GDNF attenuates a-synuclein aggregation-induced damage to VTA-NAc dopaminergic transmission and alleviates depression-like behaviors in mice.

ABSTRACT: Dopamine (DA) transmission from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) is strongly associated with depression in Parkinson's disease (PD). Decreased DA levels due to alpha-synuclein (α-syn) aggregation have been underappreciated in relation to depression in PD. This study investigated the role of VTA-related α-syn aggregation in depression of PD, and whether gial cell line-derived neurotrophic factor (GDNF) can inhibit α-syn aggregation to improve symptoms. Here, α-syn aggregation and GDNF overexpression were induced in the VTA of 8-week-old male mice (C57BL/6J, DAT-cre, D2-cre) using adeno-associated viruses, combined with a cis-tracer virus as well as a chemogenetic virus. Behavioral tests, immunofluorescence (IF), western blot (WB), and enzyme-linked immunosorbe

SUBMITTER: Chen J 

PROVIDER: S-EPMC12370956 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature