RhoA-ROCK Inhibition Reverses Synaptic Remodeling and Motor and Cognitive Deficits Caused by Traumatic Brain Injury

Overview

Journal Sci Rep

Specialty Science

Date 2017 Sep 8

PMID 28878396

Citations 25

Authors

Shalaka Mulherkar

Karen Firozi

Wei Huang

Mohammad Danish Uddin

Raymond J Grill

Mauro Costa-Mattioli

Claudia Robertson

Kimberley F Tolias

Affiliations

Soon will be listed here.

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.

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