Morphological changes in perisynaptic astrocytes induced by dopamine neuronal degeneration in the striatum of rats

Liping Sun; Xuefeng Zheng; Yichen Che; Ye Zhang; Ziyun Huang; Linju Jia; Yaofeng Zhu; Wanlong Lei; Guoqing Guo; Chunkui Shao

doi:10.1016/j.heliyon.2024.e27637

Morphological changes in perisynaptic astrocytes induced by dopamine neuronal degeneration in the striatum of rats

Heliyon. 2024 Mar 5;10(6):e27637. doi: 10.1016/j.heliyon.2024.e27637. eCollection 2024 Mar 30.

Authors

Liping Sun¹, Xuefeng Zheng^{2

3}, Yichen Che³, Ye Zhang⁴, Ziyun Huang², Linju Jia², Yaofeng Zhu⁵, Wanlong Lei², Guoqing Guo³, Chunkui Shao¹

Affiliations

¹ Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
² Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
³ Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, China.
⁴ School of Nursing, Sun Yat-Sen University, Guangzhou, China.
⁵ Institute of Medicine, College of Medicine, Jishou University, Jishou, China.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Astrocytes; Dopamine neuronal degeneration; Glutamatergic synapse; Parkinson's disease.