Pre-exposure to subtoxic levels prevents kainic acid lesions in organotypic hippocampal slice cultures: effects of kainic acid on parvalbumin-immunoreactive neurons and expression of heat shock protein 72 following the induction of tolerance.
The effects of kainic acid on the survival of principal neurons and parvalbumin-immunoreactive (PARV-IR) neurons, and on the expression of heat shock protein 72 immunoreactivity (HSP72-IR) were investigated in organotypic hippocampal slice cultures. Untreated cultures displayed an organotypic organization and the development and morphology of PARV-IR neurons in the hippocampus paralleled that reported to occur in vivo, with the exception of the hilar region of the dentate gyrus which exhibited a marked lack of PARV-IR neurons. No constitutive expression of HSP72 was found in untreated cultures. The lesion of CA3 neurons and the reduction in numbers of PARV-IR neurons in both CA3 and CA1 after chronic exposure to 5 microM kainic acid were similar to those reported to occur in vivo. Exposure to 1 microM doses of kainic acid resulted in a widespread appearance of HSP72-IR and the induction of tolerance to a previously toxic dose of kainic acid. These results suggest the presence of endogenous neuroprotective mechanisms, activated by a stress response which induces HSP72, and is reminiscent of the induced tolerance reported to occur after a mild ischaemic insult.
Best
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Department of Human Morphology, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.
Sundstrom
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LE
Mitchell
J
J
Wheal
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HV
D000818:Animals; D004361:Drug Tolerance; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000096:biosynthesis; D009474:Neurons / Q000737:chemistry*; D009924:Organ Culture Techniques; D010320:Parvalbumins / Q000032:analysis*; D010640:Phenothiazines; D011419:Propidium; D051381:Rats; D012016:Reference Values
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D010640:Phenothiazines; D011419:Propidium; D007608:Kainic Acid; C009469:thionine