Cyclin D1 in excitatory neurons of the adult brain enhances kainate-induced neurotoxicity

NEUROBIOLOGY OF DISEASE

卷:31

Article

Koeller, Hajira B.^1,2  Ross, M. Elizabeth^1,2  Glickstein, Sara B.¹ 

[1] Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10065 USA

[2] Cornell Univ, Weill Med Coll, Grad Program Neurosci, New York, NY 10065 USA

关键词: cyclin D1;    kainate;    pentylenetetrazole;    CA1;    excitotoxicity;    seizure;    hippocampus;    cell cycle;    apoptosis;    excitatory neurons;   

DOI  :  10.1016/j.nbd.2008.04.010

来源: Elsevier

【 摘 要 】

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. (C) 2008 Elsevier Inc. All rights reserved.

【 授权许可】

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