Regulation of gene expression by viral vectors is an effective method for researchers to explore the function of gene products in a target tissue. The choroid plexus (CP) is an important target for gene therapy of neuropsychiatric diseases such as Alzheimer's disease and major depressive disorder. However, viral tropism in CP has not been well studied as a result of limited viral vector applications. To identify CP-specific viral vectors, we intracerebroventricularly administered six different serotypes of adeno-associated virus (AAV) vectors (AAV2/1, AAV2/5, AAV2/8, AAV2/9, AAV2-BR1, and AAV2-PHP.eB) and lentivirus in adult mice. Tropism in CP was compared among these viruses. We found that AAV2/5 and AAV2/8 displayed remarkable infections in CP, while AAV2/1 infected both ependymal cells and cells in the CP. Except for the low infection intensity of AAV2/9 and lentivirus in the CP, no infection intensity was found for CP tissues injected with AAV2-BR1 or AAV2-PHP.eB. Green fluorescence protein expression in the CP after AAV2/5 infection was confirmed by Western blotting. AAV2/5-mediated tropism in epithelial cells of the CP was verified by immunostaining with transthyretin. In this study, we identified for the first time that serotype-specific AAVs 5 and 8 may be robust research tools for intracerebroventricular gene delivery.

The proportion of major depressive disorder (MDD) patients around the world has increased remarkably. Although many studies of MDD have been conducted based on classic hypotheses, like alteration of the hypothalamic–pituitary–adrenal axis or monoamine neurotransmitters, the mechanisms underlying MDD remain unclear. Aiming to further investigate the mechanisms of MDD, liquid chromatography–tandem mass spectrometry was employed to measure target metabolites in the hippocampus (HIPPO) of chronic social defeat stress model mice. Compared with control mice, stress‐susceptible mice showed a reduction of 5‐hydroxyindoleacetic acid and kynurenic acid in the tryptophan pathway, and an increased level of dopamine in the catecholamine pathway, while stress‐resilient mice displayed a reduction of 5‐hydroxytryptamine in the tryptophan pathway. The altered levels of key molecules related to the tryptophan or dopamine metabolic pathways were validated by real‐time quantitative polymerase chain reaction or western blotting. Comparative analysis with previous targeted metabolomics results in the prefrontal cortex (PFC) of chronic social defeat stress mice revealed that the altered metabolites manifested in specific brain areas, and only the dopamine metabolic pathway was perturbed in both the HIPPO and PFC after stress. Additionally, correlation analysis validated that levels of kynurenic acid in the HIPPO, along with glutamic acid, L‐3, 4‐dihydroxyphenylalanine, and vanillylmandelic acid in the PFC, were correlated with depression‐like behaviors. This study provides a unique perspective on the potential molecular mechanisms of stress susceptibility and stress resilience.

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