Viral-mediated increased hippocampal neurogranin modulate synapses at one month in a rat model of controlled cortical impact

Autor: Sarah E. Svirsky, Jeremy Henchir, Madison Parry, Erik Holets, Ting Zhang, George K. Gittes, Shaun W. Carlson, C. Edward Dixon
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Scientific Reports, Vol 14, Iss 1, Pp 1-16 (2024)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-024-77682-2
Popis: Abstract Reductions of neurogranin (Ng), a calcium-sensitive calmodulin-binding protein, result in significant impairment across various hippocampal-dependent learning and memory tasks. Conversely, increasing levels of Ng facilitates synaptic plasticity, increases synaptogenesis and boosts cognitive abilities. Controlled cortical impact (CCI), an experimental traumatic brain injury (TBI) model, results in significantly reduced hippocampal Ng protein expression up to 4 weeks post-injury, supporting a strategy to increase Ng to improve function. In this study, hippocampal Ng expression was increased in adult, male Sham and CCI injured animals using intraparenchymal injection of adeno-associated virus (AAV) 30 min post-injury, thereby also affording the ability to differentiate endogenous and exogenous Ng. At 4 weeks, molecular, anatomical, and behavioral measures of synaptic plasticity were evaluated to determine the therapeutic potential of Ng modulation post-TBI. Increasing Ng had a TBI-dependent effect on hippocampal expression of synaptic proteins and dendritic spine morphology. Increasing Ng did not improve behavior across all outcomes in both Sham and CCI groups at the 4 week time-point. Overall, increasing Ng expression modulated protein expression and dendritic spine morphology, but exerted limited functional benefit after CCI. This study furthers our understanding of Ng, and mechanisms of cognitive dysfunction within the synapse sub-acutely after TBI.
Databáze: Directory of Open Access Journals
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