Behav Brain Res. 2025 Mar 25:115553. doi: 10.1016/j.bbr.2025.115553. Online ahead of print.
ABSTRACT
Anxiety and depression are the most common neuropsychiatric manifestations of Parkinson’s disease (PD) patients. Growing evidence have shown that the dorsal hippocampus (dHIPP) and astrocytes (AS) may be involved in regulating depression and anxiety, but the role and mechanism are still unclear, especially in PD-related depression and anxiety. Unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc) were used to establish the rat model of PD. Behavioral tests and measurement of monoamine levels in the depression and anxiety related brain regions were performed to investigate the effects of chemogenetic activation or inhibition of dHIPP AS on PD-related anxiety and depression. The present results showed that unilateral lesions of the SNc induced anxiety-like and depressive-like behaviors, decreased dopamine (DA) levels in some related brain regions, but did not change the density of glial fibrillary acidic protein-positive AS in the CA1, CA3 and dentate gyrus in rats. Chemogenetic inhibition of dHIPP AS significantly improved anxiety-like and depressive-like behaviors only in the lesioned rats, while chemogenetic activation of dHIPP AS had no effects on anxiety-like and depressive-like behaviors in sham-operated and the lesioned rats. Chemogenetic activation of dHIPP AS only decreased DA level in the ventral hippocampus (vHIPP) in sham-operated rats, while inhibition of dHIPP AS increased 5-hydroxytryptamine (5-HT) levels in the medial prefrontal cortex (mPFC) and vHIPP in sham-operated rats and also in the amygdala, mPFC, lateral habenula, dHIPP and vHIPP in the lesioned rats. These results indicate that chemogenetic inhibition of dHIPP AS improves the anxiety-like and depressive-like behaviors in the lesioned rats through the changes in monoamine in some brain regions.
PMID:40147794 | DOI:10.1016/j.bbr.2025.115553
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