12月12日在線發(fā)表在國際著名期刊《自然—神經(jīng)科學(xué)》(Nature Neuroscience)上，浙江大學(xué)醫(yī)學(xué)院神經(jīng)科學(xué)研究所李曉明教授課題組的一項研究結(jié)果"Neuregulin 1 regulates excitability of fast-spiking neurons through Kv1.1 and acts in epilepsy"稱Neuregulin1/ErbB4是精神分裂癥的易感基因,。
俗稱“羊角風(fēng)”,、“羊癇風(fēng)” 的癲癇，醫(yī)學(xué)界公認(rèn)這是大腦神經(jīng)元突發(fā)性異常放電造成的,。是什么導(dǎo)致神經(jīng)元的放電“剎不住車”,？李曉明教授課題組的這項研究為此提供了新的回答。
癲癇是人群中發(fā)病率較高的一種疾病,，影響總?cè)丝诘拇蠹s1%,，中國約有一千萬患者，目前,，經(jīng)過現(xiàn)有的抗癲癇藥物治療,，仍有大約30%的患者不能控制。對于藥物不能控制的癲癇目前多采取手術(shù)治療,，而適合手術(shù)的患者只占一小部分,。因此，尋找有效和安全的治療藥物是生物醫(yī)學(xué)重要的目標(biāo)之一,。
現(xiàn)有的大量研究表明,，Neuregulin1/ErbB4是精神分裂癥的易感基因，李曉明教授的課題組在研究這對基因的過程中,，“意外”地發(fā)現(xiàn)它們對抑制性神經(jīng)元興奮性有調(diào)節(jié)作用,。“這令我們很興奮。”李曉明介紹,，大腦皮層神經(jīng)元主要由興奮性神經(jīng)元和抑制性神經(jīng)元組成,，就像“油門”和“剎車”,，雙方在正常情況下保持平衡狀態(tài)。如果“剎車”功能受損,，大腦內(nèi)興奮性和抑制性神經(jīng)環(huán)路就會失去平衡,，引起大腦異常放電，導(dǎo)致癲癇發(fā)生,。
接下來的研究表明,，抑制性神經(jīng)元上的ErbB4受體可以影響神經(jīng)元的活性。神經(jīng)調(diào)節(jié)素Neuregulin1通過結(jié)合ErbB4受體,，增加“剎車”的活性,。“如果ErbB4受體異常，很可能會導(dǎo)致‘剎車’失靈,。”李曉明介紹,。
論文第一作者，課題組成員之一李可心博士說,，這一研究不但在基因敲除小鼠實驗上進(jìn)行了驗證,，還由本論文的共同作者、浙江大學(xué)醫(yī)學(xué)院附屬第二醫(yī)院神經(jīng)外科的張建明和朱君明主任醫(yī)師在癲癇患者組織標(biāo)本中得到了驗證,。“NRG和它的受體ErbB4可能是癲癇的易感基因,，這不僅為探索癲癇抑制藥物的新型有效分子“靶標(biāo)”提供了研究方向，而且還為治療以神經(jīng)元興奮性改變?yōu)榛A(chǔ)的腦疾病的新藥篩選提供了研究基礎(chǔ),。”李曉明說,。（生物谷bioon.com）
延伸閱讀：
長時間用手機可能誘發(fā)癲癇
Steroid：青陽參對難治性癲癇有效
葛蘭素癲癇藥物獲歐盟上市批準(zhǔn)
doi:10.1038/nn.3006
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Neuregulin 1 regulates excitability of fast-spiking neurons through Kv1.1 and acts in epilepsy
Ke-Xin Li; Ying-Mei Lu; Zheng-Hao Xu; Jing Zhang; Jun-Ming Zhu; Jian-Ming Zhang; Shu-Xia Cao; Xiao-Juan Chen; Zhong Chen; Jian-Hong Luo; Shumin Duan; Xiao-Ming Li
Dysfunction of fast-spiking, parvalbumin-positive (FS-PV) interneurons is implicated in the pathogenesis of epilepsy. ErbB4, a key Neuregulin 1 (NRG1) receptor, is mainly expressed in this type of interneurons, and recent studies suggest that parvalbumin interneurons are a major target of NRG1-ErbB4 signaling in adult brain. Thus, we hypothesized that downregulation of NRG1-ErbB4 signaling in FS-PV interneurons is involved in epilepsy. We found that NRG1, through its receptor ErbB4, increased the intrinsic excitability of FS-PV interneurons. This effect was mediated by increasing the near-threshold responsiveness and decreasing the voltage threshold for action potentials through Kv1.1, a voltage-gated potassium channel. Furthermore, mice with specific deletion of ErbB4 in parvalbumin interneurons were more susceptible to pentylenetetrazole- and pilocarpine-induced models of epilepsy. Exogenous NRG1 delayed the onset of seizures and decreased their incidence and stage. Moreover, expression of ErbB4, but not ErbB2, was downregulated in human epileptogenic tissue. Together, our findings suggest that NRG1–ErbB4 signaling contributes to human epilepsy through regulating the excitability of FS-PV interneurons. ErbB4 may be a new target for anticonvulsant drugs in epilepsy.
