ArticleNPJ Parkinson's disease2025
Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype.
Article in NPJ Parkinson's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- A serotonergic perspective on depression in Parkinson's disease: From synaptic disruption to network failure.Neural regeneration research · 2026Article
- Role of α-Synuclein in the Prefrontal Cortex: From Physiological Synaptic Modulation to Synaptic Failure in Parkinson's Disease.Biomedicines · 2026Review
- New insights into synaptic vesicle dysfunction in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- GDNF signaling modulation by Akkermansia muciniphila ameliorates constipation-depression comorbidity in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- A molecular convergence in the triad of parkinson's disease, depressive disorder and gut health is revealed by the inflammation-miRNA axis.Journal of neuroinflammation · 2025Article
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Authors and funding
11 authors.
Funding
Abstract
Anxiety and depression are common in Parkinson's disease (PD), affecting quality of life. Aggregates of α-synuclein (α-Syn) are found in serotonergic (5-HT) raphe nuclei early in the disease, but their relationship to brain changes is unclear. We investigated synaptic plasticity, neuronal activity, and functional magnetic resonance imaging (fMRI)-based brain connectivity in a PD-like mouse model with depressive phenotype. AAV-induced human α-Syn accumulation in raphe 5-HT neurons causes progressive synaptic pathology in interconnected brain regions. This is marked by lower MAP-2, PSD95 and higher SV2A, VAMP2, which are key to synaptic structure and function, as confirmed in human brain tissue samples. Abnormalities in Egr-1-dependent neuronal activity and region-specific differences in resting-state functional brain activity were also detected eight weeks post-AAV infusion, before neurodegeneration. This provides evidence for synaptic and fMRI markers associated with α-Syn pathology in emotional brain circuits, and has translational importance for identifying PD patients at risk for depression.
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Registered trials
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