Roberson M R, Kolasa K, Parsons D S, Harrell L E
Alzheimer's Disease Center, Department of Psychology, Veterans Administration Medical Center and University of Alabama at Birmingham, 35294, USA.
Neuroscience. 1997 Sep;80(2):413-8. doi: 10.1016/s0306-4522(97)00153-x.
Our laboratory has been utilizing the model of hippocampal sympathetic ingrowth, which has been suggested to occur in Alzheimer's disease, to investigate the effects of cholinergic denervation and hippocampal rearrangements. After cholinergic denervation by medial septal lesions, peripheral sympathetic fibres originating from the superior cervical ganglia grow into the rat hippocampus. This hippocampal sympathetic ingrowth can be prevented by superior cervical ganglionectomy. We examined the long-term effects of these treatments on muscarinic receptors by comparing [3H]quinuclidinyl benzilate binding in rat dorsal hippocampus four and 12 weeks post lesion. Four groups of animals were employed, including controls (sham lesion+sham ganglionectomy), animals with ingrowth (medial septal lesion+ sham ganglionectomy), animals with cholinergic denervation alone (medial septal lesion+ ganglionectomy), and ganglionectomy alone (sham lesion+ganglionectomy) animals. In dorsal hippocampus four weeks post lesion, binding affinity was similar among all groups, while muscarinic receptor number was increased in ingrowth animals as compared to both the control (P<0.0002) and ganglionectomy animals (P<0.01). By 12 weeks, receptor affinity was significantly decreased in ingrowth (P<0.0001) and cholinergic denervation (P<0.0003) groups, and receptor number remained significantly elevated in ingrowth animals as compared to control (P<0.01), ganglionectomy (P<0.02) and cholinergic denervation (P<0.01) groups. The decrease in muscarinic receptor affinity may provide some insight into the ineffectiveness of cholinomimetic therapies in Alzheimer's disease, in that agonist efficacy would be reduced at the receptor.
我们实验室一直采用海马体交感神经长入模型（该模型被认为会在阿尔茨海默病中出现）来研究胆碱能去神经支配和海马体重排的影响。在内侧隔区损伤导致胆碱能去神经支配后，源自颈上神经节的外周交感神经纤维长入大鼠海马体。这种海马体交感神经长入可通过颈上神经节切除术来预防。我们通过比较损伤后4周和12周大鼠背侧海马体中[3H]喹核醇基苯甲酸酯的结合情况，研究了这些处理对毒蕈碱受体的长期影响。使用了四组动物，包括对照组（假损伤+假神经节切除术）、有神经长入的动物（内侧隔区损伤+假神经节切除术）、仅接受胆碱能去神经支配的动物（内侧隔区损伤+神经节切除术）以及仅接受神经节切除术的动物（假损伤+神经节切除术）。损伤后4周，所有组之间的结合亲和力相似，而与对照组（P<0.0002）和神经节切除术组动物（P<0.01）相比，有神经长入的动物中毒蕈碱受体数量增加。到12周时，有神经长入组（P<0.0001）和胆碱能去神经支配组（P<0.0003）的受体亲和力显著降低，与对照组（P<0.01）、神经节切除术组（P<0.02）和胆碱能去神经支配组（P<0.01）相比，有神经长入的动物中受体数量仍显著升高。毒蕈碱受体亲和力的降低可能为理解拟胆碱疗法在阿尔茨海默病中无效提供一些线索，因为在受体处激动剂的效力会降低。
