RhoA-ROCK Inhibition Reverses Synaptic Remodeling and Motor and Cognitive Deficits Caused by Traumatic Brain Injury
Year: 2017
Type: article
Abstract: Traumatic brain injury (TBI) causes extensive neural damage, often resulting in long-term cognitive impairments. Unfortunately, effective treatments for TBI remain elusive. The RhoA-ROCK signaling pathway is a potential therapeutic target since it is activated by TBI and can promote the retraction of dendritic spines/synapses, which are critical for information processing and memory storage. To test this hypothesis, RhoA-ROCK signaling was blocked by RhoA deletion from postnatal neurons or treatment with the ROCK inhibitor fasudil. We found that TBI impairs both motor and cognitive performance and inhibiting RhoA-ROCK signaling alleviates these deficits. Moreover, RhoA-ROCK inhibition prevents TBI-induced spine remodeling and mature spine loss. These data argue that TBI elicits pathological spine remodeling that contributes to behavioral deficits by altering synaptic connections, and RhoA-ROCK inhibition enhances functional recovery by blocking this detrimental effect. As fasudil has been safely used in humans, our results suggest that it could be repurposed to treat TBI.
Source: Scientific Reports
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: Adhesion-GPCRs: Regulators of dendritic development, synaptogenesis and mental health, G3015215220, Baylor Intellectual and Developmental Disabilities Research Centers, Baylor Intellectual and Developmental Disabilities Research Center, G6143698708, G7050813997, MISSION CONNECT MILD TBI TRANSLATIONAL RESEARCH CONSORTIUM, G8192083305, Tecan EVO GenePaint robot, G9000066955, Signaling Mechanisms Regulating Rho GTPase-Dependent Synaptic Plasticity Underlying Memory in Health and Disease, G942658896
OpenAlex ID: W2752641978