Poststroke dendritic arbor regrowth requires the actin nucleator Cobl

Abstract

Ischemic stroke is a major cause of death and long-term disability. We demonstrate that middle cerebral artery occlusion (MCAO) in mice leads to a strong decline in dendritic arborization of penumbral neurons. These defects were subsequently repaired by an ipsilateral recovery process requiring the actin nucleator Cobl. Ischemic stroke and excitotoxicity, caused by calpain-mediated proteolysis, significantly reduced Cobl levels. In an apparently unique manner among excitotoxicity-affected proteins, this Cobl decline was rapidly restored by increased mRNA expression and Cobl then played a pivotal role in poststroke dendritic arbor repair in peri-infarct areas. In Cobl knockout (KO) mice, the dendritic repair window determined to span day 2 to 4 poststroke in wild type (WT) strikingly passed without any dendritic regrowth. Instead, Cobl KO penumbral neurons of the primary motor cortex continued to show the dendritic impairments caused by stroke. Our results thereby highlight a powerful poststroke recovery process and identified causal molecular mechanisms critical during poststroke repair.

Structural plasticity of motor cortices assessed by voxel-based morphometry and immunohistochemical analysis following internal capsular infarcts in macaque monkeys

“…2008 ; Murphy and Corbett 2009 ; Wu et al. 2014 ; Ji et al. 2021 ), and compensatory dendritic changes are known to occur in the cortical regions more proximal to the lesion in less damaged individuals ( Contestabile et al.…”

Dendrite injury, but not axon injury, triggers neuroprotection in Drosophila models of neurodegenerative disease

“…65 In addition, the importance of actin nucleator Cobl in mice and the actin regulators RAC GTPase CED-10 and RhoGEF TIAM-1 in C. elegans for dendrite regeneration suggests a key role for the actin cytoskeleton in the regeneration process of dendrites. 66,67 Similarly, the MT binding protein Patronin and its microtubule nucleation function have been implicated in dendrite regeneration. [68][69][70] Our results suggest that stabilization of F-actin plays an important role in the response to dendrite injury and subsequent ( regeneration.…”