Enteric Glial Dysfunction Evoked by Apolipoprotein E Deficiency Contributes to Delayed Gastric Emptying

Seiichiro Fukuhara, Tatsuhiro Masaoka, Soraya Nishimura, Masaya Nakamura, Juntaro Matsuzaki, Hitoshi Tsugawa, Sawako Miyoshi, Hideki Mori, Satoshi Kawase, Shinsuke Shibata, Hideyuki Okano, Takanori Kanai, Hidekazu Suzuki

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background and Aim: Diabetes is the main cause of gastroparesis accompanying decreased neuronal nitric oxide synthase (nNOS) in myenteric ganglia of the stomach. Decreased nNOS expression in the stomach also results from defects in apolipoprotein E (ApoE), which is secreted by astrocytes and has neuroprotective effects on the central nervous system. However, the roles of ApoE and enteric glial cells on gastric motility are uncertain. In this study, ApoE and enteric glial cell alterations in gastroparesis were investigated. Methods: Type 2 diabetic (db/db) mice and ApoE-knockout mice were analyzed. Gastric emptying was measured using the 13C acetic acid breath test. Expression levels of the pan-neuronal marker, protein gene product 9.5 (PGP 9.5), and glial marker, glial fibrillary acidic protein (GFAP) were examined by immunohistochemistry. Neural stem cells (NSCs) were injected into the gastric antral wall of ApoE-knockout mice. Results: Delayed gastric emptying was observed in 27% of db/db mice with significant decreases in serum ApoE levels and GFAP expression in the gastric antrum. Gastric emptying was also delayed in ApoE-knockout mice, with a significant decrease in GFAP expression, but no change in PGP 9.5 expression. Transplantation of NSCs improved gastric emptying in ApoE-knockout mice through supplementation of GFAP-positive cells. Conclusions: Our results suggest that decreased enteric glial cells in ApoE-knockout mice are crucial for development of delayed gastric emptying, and NSC transplantation is effective in restoring myenteric ganglia and gastric motility.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalDigestive Diseases and Sciences
DOIs
Publication statusAccepted/In press - 2017 Nov 2

Keywords

  • Apolipoprotein E
  • Enteric glial cells
  • Gastroparesis
  • Neural stem cells

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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