Parkinson’s Disease–Associated Changes in the Expression of Neurotrophic Factors and their Receptors upon Neuronal Differentiation of Human Induced Pluripotent Stem Cells

• Published in: Journal of molecular neuroscience Vol. 70; no. 4; pp. 514 - 521
• Main Authors: Novosadova, E. V., Nenasheva, V. V., Makarova, I. V., Dolotov, O. V., Inozemtseva, L. S., Arsenyeva, E. L., Chernyshenko, S. V., Sultanov, R. I., Illarioshkin, S. N., Grivennikov, I. A., Tarantul, V. Z.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2020; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Cell Biology; Cell Line; Cell lines; Cells, Cultured; Degeneration; Differentiation; Dopamine receptors; Dopaminergic Neurons - cytology; Dopaminergic Neurons - metabolism; Fibroblasts; Genes; Glial cell line-derived neurotrophic factor; Glial Cell Line-Derived Neurotrophic Factor - genetics; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Humans; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Inhibitory postsynaptic potentials; Levels; Movement disorders; Mutation; Neurochemistry; Neurodegeneration; Neurodegenerative diseases; Neurogenesis; Neurology; Neurons; Neurosciences; Neurotrophic factors; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson's disease; Pathogenesis; Pluripotency; Post-transcription; Proteomics; Receptor, trkB - genetics; Receptor, trkB - metabolism; Receptors; Regulators; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stem cells; Substantia nigra; Neuronal differentiation; Receptors; Neurotrophic factors; Induced pluripotent stem cells; Parkinson’s disease
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-019-01450-5

Parkinson’s disease (PD) is a neurodegenerative pathology resulting from the degeneration of dopaminergic (DA) neurons in the substantia nigra (SN). Neurotrophic factors (NTFs) and their receptors are key regulators of the survival, differentiation, and development of neurons. However, the role of these factors in the pathogenesis of PD is still unclear. Here, we analyzed the expression of NTFs and their receptors in human induced pluripotent stem cells (iPSCs) derived from the fibroblasts of patients with PD and healthy donors (HDs). Four PD-derived iPSC lines with different mutations and three cell lines from HDs at different stages of neuronal differentiation were used for RT-qPCR analysis and ELISA. We found that the mRNA levels of most analyzed genes were altered in PD-derived cells compared with those in HD-derived cells at all stages. Importantly, irrespective of PD-associated mutations, the mRNA levels of the
BDNF
and
GDNF
genes were mostly increased or unchanged in predominantly DA terminally differentiated neurons (TDNs) compared with those in HD-derived cells. Strikingly, in contrast to BDNF and GDNF mRNA levels, BDNF and GDNF protein levels were lower in almost all PD-derived TDNs than in HD-derived cells, thus indicating the dysregulation of NTF expression at the post-transcriptional level. We suggest that this dysregulation is one of the important signs of PD development.