此前的諸多研究顯示，變異Tau蛋白堆積導(dǎo)致的腦神經(jīng)細(xì)胞變性是引發(fā)認(rèn)知癥的主要原因之一,。而日本研究人員經(jīng)動(dòng)物實(shí)驗(yàn)發(fā)現(xiàn),，正常Tau蛋白隨著動(dòng)物年齡增長(zhǎng)也會(huì)出現(xiàn)堆積,。這一發(fā)現(xiàn)將對(duì)認(rèn)知癥病因帶來(lái)一種新認(rèn)識(shí),。
日本理化研究所近日發(fā)布的新聞公報(bào)介紹說(shuō)，Tau蛋白大量存在于中樞神經(jīng)細(xì)胞中,，是構(gòu)成腦神經(jīng)網(wǎng)絡(luò)的神經(jīng)軸突發(fā)揮功能所必需的蛋白質(zhì),。如果這種蛋白發(fā)生變異,，在細(xì)胞內(nèi)形成不溶的凝集,，軸突運(yùn)輸就會(huì)受阻，導(dǎo)致神經(jīng)細(xì)胞死亡,。與這種蛋白相關(guān)的疾病統(tǒng)稱“Tau蛋白病”,，常見(jiàn)的有阿爾茨海默氏癥等,。
在本項(xiàng)研究中,，來(lái)自理化研究所腦科學(xué)綜合研究中心等機(jī)構(gòu)的研究人員將人類Tau蛋白的基因植入實(shí)驗(yàn)鼠,，使實(shí)驗(yàn)鼠腦內(nèi)合成這種蛋白的量是其自身?yè)碛辛康募s４至8倍。
研究人員發(fā)現(xiàn),，這些正常的可溶性蛋白隨著實(shí)驗(yàn)鼠年齡的增長(zhǎng)也會(huì)出現(xiàn)堆積,，并且發(fā)生磷酸化,，進(jìn)而有可能使實(shí)驗(yàn)鼠腦內(nèi)某特定區(qū)域發(fā)生神經(jīng)變性,，導(dǎo)致神經(jīng)活動(dòng)下降,，從而引發(fā)“Tau蛋白病”。研究人員表示,，下一步將研究正常Tau蛋白堆積的原因,。（生物谷Bioon.com）
生物谷推薦原文出處：
Neurobiology of Disease DOI:10.1016/j.nbd.2011.02.002
Differential regional distribution of phosphorylated tau and synapse loss in the nucleus accumbens in tauopathy model mice
Taiki Kambe, Yumiko Motoi, Ran Inoue, Nobuhiko Kojima, Norihiro Tada, Tetsuya Kimura, Naruhiko Sahara, Shunji Yamashita, Tatsuya Mizoroki, Akihiko Takashima, Kohei Shimada, Koichi Ishiguro, Hiroshi Mizuma, Hirotaka Onoe, Yoshikuni Mizuno and Nobutaka Hattor
Tauopathies differ in terms of the brain regions that are affected. In Alzheimer's disease, basal forebrain and hippocampus are mainly involved, while frontotemporal lobar degeneration affects the frontal and temporal lobes and subcortical nuclei including striatum. Over 90% of human cases of tauopathies are sporadic, although the majority of established tau-transgenic mice have had mutations. This prompted us to establish transgenic mice expressing wild-type human tau (Tg601). Old (> 14 months old) Tg601 mice displayed decreased anxiety in the elevated plus maze test and impaired place learning in the Morris water maze test. Immunoblotting of brain tissue identified that soluble tau multimer was increased with aging even though insoluble tau was not observed. In the striatum of old Tg601, the level of AT8- or AT180-positive tau was decreased compared with that of other regions, while PHF-1-positive tau levels remained equal. Phosphorylated tau-positive axonal dilations were present mainly in layers V and VI of the prefrontal cortex. Loss of synaptic dendritic spine and decreased immunohistochemical level of synaptic markers were observed in the nucleus accumbens. In vivo 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography analysis also showed decreased activity exclusively in the nucleus accumbens of living Tg601 mice. In Tg601 mice, the axonal transport defect in the prefrontal cortex–nucleus accumbens pathway may lead to decreased anxiety behavior. Differential distribution of hyperphosphorylated tau may cause region-specific neurodegeneration.
