Richter-Levin G, Segal M
Department of Neurobiology, Weizmann Institute, Rehovot, Israel.
Ann N Y Acad Sci. 1993 Sep 24;695:254-7. doi: 10.1111/j.1749-6632.1993.tb23063.x.
The cholinergic hypothesis of senile dementia proposes that an age-dependent reduction of central cholinergic functions accounts for the severe cognitive deficits seen in aged rats. A careful examination of the experimental evidence cited in support of this hypothesis reveals that it cannot account for some behavioral observations. We have modified this hypothesis and wish to propose that serotonin and acetylcholine interact to allow normal cognitive functions in the brain. Thus, a partial reduction in both cholinergic and serotonergic functions will cause severe memory impairment in young as well as in aged rats. We found that restoration of the serotonergic innervation in the hippocampus of serotonin depleted rats, using tissue transplants, can restore impaired behavior. We have localized a memory-related interaction between serotonin and acetylcholine in the hippocampus and are in the process of identifying a physiological function which may underly this interaction.
老年痴呆症的胆碱能假说提出，中枢胆碱能功能随年龄增长而下降是老年大鼠出现严重认知缺陷的原因。仔细审视为支持这一假说而引用的实验证据后发现，它无法解释某些行为观察结果。我们对这一假说进行了修正，并提出5-羟色胺和乙酰胆碱相互作用以使大脑具备正常认知功能。因此，胆碱能和5-羟色胺能功能的部分减退会导致幼年和老年大鼠出现严重的记忆损伤。我们发现，通过组织移植恢复5-羟色胺耗竭大鼠海马体中的5-羟色胺能神经支配，可以恢复受损行为。我们已确定海马体中5-羟色胺与乙酰胆碱之间存在与记忆相关的相互作用，并且正在确定可能是这种相互作用基础的生理功能。
