Enhanced autophagy signaling in diabetic rats with ischemia-induced seizures

Brain Res. 2016 Jul 15:1643:18-26. doi: 10.1016/j.brainres.2016.04.054. Epub 2016 Apr 25.

Abstract

Seizures are among the most common neurological sequelae of stroke, and ischemic insult in diabetes notably increases the incidence of seizures. Recent studies indicated that autophagy influences the outcome of stroke and involved in epileptogenesis. However, the association of autophagy and post-ischemic seizures in diabetes remains unclear. The present study aimed to reveal the involvement of autophagy in the seizures following cerebral ischemia in diabetes. Diabetes was induced in adult male Wistar rats by intraperitoneal injection of streptozotocin (STZ). The diabetic rats were subjected to transient forebrain ischemia. The neuronal damage was assessed using hematoxylin-eosin staining. Western blotting and immunohistochemistry were performed to investigate the alteration of autophagy marker microtubule-associated protein light chain 1B (LC3B). The results showed that all diabetic animals developed seizures after ischemia. However, no apparent cell death was observed in the hippocampus of seizure rats 12h after the insult. The expression of LC3B was significantly enhanced in naïve animals after ischemia and was further increased in diabetic animals after ischemia. Immunofluorescence double-labeling study indicated that LC3B was mainly increased in neurons. Our study demonstrated, for the first time, that autophagy activity is significantly increased in diabetic animals with ischemia-induced seizures. Further studies are needed to explore the role of autophagy in seizure generation after ischemia in diabetic conditions.

Keywords: Epilepsy; Hippocampus; Hyperglycemia; LC3; Stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Brain Ischemia / complications
  • Brain Ischemia / metabolism*
  • Diabetes Complications / metabolism*
  • Disease Models, Animal
  • Hippocampus / pathology
  • Hippocampus / physiology
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Neurons / physiology
  • Rats
  • Rats, Wistar
  • Seizures / etiology
  • Seizures / metabolism*
  • Signal Transduction

Substances

  • LC3 protein, rat
  • Microtubule-Associated Proteins