Regionally selective neurotoxicity of NMDA and colchicine is independent of hippocampal neural circuitry.
The mechanisms by which cerebral ischemia and several neurotoxins cause regionally selective damages to the hippocampal formation are largely unknown. The CA1-selective toxicity of N-methyl--aspartate (NMDA), the CA3-selective toxicity of kainate, and the dentate gyrus (DG)-selective toxicity of colchicine were observed in organotypic entorhino-hippocampal cultures. The selective neurotoxicity of NMDA and colchicine but not kainate was present in isolated tissue cultures of each hippocampal subregion, suggesting that the regional vulnerability is irrespective of the hippocampal trisynaptic pathway. Dispersed cultures of neurons prepared from Ammon's horn and the DG still exhibited a preference for susceptibility to NMDA and colchicine, respectively. Thus, the neurons per se appear to be inherently susceptible to specific toxins independently of their original loci, intrinsic neural circuits, vascular system, or other systemic factors.
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ikegaya@tk.airnet.ne.jp
Y
Y
Ikegaya
N
N
Matsuki
D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects; D018728:Entorhinal Cortex / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology*; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar
D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D016202:N-Methylaspartate; D003078:Colchicine