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- W2906615611 abstract "Adolescence represents a critical period of neurodevelopment, defined by structural and synaptic pruning within the prefrontal cortex. While characteristic of typical development, this structural instability may open a window of vulnerability to developing neuropsychiatric disorders, including depression. Thus, therapeutic interventions that support or expedite neural remodeling in adolescence may be advantageous. Here, we inhibited the neuronally-expressed cytoskeletal regulatory factor Rho-kinase (ROCK), focusing primarily on the clinically-viable ROCK inhibitor fasudil. ROCK inhibition had rapid antidepressant-like effects in adolescent mice, and its efficacy was comparable to ketamine and fluoxetine. It also modified levels of the antidepressant-related signaling factors, tropomyosin/tyrosine receptor kinase B and Akt, as well as the postsynaptic marker PSD-95, in the ventromedial prefrontal cortex (vmPFC). Meanwhile, adolescent-typical dendritic spine pruning on excitatory pyramidal neurons in the vmPFC was expedited. Further, vmPFC-specific shRNA-mediated reduction of ROCK2, the dominant ROCK isoform in the brain, had antidepressant-like consequences. We cautiously suggest that ROCK inhibitors may have therapeutic potential for adolescent-onset depression." @default.
- W2906615611 created "2019-01-01" @default.
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- W2906615611 date "2019-04-01" @default.
- W2906615611 modified "2023-10-13" @default.
- W2906615611 title "Rho-kinase inhibition has antidepressant-like efficacy and expedites dendritic spine pruning in adolescent mice" @default.
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- W2906615611 doi "https://doi.org/10.1016/j.nbd.2018.12.015" @default.
- W2906615611 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6365018" @default.
- W2906615611 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30593834" @default.
- W2906615611 hasPublicationYear "2019" @default.
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