Uchida S, Suzuki A, Kagitani F, Hotta H
Department of the Autonomic Nervous System, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, 173-0015, Tokyo, Japan.
Neurosci Lett. 2000 Nov 17;294(2):109-12. doi: 10.1016/s0304-3940(00)01556-1.
The present study examined the age-related changes in the cholinergic vasodilative system originating in the nucleus basalis of Meynert (NBM) and projecting to the cerebral cortex using Wistar rats of three different ages; young adult (4-7 months), old (24-25 months), and very old (32-42 months) rats. The vasodilative responses in frontal and parietal cortices, measured by laser Doppler flowmetry, induced by electrical stimulation of NBM without blood pressure response were well maintained in old rats, but declined significantly in very old rats. Extracellular acethylcholine (ACh) release in both cortices collected by a microdialysis technique showed both basal levels and response to NBM stimulation to be well maintained in both old and very old rats. The vasodilative cerebral blood flow response elicited by stimulation of the muscarinic ACh receptors, using their agonist, arecoline, was also well maintained in old and very old rats. Considering the present data and our previous finding that the cerebral cortical vasodilative response to activation of the nicotinic ACh receptors using their agonist, nicotine, was markedly reduced in very old rats (Neurosci. Lett., 228 (1997) 203), it was concluded that the age-related decline of nicotinic ACh receptor activity was a cause of the decline of the vasodilative responses elicited by NBM stimulation in very old rats. This result suggests that a reduction of the cholinergic vasodilative system in very old rats due to decreased activity of the nicotinic ACh receptor may cause insufficient blood flow in the cortex when the cortical neurons require.
本研究使用三种不同年龄的Wistar大鼠，即年轻成年大鼠（4 - 7个月）、老年大鼠（24 - 25个月）和高龄大鼠（32 - 42个月），研究了起源于Meynert基底核（NBM）并投射至大脑皮层的胆碱能血管舒张系统的年龄相关变化。通过激光多普勒血流仪测量，在无血压反应的情况下，电刺激NBM所诱导的额叶和顶叶皮层的血管舒张反应在老年大鼠中保持良好，但在高龄大鼠中显著下降。采用微透析技术收集的两个皮层中的细胞外乙酰胆碱（ACh）释放显示，老年和高龄大鼠的基础水平以及对NBM刺激的反应均保持良好。使用毒蕈碱型ACh受体激动剂槟榔碱刺激所引发的脑血管舒张血流反应在老年和高龄大鼠中也保持良好。结合本研究数据以及我们之前的发现，即使用烟碱型ACh受体激动剂尼古丁激活时，高龄大鼠大脑皮层的血管舒张反应显著降低（《神经科学快报》，228 (1997) 203），得出结论：烟碱型ACh受体活性的年龄相关下降是高龄大鼠中NBM刺激所引发的血管舒张反应下降的原因。该结果表明，由于烟碱型ACh受体活性降低，高龄大鼠胆碱能血管舒张系统的减少可能在皮层神经元需要时导致皮层血流不足。
