Mitochondrial therapy promotes regeneration of injured hippocampal neurons

Biochim Biophys Acta Mol Basis Dis. 2018 Sep;1864(9 Pt B):3001-3012. doi: 10.1016/j.bbadis.2018.06.012. Epub 2018 Jun 15.

Abstract

Due to the inhibitory microenvironment and reduced intrinsic growth capacity of neurons, neuronal regeneration of central nervous system remains challenging. Neurons are highly energy demanding and require sufficient mitochondria to support cellular activities. In response to stimuli, mitochondria undergo fusion/fission cycles to adapt to environment. It is thus logical to hypothesize that the plasticity of mitochondrial dynamics is required for neuronal regeneration. In this study, we examined the role of mitochondrial dynamics during regeneration of rat hippocampal neurons. Quantitative analysis showed that injury induced mitochondrial fission. As mitochondrial dysfunction has been implicated in neurodegenerative diseases, we tested the possibility that the mitochondrial therapy may promote neuronal regeneration. Supplying freshly isolated mitochondria to the injured hippocampal neurons not only significantly increased neurite re-growth but also restored membrane potential of injured hippocampal neurons. Together, our findings support the importance of mitochondrial dynamics during regeneration of injured hippocampal neurons and highlight the therapeutic prospect of mitochondria to the injured central nervous system.

Keywords: Brain injury; Mitochondrial morphogenesis; Neuronal regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries, Traumatic / complications
  • Brain Injuries, Traumatic / pathology
  • Brain Injuries, Traumatic / therapy*
  • Cell- and Tissue-Based Therapy / methods*
  • Cells, Cultured
  • Disease Models, Animal
  • Hippocampus / cytology
  • Hippocampus / injuries
  • Hippocampus / physiology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / metabolism
  • Mitochondria / transplantation*
  • Mitochondrial Dynamics / physiology
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / therapy
  • Neurons / physiology*
  • Primary Cell Culture
  • Rats
  • Rats, Sprague-Dawley
  • Regeneration*