■以前显示星形胶质细胞的典型功能被帕金森氏病(PD)破坏,积极调节突触神经传递。然而,多巴胺(DA)神经元变性后,纹状体中包裹谷氨酸能突触的星形胶质细胞的形态变化尚不清楚。
■我们使用了一系列方法,包括6-羟基多巴胺(6OHDA)诱导的PD模型,以及免疫组织化学等技术,西方印迹,免疫荧光和免疫电子显微镜(IEM)深入研究DA神经元变性对突触周围星形胶质细胞形态属性的影响。
■我们的发现表明,由于DA神经元变性,胶质纤维酸性蛋白(GFAP)星形胶质细胞密度显着升高,纹状体内GFAP蛋白表达上调,与扩大相吻合,伸长率,星形胶质细胞突起增厚。然而,谷氨酸转运蛋白1(GLT1)和谷氨酰胺合成酶(GS)的表达水平,与谷氨酸-谷氨酰胺循环有关,显着减少。双重免疫荧光和IEM结果表明,不同比例的囊泡谷氨酸转运体1(VGlut1)和囊泡谷氨酸转运体2(VGlut2)末端被星形胶质细胞包裹。此外,DA神经元变性增加了纹状体中GFAP星形胶质细胞包裹的VGlut1和VGlut2末端的百分比和面积。此外,我们注意到DA神经元变性增加了星形胶质细胞包裹的VGlut1+和VGlut2+轴突突触的百分比,但对轴突突触没有影响.
■因此,包裹纹状体谷氨酸能突触的突触周围星形胶质细胞在DA神经元变性后表现出实质性的形态和功能改变,使其成为PD治疗干预的潜在目标。
UNASSIGNED: The typical functionality of astrocytes was previously shown to be disrupted by Parkinson\'s disease (PD), which actively regulates synaptic neurotransmission. However, the morphological changes in astrocytes wrapping glutamatergic synapses in the striatum after dopamine (DA) neuronal degeneration is unclear.
UNASSIGNED: We utilized a range of methodologies, encompassing the 6-hydroxydopamine (6OHDA)-induced PD model, as well as techniques such as immunohistochemistry, Western blotting, immunofluorescence and immunoelectron microscopy (IEM) to delve into the consequences of DA neuronal degeneration on the morphological attributes of perisynaptic astrocytes.
UNASSIGNED: Our findings demonstrated a notable rise in glial fibrillary acidic protein (GFAP) + astrocyte density and an upregulation in GFAP protein expression within the striatum due to DA neuronal degeneration, coincided with the enlargement, elongation, and thickening of astrocyte protuberances. However, the expression levels of glutamate transporter 1 (GLT1) and glutamine synthetase (GS), which are related to glutamate-glutamine cycle, were significantly reduced. Double immunofluorescence and IEM results indicated that different proportions of vesicular glutamate transporter 1 (VGlut1)+ and vesicular glutamate transporter 2 (VGlut2) + terminals were wrapped by astrocytes. Additionally, DA neuronal degeneration increased the percentage and area of VGlut1+ and VGlut2+ terminals wrapped by GFAP + astrocytes in the striatum. Furthermore, we noted that DA neuronal degeneration increased the percentage of VGlut1+ and VGlut2+ axo-spinous synapses wrapped by astrocytes but had no effect on axo-dendritic synapses.
UNASSIGNED: Hence, perisynaptic astrocytes wrapping striatal glutamatergic synapses exhibit substantial morphological and functional alterations following DA neuronal degeneration making them a potential target for therapeutic interventions in PD.