Regional Neurodegeneration in vitro : The Protective Role of Neural Activity.

Autor: Mott RE; Cell Press, Cambridge, MA, United States., von Reyn CR; School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, United States.; Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, United States., Firestein BL; Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, United States., Meaney DF; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States.; Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States.
Jazyk: angličtina
Zdroj: Frontiers in computational neuroscience [Front Comput Neurosci] 2021 Mar 29; Vol. 15, pp. 580107. Date of Electronic Publication: 2021 Mar 29 (Print Publication: 2021).
DOI: 10.3389/fncom.2021.580107
Abstrakt: Traumatic brain injury is a devastating public health problem, the eighth leading cause of death across the world. To improve our understanding of how injury at the cellular scale affects neural circuit function, we developed a protocol to precisely injure individual neurons within an in vitro neural network. We used high speed calcium imaging to estimate alterations in neural activity and connectivity that occur followed targeted microtrauma. Our studies show that mechanically injured neurons inactivate following microtrauma and eventually re-integrate into the network. Single neuron re-integration is dependent on its activity prior to injury and initial connections in the network: more active and integrated neurons are more resistant to microtrauma and more likely to re-integrate into the network. Micromechanical injury leads to neuronal death 6 h post-injury in a subset of both injured and uninjured neurons. Interestingly, neural activity and network participation after injury were associated with survival in linear discriminate analysis (77.3% correct prediction, Wilks' Lambda = 0.838). Based on this observation, we modulated neuronal activity to rescue neurons after microtrauma. Inhibition of neuronal activity provided much greater survivability than did activation of neurons (ANOVA, p < 0.01 with post-hoc Tukey HSD, p < 0.01). Rescue of neurons by blocking activity in the post-acute period is partially mediated by mitochondrial energetics, as we observed silencing neurons after micromechanical injury led to a significant reduction in mitochondrial calcium accumulation. Overall, the present study provides deeper insight into the propagation of injury within networks, demonstrating that together the initial activity, network structure, and post-injury activity levels contribute to the progressive changes in a neural circuit after mechanical trauma.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Mott, von Reyn, Firestein and Meaney.)
Databáze: MEDLINE