dopaminergic neurons are downregulated in Parkinson’s disease. Journal of Neural Transmission, 2023, 130 (4), pp.495-512. ⟨10.1007/s00702-023-02604-x⟩. ⟨inserm-04002894⟩
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