Reconstruction of neuronal network in neurodegenerative disorders

在神经元网络的形成过程中，单个神经元的形态起着重要的作用。早老素1（PS1）的突变与家族性阿尔茨海默病（AD）高度相关。我们使用SH-SY 5 Y细胞研究了PS1对神经元形态的影响。显性负性PS1的过度表达诱导神经突形成的损害，而野生型和AD相关的突变体PS1没有改变细胞形态与天然细胞相比。肌动蛋白细胞凋亡相关蛋白，如Wiskott-Aldrich综合征蛋白（N-WASP），只在表达显性阴性PS1的细胞中减少。因此，PS1可能参与了SH-SY 5 Y细胞的轴突发生和形态学改变。此外，我们还研究了肌动蛋白相关蛋白N-WASP、WASP家族verprolin-homologous protein（WAVE）在大鼠生后发育过程中的表达水平和分布。这些因素在发育过程中逐渐增加，并似乎存在于发育过程中。 ...更多信息 突触丰富的区域。因此，N-WASP和WAVE可能通过调节肌动蛋白细胞骨架参与正常脑发育和突触可塑性。大脑中动脉（MCA）闭塞和再灌注导致行为功能障碍，神经网络大量受损。我们研究了移植大鼠培养的小胶质细胞、小鼠胚胎干细胞（ES）或ES细胞衍生的神经元样细胞（ES-N）对缺血大鼠行为功能的影响。通过移植，局灶性缺血诱导的行为功能障碍被显著抑制。行为功能障碍的有效改善可能是由于外源性小胶质细胞的神经保护作用以及ES和ES-N细胞移植恢复多巴胺能神经元功能所致。为了研究帕金森氏病（PD）的移植策略，我们评估了纹状体（ST）和黑质（SN）或ST和丘脑底核（STN）中的双移植是否会诱导6-羟基多巴胺损伤大鼠的功能恢复。将小鼠ES-N移植到ST中可显著减少药物诱导的旋转，但单独移植ES-N或SN则无此作用。双移植在恢复旋转行为方面也有效。这些结果表明，ST的参与和作为移植的地方和ES-N的数量是影响疗效的重要因素。DJ-1最近被证明是家族性PD，PARK 7发病的原因。使用6-羟基多巴胺损伤的大鼠，我们进一步发现同时和/或后注射重组野生型而非突变型人DJ-1具有神经保护作用。少

In the formation of neuronal network, morphology of individual neuron plays an important role. Mutations in presenilin 1 (PS1) are highly related to familial Alzheimer's disease (AD). We examined the effects of PS1 on neuronal morphology using SH-SY5Y cells. Overexpression of dominant-negative PS1 induced impairment of neurite formation, while those of wild-type and AD-related mutant PS1 did not change cellular morphology compared with native cells. Actin cytoskeleton-related proteins, such as Wiskott-Aldrich syndrome protein (N-WASP), were decreased only in cells expressing dominant-negative PS1. Therefore, PS1 may be involved in neuritogenesis and morphological change in SH-SY5Y cells. Furthermore, we examined the expression levels and distributions of actin cytoskeleton-related proteins, such as N-WASP, WASP family verprolin-homologous protein (WAVE) in the rat brain during postnatal development. These factors were progressively increased during development, and seemed to exist in t … More he synapse-rich areas. Thus, N-WASP and WAVE may participate in normal brain development and synaptic plasticity by regulating the actin cytoskeleton. Occlusion of the middle cerebral artery (MCA) and reperfusion caused behavioral dysfunction with massive damage of neuronal network. We examined the effects of transplantation of rat cultured microglia, mouse embryonic stem (ES) cells or ES cell-derived neuron-like (ES-N) cells on behavioral function in ischemic rats. By the transplantation, focal ischemia-induced behavioral dysfunction was significantly inhibited. The effective improvement of behavioral dysfunction may be due to the neuroprotective effect of exogenous microglia and the recovery of dopaminergic neuronal function by the transplantation of ES and ES-N cells. To investigate a transplantation strategy for Parkinson's disease (PD), we assessed whether double-transplants in the striatum (ST) and substantia nigra (SN), or ST and subthalamic nucleus (STN) induce functional recovery in 6-hydroxydopamine-lesioned rats. Drug-induced rotation was significantly reduced by transplantation of mouse ES-N into the ST, but not the STN or SN alone. Double-transplantation was also effective at recovering rotational behavior. These results suggest that both the involvement of ST and as a place of transplantation and the number of ES-N are essential factors for efficacy on hemiparkinsonian behaviors. DJ-1 has recently been shown to be responsible for onset of familial PD, PARK7. Using 6-hydroxydopamine-lesioned rats, we further found that the simultaneous and/or post injection of recombinant wild type, but not mutant human DJ-1 had neuroprotective effect. Less