A comparison of the impact on neuronal transcriptome and cognition of rAAV5 transduction with three different doses in the mouse hippocampus.
anxiety
hippocampus
learning and memory
rAAV
transcriptome
Journal
Frontiers in molecular neuroscience
ISSN: 1662-5099
Titre abrégé: Front Mol Neurosci
Pays: Switzerland
ID NLM: 101477914
Informations de publication
Date de publication:
2023
2023
Historique:
received:
28
03
2023
accepted:
20
06
2023
medline:
31
7
2023
pubmed:
31
7
2023
entrez:
31
7
2023
Statut:
epublish
Résumé
Recombinant adeno-associated viruses (rAAVs) are widely used in genetic therapeutics. AAV5 has shown superior transduction efficiency, targeting neurons and glial cells in primate brains. Nonetheless, the comprehensive impact of AAV5 transduction on molecular and behavioral alterations remains unexplored. This study focuses on evaluating the effects of AAV5 transduction in the hippocampus, a critical region for memory formation and emotional processes. In this experiment, fluorescence-activated cell sorting (FACS) was utilized to isolate the mCherry-labeled pyramidal neurons in the hippocampus of CaMkIIα-cre mice following three different doses rAAV5-mCherry infusion after 3 weeks, which were then subjected to RNA sequencing (RNA-seq) to assess gene expression profiles. The cytokines concentration, mRNA expression, and glial response in hippocampi were confirmed by ELASA, digital droplet PCR and immunohistochemistry respectively. Locomotion and anxiety-like behaviors were elevated by Open Field Test and Elevated Plus Maze Test, while the Y-Maze were used to assessed spatial working memory. Recognition memory and fear responses were examined by the Novel Object Recognition Test and Fear Conditioning Test, respectively. We found that 2.88 × 10 Our findings highlight the detrimental impact of high-dose administration compared to median-dose or low-dose, resulting in increased neural vulnerability and impaired memory. Therefore, when considering the expression effectiveness of exogenous genes, it is crucial to also take potential side effects into account in clinical settings. However, the precise molecular mechanisms underlying these drawbacks of high-dose rAAV5-mCherry still require further investigation in future studies.
Identifiants
pubmed: 37520430
doi: 10.3389/fnmol.2023.1195327
pmc: PMC10375024
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1195327Informations de copyright
Copyright © 2023 Liu, Wang, Hu, Li, Wu, Li, Li, Li, Yang, Gao and Chen.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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