Ameliorating Effect of Hypothalamic Brain-Derived Neurotrophic Factor Against Impaired Glucose Metabolism After Cerebral Ischemic Stress in Mice

• Harada Shinichi

  Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, Japan

• Fujita-Hamabe Wakako

  Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, Japan

• Tokuyama Shogo

  Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, Japan

Abstract

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has potent neuroprotective effects against brain injury. We recently reported that glucose intolerance/hyperglycemia could be induced by ischemic stress (i.e., post-ischemic glucose intolerance) following ischemic neuronal damage. Therefore, the aim of this study was to determine the effects of BDNF on the development of post-ischemic glucose intolerance and ischemic neuronal damage. Male ddY mice were subjected to middle cerebral artery occlusion (MCAO) for 2 h. On day 1, the expression levels of BDNF were significantly decreased in the cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor, a BDNF receptor, decreased in the hypothalamus and liver and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex. Intrahypothalamic administration of BDNF (50 ng/mouse) suppressed the development of post-ischemic glucose intolerance on day 1 and neuronal damage on day 3 after MCAO. In the liver and skeletal muscle, the expression levels of insulin receptors decreased, while gluconeogenic enzyme levels increased on day 1 after MCAO. These changes completely recovered to normal levels in the presence of BDNF. These results indicate that regulation of post-ischemic glucose intolerance by BDNF may suppress ischemic neuronal damage.

Journal

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 118 (1), 109-116, 2012

  The Japanese Pharmacological Society

Keywords

• cerebral ischemic stress
• brain-derived neurotrophic factor
• insulin receptor
• gluconeogenesis
• middle cerebral artery occlusion

Details

• CRID: 1390282680158187264
• NII Article ID: 10030454384
• NII Book ID: AA11806667
• DOI: 10.1254/jphs.11164fp
• COI: 1:CAS:528:DC%2BC38Xhs1ygsbo%3D
• ISSN: 13478648
• ISSN: 13478613
• NDL BIB ID: 023388062
• PubMed: 22198007
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I023388062
• Web Site: https://search.jamas.or.jp/link/ui/2012144269
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed