Striatal neurones show sustained recovery from severe hypoglycaemic insult.
Glucose deprivation provides a reliable model to investigate cellular responses to metabolic dysfunction, and is reportedly associated with permanent cell death in many paradigms. Consistent with previous studies, primary cultures of rat striatal neurones exposed to 24-h hypoglycaemia showed dramatically decreased sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) metabolism (used as a marker of cell viability) and increased TUNEL staining, suggesting widespread DNA damage typical of apoptotic cell death. Remarkably, restoration of normal glucose levels initiated a sustained recovery in XTT staining, along with a concomitant decrease in TUNEL staining, even after 24 h of hypoglycaemia, suggesting recovery of damaged neurones and repair of nicked DNA. No alterations in the levels of four DNA repair proteins could be detected during hypoglycaemia or recovery. A reduction in intracellular calcium concentration was seen in recovered cells. These data suggest that striatal cells do not die after extended periods of glucose deprivation, but survive in a form of suspended animation, with sufficient energy to maintain membrane potential.
McDermott
C J
CJ
Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK.
Bradley
K N
KN
McCarron
J G
JG
Palmer
A M
AM
Morris
B J
BJ
D000818:Animals; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D007003:Hypoglycemia / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors; D051028:bcl-2-Associated X Protein
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013778:Tetrazolium Salts; D051028:bcl-2-Associated X Protein; D020169:Caspases; D005947:Glucose