RRC ID 54827
Author Iwasawa C, Kuzumaki N, Suda Y, Kagawa R, Oka Y, Hattori N, Okano H, Narita M.
Title Reduced expression of somatostatin in GABAergic interneurons derived from induced pluripotent stem cells of patients with parkin mutations.
Journal Mol Brain
Abstract Parkinson's disease (PD) is associated with both motor and non-motor symptoms, including constipation, sensory neuropathy, depression, dementia and sleep disorder. Somatostatin (SST) is considered to be a modulator of GABAergic inhibitory transmission, and its levels are reduced in cerebrospinal fluid of PD patients. In the present study, we evaluated the changes in the expression of SST in GABAergic neurons derived from induced pluripotent stem cells (iPSCs) of PD patients. Neural cells were co-treated with the Wnt antagonist IWP-2 and Shh during neurosphere formation to induce GABA-positive forebrain interneurons. Quantitative analyses showed no significant differences, but slight decreases, in the potency of differentiation into GABAergic neurons derived from iPSCs between healthy control and patients with PARK2 mutations, who have been classified as a type of early-onset familial PD due to mutations in the parkin gene. Under this condition, the mRNA level of SST in GABAergic interneurons derived from iPSCs of PARK2-specific PD patients significantly decreased as neural maturation progressed. We also found that SST-positive GABAergic neurons were clearly reduced in GABAergic neurons derived from iPSCs of patients with PARK2 mutations. These findings suggest that the reduction in the expression level of SST in GABAergic interneurons of PD may, at least partly, lead to complex PD-induced symptoms.
Volume 12(1)
Pages 5
Published 2019-1-18
DOI 10.1186/s13041-019-0426-7
PII 10.1186/s13041-019-0426-7
PMID 30658665
PMC PMC6339354
MeSH Cell Differentiation Cell Line Female GABAergic Neurons / metabolism* GABAergic Neurons / pathology Humans Induced Pluripotent Stem Cells / metabolism* Induced Pluripotent Stem Cells / pathology* Interneurons / metabolism* Interneurons / pathology Male Mutation / genetics* Somatostatin / metabolism* Ubiquitin-Protein Ligases / genetics*
IF 3.449
Human and Animal Cells 201B7(HPS0063)