Abstract

Dynamin-like protein I (DLP-1) is an important mitochondrial fission and fusion protein that is associated with apoptotic cell death in neurodegenerative diseases. In this study, we investigated DLP-1 expression in a focal cerebral ischemia animal model and glutamate-exposed hippocampal-derived cell line. Middle cerebral artery occlusion (MCAO) was surgically induced in adult male rats to induce focal cerebral ischemic injury. Brain tissues were collected 24 hours after the onset of MCAO. MCAO induces an increase in infarct volume and histopathological changes in the cerebral cortex. We identified a decrease in DLP-1 in the cerebral cortices of MCAO-injured animals using a proteomic approach and Western blot analysis. Moreover, glutamate treatment significantly decreased DLP-1 expression in a hippocampal-derived cell line. The decrease in DLP-1 indicates mitochondrial dysfunction. Thus, these results suggest that neuronal cell injury induces a decrease in DLP-1 levels and consequently leads to neuronal cell death.

Highlights

  • Dynamin-like protein I (DLP-1) is an important mitochondrial fission and fusion protein that is associated with apoptotic cell death in neurodegenerative diseases

  • Cerebral ischemia caused by surgical induction of Middle cerebral artery occlusion (MCAO) induces neuronal cell death in cerebral cortex

  • We focused on DLP1 expression in the cerebral cortex after MCAO and as well as in glutamate-exposed hippocampal neurons

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Summary

Introduction

Dynamin-like protein I (DLP-1) is an important mitochondrial fission and fusion protein that is associated with apoptotic cell death in neurodegenerative diseases. We investigated DLP-1 expression in a focal cerebral ischemia animal model and glutamate-exposed hippocampal-derived cell line. The decrease in DLP-1 indicates mitochondrial dysfunction These results suggest that neuronal cell injury induces a decrease in DLP-1 levels and leads to neuronal cell death. Cerebral ischemic injury induces intracellular calcium overload, mitochondrial dysfunction, reactive oxygen species (ROS) generation, inflammation, and excitotoxicity [1,2]. This leads to serious neuronal cell damage, disruption of neuronal function, and adult disability.

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