Neuroprotection of cultured foetal rat hippocampal cells against glucose deprivation: are GABAergic neurons less vulnerable or more sensitive to TCP protection?
In the rat brain, hippocampal neurons are particularly sensitive to secondary excitotoxic injury induced by ischaemia or hypoglycaemia. To determine some distinctive features of vulnerability among neuronal phenotypes in the hippocampus following a metabolic insult, we used an in vitro model of mild glucose deprivation. Primary cultures from the rat hippocampus (21 days in vitro) were deprived of glucose for 4 h and then were returned to the standard medium for 24 or 48 h. Survival of the GABAergic neuronal population was evaluated both by measuring [3H]GABA uptake and by counting GAD65-immunostained cells. This was compared with the survival of the total neuronal population evaluated by counting the neurofilament-200-immunostained cells. Glucose deprivation for 4 h followed by a recovery period of 48 h induced a decrease of 59% and 40% in the number of GAD65- and neurofilament-200-immunostained cells, respectively. Thus, GABAergic neurons were slightly more vulnerable to glucose deprivation than the other neurons in the hippocampal cell cultures. When the excitotoxic component of cellular death was blocked in the presence of TCP, an NMDA-antagonist, the survival of GABAergic neurons was almost complete after 48 h of recovery. In contrast, measurements of the release of lactate dehydrogenase in the medium indicated that TCP largely protected hippocampal cells after 24 h but was ineffective after 48 h. This observation was confirmed by immunostaining data which showed that after 48 h TCP did not significantly increase the survival of neurofilament-200-immunostained cells. These results indicate that after glucose deprivation and a recovery period of 48 h, GABAergic neurons in hippocampal cell cultures are not more resistant than other neurons but they are more sensitive to TCP protection.
Chaudieu
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Unité INSERM 336, ENSCM, 8 rue de lEcole Normale, 34296 Montpellier Cedex 5, France. Chaudieu@cit.enscm.fr
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D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004351:Drug Resistance; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency*; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats / Q000196:embryology; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C012058:tenocyclidine; D007770:L-Lactate Dehydrogenase; D005947:Glucose; D010622:Phencyclidine