The Aggregation of α-Synuclein in the Dorsomedial Striatum Significantly Impairs Cognitive Flexibility in Parkinson’s Disease Mice

Autor: Jing Chen, Yifang Liu, Mingyu Su, Yaoyu Sun, Chenkai Liu, Sihan Sun, Ting Wang, Chuanxi Tang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Biomedicines, Vol 12, Iss 8, p 1634 (2024)
Druh dokumentu: article
ISSN: 2227-9059
DOI: 10.3390/biomedicines12081634
Popis: This study focused on α-synuclein (α-syn) aggregation in the dorsomedial striatum (DMS) so as to investigate its role in the cognitive flexibility of Parkinson’s disease (PD). Here, we investigated the cognitive flexibility by assessing reversal learning abilities in MPTP-induced subacute PD model mice and in C57BL/6J mice with α-syn aggregation in the DMS induced by adenovirus (AAV-SNCA) injection, followed by an analysis of the target protein’s expression and distribution. PD mice exhibited impairments in reversal learning, positively correlated with the expression of phosphorylated α-syn in the DMS. Furthermore, the mice in the AAV-SNCA group exhibited reversal learning deficits and a reduction in acetylcholine levels, accompanied by protein alterations within the DMS. Notably, the administration of a muscarinic receptor 1 (M1R) agonist was able to alleviate the aforementioned phenomenon. These findings suggest that the impaired cognitive flexibility in PD may be attributed to the diminished activation of acetylcholine to M1R caused by α-syn aggregation.
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