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J Neurophysiol. 2016 Aug 1;116(2):448-55. doi: 10.1152/jn.00229.2016. Epub 2016 May 4.

Role of Fyn-mediated NMDA receptor function in prediabetic neuropathy in mice.

Author information

1
Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People's Republic of China.
2
Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People's Republic of China myzhang324@sina.com.

Abstract

Diabetic neuropathy is a common complication of diabetes. This study evaluated the role of Fyn kinase and N-methyl-d-aspartate receptors (NMDARs) in the spinal cord in diabetic neuropathy using an animal model of high-fat diet-induced prediabetes. We found that prediabetic wild-type mice exhibited tactile allodynia and thermal hypoalgesia after a 16-wk high-fat diet, relative to normal diet-fed wild-type mice. Furthermore, prediabetic wild-type mice exhibited increased tactile allodynia and thermal hypoalgesia at 24 wk relative to 16 wk. Such phenomena were correlated with increased expression and activation of NR2B subunit of NMDARs, as well as Fyn-NR2B interaction in the spinal cord. Fyn(-/-) mice developed prediabetes after 16-wk high-fat diet treatment and exhibited thermal hypoalgesia, without showing tactile allodynia or altered expression and activation of NR2B subunit, relative to normal diet-fed Fyn(-/-) mice. Finally, intrathecal administrations of Ro 25-6981 (selective NR2B subunit-containing NMDAR antagonist) dose-dependently alleviated tactile allodynia, but not thermal hypoalgesia, at 16 and 24 wk in prediabetic wild-type mice. Our results suggested that Fyn-mediated NR2B signaling plays a critical role in regulation of prediabetic neuropathy and that the increased expression/function of NR2B subunit-containing NMDARs may contribute to the progression of neuropathy in type 2 diabetes.

KEYWORDS:

Fyn kinase; NMDA; neuropathic pain; prediabetes; spinal cord

PMID:
27146985
PMCID:
PMC4978791
DOI:
10.1152/jn.00229.2016
[Indexed for MEDLINE]
Free PMC Article

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