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Calbindin D 28K Gene Transfer via Herpes Simplex Virus Amplicon Vector Decreases Hippocampal Damage In Vivo Following Neurotoxic Insults
Author(s) -
Phillips Russell G.,
Meier Timothy J.,
Giuli Lisa C.,
McLaughlin John R.,
Ho Dora Y.,
Spolsky Robert M.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0731200.x
Subject(s) - neurotoxicity , calbindin , hippocampal formation , herpes simplex virus , dentate gyrus , biology , calcium , in vivo , excitotoxicity , calcium binding protein , extracellular , microbiology and biotechnology , chemistry , neuroscience , biochemistry , medicine , programmed cell death , toxicity , immunology , virus , apoptosis
: Increases in cytoplasmic Ca 2+ concentration ([Ca 2+ ] i ) can lead to neuron death. Preventing a rise in [Ca 2+ ] i by removing Ca 2+ from the extracellular space or by adding Ca 2+ chelators to the cytosol of target cells ameliorates the neurotoxicity associated with [Ca 2+ ] i increases. Another potential route of decreasing the neurotoxic impact of Ca 2+ is to overexpress one of the large number of constitutive calcium‐binding proteins. Previous studies in this laboratory demonstrated that overexpression of the gene for the calcium‐binding protein calbindin D 28K , via herpes simplex virus (HSV) amplicon vector, increases the survival of hippocampal neurons in vitro following energetic or excitotoxic insults but not following application of sodium cyanide. We now report that in vivo hippocampal infection with the calbindin D 28K HSV vector increases neuronal survival in the dentate gyrus after application of the antimetabolite 3‐acetylpyridine and increases transsynaptic neuronal survival in area CA3 following kainic acid neurotoxicity. The protective effects of infection with the calbindin D 28K vector in an intact brain may prove to be beneficial during changes in Ca 2+ homeostasis caused by neurological trauma associated with aging and certain neurological diseases.