Active shrinkage protects neurons following axonal transection

Mehmet Şerif Aydın; Sadık Bay; Esra Nur Yiğit; Cemil Özgül; Elif Kaval Oğuz; Elçin Yenidünya Konuk; Neşe Ayşit; Nureddin Cengiz; Ender Erdoğan; Aydın Him; Mehmet Koçak; Emrah Eroglu; Gürkan Öztürk

doi:10.1016/j.isci.2023.107715

Active shrinkage protects neurons following axonal transection

iScience. 2023 Aug 25;26(10):107715. doi: 10.1016/j.isci.2023.107715. eCollection 2023 Oct 20.

Authors

Mehmet Şerif Aydın¹, Sadık Bay¹, Esra Nur Yiğit¹, Cemil Özgül¹, Elif Kaval Oğuz², Elçin Yenidünya Konuk³, Neşe Ayşit^{1

4}, Nureddin Cengiz⁵, Ender Erdoğan⁶, Aydın Him⁷, Mehmet Koçak^{8

9}, Emrah Eroglu¹, Gürkan Öztürk^{1

10}

Affiliations

¹ Regenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul 34810, Türkiye.
² Department of Science Education, Faculty of Education, Yüzüncü Yıl University, Van 65080, Türkiye.
³ Department of Medical Biology, School of Medicine, Bakırçay University, İzmir 35665, Türkiye.
⁴ Department of Medical Biology and Genetics, School of Medicine, Istanbul Medipol University, Istanbul 34810, Türkiye.
⁵ Department of Histology and Embryology, School of Medicine, Bandırma Onyedi Eylül University, Bandırma, Balıkesir 10200, Türkiye.
⁶ Department of Histology and Embryology, School of Medicine, Selçuk University, Konya 42130, Türkiye.
⁷ Department of Physiology, School of Medicine, Bolu Abant İzzet Baysal University, Bolu 14030, Türkiye.
⁸ Biostatistics and Bioinformatics Analysis Unit, Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul 34810, Türkiye.
⁹ Department of Biostatistics and Medical Informatics, International School of Medicine, Istanbul Medipol University, Istanbul 34810, Türkiye.
¹⁰ Department of Physiology, International School of Medicine, Istanbul Medipol University, Istanbul 34810, Türkiye.

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.

Keywords: Biological sciences; Neuroscience; Physiology.