Reduced expression of somatostatin in GABAergic interneurons derived from induced pluripotent stem cells of patients with parkin mutations

Chizuru Iwasawa, Naoko Kuzumaki, Yukari Suda, Reiko Kagawa, Yuko Oka, Nobutaka Hattori, Hideyuki Okano, Minoru Narita

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Article number5
JournalMolecular Brain
Volume12
Issue number1
DOIs
Publication statusPublished - 2019 Jan 18

Fingerprint

Induced Pluripotent Stem Cells
Interneurons
Somatostatin
Parkinson Disease
GABAergic Neurons
Mutation
GABA Modulators
Constipation
Prosencephalon
gamma-Aminobutyric Acid
Cerebrospinal Fluid
Dementia
Depression
Messenger RNA
Genes

Keywords

  • GABA
  • iPSCs
  • Parkinson's disease
  • Somatostatin

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Reduced expression of somatostatin in GABAergic interneurons derived from induced pluripotent stem cells of patients with parkin mutations. / Iwasawa, Chizuru; Kuzumaki, Naoko; Suda, Yukari; Kagawa, Reiko; Oka, Yuko; Hattori, Nobutaka; Okano, Hideyuki; Narita, Minoru.

In: Molecular Brain, Vol. 12, No. 1, 5, 18.01.2019.

Research output: Contribution to journalArticle

Iwasawa, Chizuru ; Kuzumaki, Naoko ; Suda, Yukari ; Kagawa, Reiko ; Oka, Yuko ; Hattori, Nobutaka ; Okano, Hideyuki ; Narita, Minoru. / Reduced expression of somatostatin in GABAergic interneurons derived from induced pluripotent stem cells of patients with parkin mutations. In: Molecular Brain. 2019 ; Vol. 12, No. 1.
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