dibutyryl-cAMPの選択的細胞体障害作用

NEUROEXCITOTOXIC ACTION OF DB-CAMP : LESIONING OF NEURONAL CELL BODIES WHILE SPARING FIBERS OF PASSAGE

　dibutyryl-cyclic adenosine 3’5’—mono-phosphate（db-cAMP）を無麻酔下または麻酔下のラット扁桃核に注入して，AChE陽性線維に対する影響を検討し，kainateと比較した。その結果は次の様であった。（1）無麻酔下では，db-cAMP，kainateにより，典型的なAM発作あるいは二次性全汎化けいれんが誘発された。いずれの注入でも次のような共通の組織所見が見られた。即ち，注入側AMでは神経細胞の脱落がもたらされたが，AChE陽性線維の脱落はなかった。注人側海馬では発作強度に対応して錐体細胞の脱落が見られた。注入側piriform cortexでは神経細胞の脱落はなかったが，AChE陽性線維が脱落していた。（2）麻酔下でも注人側AMとpiriform cortexに無麻酔下と同様の所見が得られた。以上のことから，db-cAMPはkainateと類似したneuroexcitotoxinであることが示唆される。

In our previous study, we have demonstrated that intra-amygdaloid injection of dibutyryl-cAMP causes neuronal damage in the injected AM and the CA 1-3 subfields of the ipsilateral hippocam-pus in addition to epileptic seizures. This result suggested that db-cAMP is a new neuroexci-totoxin. In this study, we examined compara-tive morphological effect on acetylcholinesterase (AChE) following intra-amygdaloid injection of db-cAMP or, kainate. In Expt. 1, twenty rats received 100 μg db-cAMP (N=10), 0.5 μg kainate (N= 4), or saline as a vehicle (N=6), through the implanted cannula under non-anesthesia. Ei-ther kainate or db-cAMP produced epileptic seizures, while saline induced no electroclinical ictal response. Following db-cAMP or kainate injection, neuronal loss was observed in the in-jected AM, but AChE positive fibers were intact. In the hippocampus ipsilateral to the injected AM, the loss of pyramidal cells was also noted in accordance with the severity of seizure intensity. In the piriform cortex ipsilateral to the injected AM, the loss of AChE-positive fibers were seen, but sparing neuronal cell bodies. In Expt. 2, ninete-en rats were injected with 100 μg db-cAMP (N= 7), 0.5 μg kainate (N= 7), or saline as a vehicle (N= 5) under pentobarbital anesthesia. Kainate or db-cAMP produced few sporadic spikes. In the injected AM and the piriform cortex ipsilateral to the injection site, db-cAMP or kainate induced the same morphological changes as seen in Expt, 1. These results strongly suggest that db-cAMP is a new neuroexcitotoxin characterized by a un-ique morphological effects, i. e. selectively destruc-tion of neuronal cell bodies while sparing fibers of passage.