Badiali de Giorgi L, Bonvicini F, Bianchi D, Bossoni G, Laschi R
Drugs Exp Clin Res. 1987;13(3):185-9.
The ageing rat hippocampus undergoes ultrastructural changes, including the loss of axosomatic synapses of the granule cells. These synapses are supposed to take part in a feed-back regulation of granule cell activity, as they are inhibitory terminals of interneurons which receive afferences from the granules themselves via the giant synapses formed by the collaterals of the mossy fibres. In the present study the authors performed a quantitative analysis of axosomatic and giant synapses at the ultrastructural level in aged rats as compared with young animals. In aged rats a decrease both in axosomatic synapses and in giant synapsis vesicles was found, giving further support to the postulated feed-back mechanism. Both young and old rats were treated with L-acetyl-carnitine, a drug which favours the synthesis of acetylcholine, the main neurotransmitter deficient in old age. In aged rats the drug restored a normal number of both axosomatic synapses and giant bouton vesicles. The authors hypothesize that the drug, by a cholinergic-type mechanism, restores the excitatory afferences to the granule whose axon would thus form normal giant boutons with the interneuron, reestablishing the feed-back regulation. In young rats the drug induced a decrease only of the axosomatic synapses, suggesting that an "over-excitation" might impair the information to the local-circuit neurons, thus interrupting feed-back control.
衰老大鼠的海马体发生超微结构变化，包括颗粒细胞轴体突触的丧失。这些突触被认为参与颗粒细胞活动的反馈调节，因为它们是中间神经元的抑制性终末，这些中间神经元通过苔藓纤维侧支形成的巨大突触接收来自颗粒细胞自身的传入信号。在本研究中，作者对老年大鼠与年轻动物在超微结构水平上的轴体突触和巨大突触进行了定量分析。在老年大鼠中，发现轴体突触和巨大突触小泡均减少，这进一步支持了假定的反馈机制。年轻和老年大鼠均用L-乙酰肉碱进行治疗，L-乙酰肉碱是一种有利于乙酰胆碱合成的药物，乙酰胆碱是老年时缺乏的主要神经递质。在老年大鼠中，该药物使轴体突触和巨大终扣小泡的数量恢复正常。作者推测，该药物通过胆碱能型机制恢复对颗粒细胞的兴奋性传入信号，其轴突因此会与中间神经元形成正常的巨大终扣，从而重新建立反馈调节。在年轻大鼠中，该药物仅导致轴体突触减少，这表明“过度兴奋”可能会损害向局部回路神经元传递的信息，从而中断反馈控制。
