Cyclin D1 in excitatory neurons of the adult brain enhances kainate-induced neurotoxicity.
G1-phase cyclin D1 (cD1) expression has been documented in post-mitotic neurons undergoing apoptosis, leading others to propose that attempted cell cycle re-entry may induce cell death. Here, cD1 immunoreactivity was found in a subpopulation of healthy excitatory neurons throughout the brain. Most striking was the selective cD1 expression in hippocampal pyramidal neurons, an especially vulnerable cell group. Seizure threshold, cD1 induction and CA1 neuron death were examined following application of kainate (KA) or pentylenetetrazole (PTZ) in cD1 heterozygous (+/-) and wildtype mice to determine whether baseline cD1 correlates with pathology. cD1+/- mice displayed resistance to KA, but not PTZ-induced seizures and had reduced or equivalent cytotoxicity respectively, compared with wildtype. KA administration, but not PTZ, induced cD1 expression. These findings suggest that basal cD1 expression may render hippocampal circuits more susceptible to particular epileptogenic agents and excitotoxic cell death, though cD1 is not a direct precipitant in apoptosis.
Koeller
Hajira B
HB
Graduate Program in Neuroscience, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 1300 York Avenue, Box 239, New York, NY 10065, USA.
Ross
M Elizabeth
ME
Glickstein
Sara B
SB
D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D003292:Convulsants / Q000494:pharmacology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009498:Neurotoxins / Q000633:toxicity; D010433:Pentylenetetrazole / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003292:Convulsants; D009498:Neurotoxins; D019938:Cyclin D1; D007608:Kainic Acid; D010433:Pentylenetetrazole