Effect of Entorhinal Cortex on Hippocampal Neurotransmitter Function

内嗅皮层是将新皮层感觉输入汇聚到海马结构的主要供应者。在阿尔茨海默病中，内嗅皮层是最早出现神经病理改变的解剖区域。由于内嗅皮层的结构被与阿尔茨海默病相关的早期退行性过程改变，因此该区域可能涉及随着疾病恶化的记忆过程的各个方面。为探讨内嗅皮层损伤对海马生化的影响，采用在体微透析技术，观察了内嗅皮层损伤大鼠在正性重复操作学习行为过程中海马胆碱能系统和隔区多巴胺能系统的变化。提示内嗅皮层损伤可引起海马胆碱能系统的损害，但对隔区多巴胺能系统无影响，内嗅皮层-海马传递通路中断。此外，我们研究了12周的变化，在组织化学证明分布的乙酰胆碱酯酶和突触体蛋白的免疫反应性模式在海马内嗅皮质病变大鼠。本研究揭示了损失的乙酰胆碱酯酶阳性纤维和突触体素免疫反应突触前末梢在内嗅皮层病变后，在海马，突触体素免疫反应突触前末梢的减少与时间的进展。这些结果表明，内嗅皮层损伤不仅导致胆碱能功能障碍，而且海马突触的损失。这些发现为内嗅皮层的神经病理改变可能与阿尔茨海默病的记忆缺陷有关的观点提供了支持。内嗅皮层损伤的大鼠可作为研究阿尔茨海默病病理生理机制和开发治疗策略的动物模型。

The entorhinal cortex is a primary supplier of converging neocortical sensory input into the hippocampal formation. In Alzheimer's disease, the entorhinal cortex is the earliest anatomical region to show neuropathological change. Because the structure of the entorhinal cortex is altered by the early degenerative processed associated with Alzheimer's disease, this area might be involved in aspects of memory processes that deteriorate with the disease. To explore for biochemical changes of the hippocampus associated with entorhinal cortex damage, we investigated changes in hippocampal cholinergic system and septal dopaminergic system of entorhinal cortex-lesioned rat during positive reinforcemrnt operant learning behavior using an in vivo microdialysis technique. This result suggested that entorhinal cortex lesion may cause damage to the hippocampal cholinergic system having no effect on the septal dopaminergic system with disruption of the entorhinal cortex-hippocampus relay passage. Moreover, we examined 12-week changes in histochemically demonstrated distribution of acetylcholinesterase and patterns of immunoreactivity for synaptophysin in the hippocampus following an entorhinal cortex lesion in rats. The present study revealed a loss of acetylcholinesterase-positive fibers and synaptophysin-immunoreactive presynaptic terminals in the hippocampus after an entorhinal cortex lesion, and the decrease of synaptophysin-immunoreactive presynaptic terminals progressed with time. These results demonstrated that entorhinal cortex lesion causes not only cholinergic dysfunction but also synaptic loss in the hippocampus. These findings offer support for the idea that the neuropathological change of the entorhinal cortex may be associated with momory deficit in Alzheimer's disease. Rats with entorhinal cortex lesion may be useful for constructing an animal model to study the pathophysiology of Alzheimer's disease and develop new strategies for its treatment.