Secretoneurin promotes neuroprotection and neuronal plasticity via the Jak2/Stat3 pathway in murine models of stroke

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Title:	Secretoneurin promotes neuroprotection and neuronal plasticity via the Jak2/Stat3 pathway in murine models of stroke
Authors:	徐偉成(Woei-Cherng Shyu);林欣榮(Shinn-Zong Lin);(Ming-Fu Chiang);陳德誠(Der-Cherng Chen);(Ching-Yuan Su);王孝榮(Hsiao-Jung Wang);(Ren-Shyan Liu);蔡長海(Chang-Hai Tsai);李鴻(Hung Li)
Contributors:	醫學院免疫學研究所;中國附醫神經部
Date:	2008-01
Issue Date:	2010-09-27 15:42:45 (UTC+8)
Publisher:	American Society for Clinical Investigation
Abstract:	Secretoneurin (SN), a neuropeptide derived from secretogranin II, promotes neurite outgrowth of immature cerebellar granule cells. SN also aids in the growth and repair of neuronal tissue, although the precise mechanisms underlying the promotion of brain tissue neuroprotection and plasticity by SN are not understood. Here, in a rat model of stroke and in ischemic human brain tissue, SN was markedly upregulated in both neurons and endothelial cells. SN-mediated neuroprotection rescued primary cortical cell cultures from oxygen/glucose deprivation. SN also induced expression of the antiapoptotic proteins Bcl-2 and Bcl-xL through the Jak2/Stat3 pathway and inhibited apoptosis by blocking caspase-3 activation. In addition, rats with occluded right middle cerebral arteries showed less cerebral infarction, improved motor performance, and increased brain metabolic activity following i.v. administration of SN. Furthermore, SN injection enhanced stem cell targeting to the injured brain in mice and promoted the formation of new blood vessels to increase local cortical blood flow in the ischemic hemisphere. Both in vitro and in vivo, SN not only promoted neuroprotection, but also enhanced neurogenesis and angiogenesis. Our results demonstrate that SN acts directly on neurons after hypoxia and ischemic insult to further their survival by activating the Jak2/Stat3 pathway.
Relation:	JOURNAL OF CLINICAL INVESTIGATION 118(1):133-148
Appears in Collections:	[Graduate Institute of Immunology] Journal articles

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