阿爾茨海默癥的特點(diǎn)是沉積的老年斑塊和逐步嚴(yán)重的癡呆癥狀。然而,，目前這種斑塊的沉積與神經(jīng)系統(tǒng)發(fā)生故障的分子機(jī)制尚且未知。
利用轉(zhuǎn)基因小鼠模型聯(lián)同多光子成像技術(shù),，Kuchibhotla等人利用基因編碼的鈣離子敏感蛋白YC 3.6,，在體內(nèi)研究了一些神經(jīng)突起和神經(jīng)刺體內(nèi)的神經(jīng)元鈣。相關(guān)論文發(fā)表在7月31日的《神經(jīng)元》（Neuron）雜志上,。
定量的成像結(jié)果顯示,，隨著大腦皮層斑塊的出現(xiàn)，在APP小鼠神經(jīng)突起中鈣含量超過(guò)20％,；相比之下,，在野生型、PS1突變小鼠或年輕的APP小鼠中的鈣含量少于5％,。鈣含量高與斑塊有關(guān),。接下來(lái)的研究結(jié)果表明，相應(yīng)的棘-樹突觸中鈣區(qū)域在減少,，同時(shí)神經(jīng)元形態(tài)發(fā)生變形,，這部分是由鈣調(diào)磷酸酶引起的變化。
總之，新的研究數(shù)據(jù)表明,，老年斑塊損害了體內(nèi)神經(jīng)元的鈣穩(wěn)態(tài),，從而導(dǎo)致神經(jīng)元網(wǎng)絡(luò)結(jié)構(gòu)與功能的破壞。（生物谷Bioon.com）
生物谷推薦原始出處：
Neuron,，Vol 59, 214-225, 31 July 2008,，Kishore V. Kuchibhotla, Brian J. Bacskai
Aβ Plaques Lead to Aberrant Regulation of Calcium Homeostasis In Vivo Resulting in Structural and Functional Disruption of Neuronal Networks
Kishore V. Kuchibhotla,1,2 Samuel T. Goldman,1 Carli R. Lattarulo,1 Hai-Yan Wu,1 Bradley T. Hyman,1 and Brian J. Bacskai1,
1 Massachusetts General Hospital, Department of Neurology/Alzheimer's Disease Research Laboratory, 114 16th Street, Charlestown, MA 02129, USA
2 Program in Biophysics, Harvard University, Cambridge, MA 02138, USA
Corresponding author
Brian J. Bacskai
Summary
Alzheimer's disease is characterized by the deposition of senile plaques and progressive dementia. The molecular mechanisms that couple plaque deposition to neural system failure, however, are unknown. Using transgenic mouse models of AD together with multiphoton imaging, we measured neuronal calcium in individual neurites and spines in vivo using the genetically encoded calcium indicator Yellow Cameleon 3.6. Quantitative imaging revealed elevated [Ca2+]i (calcium overload) in ～20% of neurites in APP mice with cortical plaques, compared to less than 5% in wild-type mice, PS1 mutant mice, or young APP mice (animals without cortical plaques). Calcium overload depended on the existence and proximity to plaques. The downstream consequences included the loss of spinodendritic calcium compartmentalization (critical for synaptic integration) and a distortion of neuritic morphologies mediated, in part, by the phosphatase calcineurin. Together, these data demonstrate that senile plaques impair neuritic calcium homeostasis in vivo and result in the structural and functional disruption of neuronal networks.
