Open AccessPoststroke dendritic arbor regrowth requires the actin nucleator Cobl
Author(s) -
Youngmi Ji,
David Koch,
Jule González Delgado,
Madlen Günther,
Otto W. Witte,
Michael M. Kessels,
Christiane Frahm,
Britta Qualmann
Publication year - 2021
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3001399
Subject(s) - excitotoxicity , biology , stroke (engine) , dendritic spine , proteolysis , calpain , neuroscience , cortex (anatomy) , neuroprotection , microbiology and biotechnology , actin , apoptosis , programmed cell death , genetics , biochemistry , enzyme , mechanical engineering , hippocampal formation , engineering
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.