Calbindin D28K gene transfer via herpes simplex virus amplicon vector decreases hippocampal damage in vivo following neurotoxic insults.
Increases in cytoplasmic Ca2+ concentration ([Ca2+]i) can lead to neuron death. Preventing a rise in [Ca2+]i by removing Ca2+ from the extracellular space or by adding Ca2+ chelators to the cytosol of target cells ameliorates the neurotoxicity associated with [Ca2+]i increases. Another potential route of decreasing the neurotoxic impact of Ca2+ 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 D28K, 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 D28K 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 D28K vector in an intact brain may prove to be beneficial during changes in Ca2+ homeostasis caused by neurological trauma associated with aging and certain neurological diseases.
Phillips
R G
RG
Department of Biological Sciences, Stanford University, California 94305-5020, USA.
Meier
T J
TJ
Giuli
L C
LC
McLaughlin
J R
JR
Ho
D Y
DY
Sapolsky
R M
RM
D000818:Animals; D000963:Antimetabolites / Q000633:toxicity*; D064092:Calbindin 1; D064026:Calbindins; D002470:Cell Survival / Q000187:drug effects; D004579:Electron Transport / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects; D011725:Pyridines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism*; D018139:Simplexvirus / Q000235:genetics; D014475:Uncoupling Agents / Q000633:toxicity
D000963:Antimetabolites; C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D018690:Excitatory Amino Acid Agonists; D009419:Nerve Tissue Proteins; D011725:Pyridines; D064030:S100 Calcium Binding Protein G; D014475:Uncoupling Agents; C010835:3-acetylpyridine; D007608:Kainic Acid