Active shrinkage protects neurons following axonal transection


Aydın M. Ş., Bay S., Yiğit E. N., ÖZGÜL C., Kaval Oğuz E., Konuk E. Y., ...More

ISCIENCE, vol.26, no.10, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 26 Issue: 10
  • Publication Date: 2023
  • Doi Number: 10.1016/j.isci.2023.107715
  • Journal Name: ISCIENCE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Directory of Open Access Journals
  • Keywords: Biological sciences, Neuroscience, Physiology
  • Istanbul Medipol University Affiliated: Yes

Abstract

Trauma, vascular events, or neurodegenerative processes can lead to axonal injury and eventual transection (axotomy). Neurons can survive axotomy, yet the underlying mechanisms are not fully understood. Excessive water entry into injured neurons poses a particular risk due to swelling and subsequent death. Using in vitro and in vivo neurotrauma model systems based on laser transection and surgical nerve cut, we demonstrated that axotomy triggers actomyosin contraction coupled with calpain activity. As a consequence, neurons shrink acutely to force water out through aquaporin channels preventing swelling and bursting. Inhibiting shrinkage increased the probability of neuronal cell death by about 3-fold. These studies reveal a previously unrecognized cytoprotective response mechanism to neurotrauma and offer a fresh perspective on pathophysiological processes in the nervous system.