Abdulla F A, Abu-Bakra M A, Calaminici M R, Stephenson J D, Sinden J D
Department of Psychology, Institute of Psychiatry, London, UK.
Neurobiol Aging. 1995 Jan-Feb;16(1):41-52. doi: 10.1016/0197-4580(95)80006-d.
The present study investigated the performance of rats at 3-4 months and 21 months of age in the Morris water maze and correlated age-related cognitive deficits with changes in both cholinergic and GABAergic systems in the frontal cortex. The older rats were divided into two groups, unimpaired old and impaired old according to their ability to find a hidden submerged platform in the water maze, for electrophysiological, neurochemical, and morphological studies. The firing rate of frontal cortical neurones was recorded from the motor area of the frontal cortex under urethane anaesthesia and was found to be significantly slower in the two aged groups of rats compared to the young rats, but there were no differences between the two aged groups. The sensitivity of frontal cortex neurones of the impaired and unimpaired old age groups to ACh and to carbachol was significantly lower than that of the young group, but there were no differences between the two old age groups. In contrast, sensitivity of frontal cortex neurones to bicuculline was significantly higher in the aged rats compared with the young rats and was significantly greater in the impaired old rats than in the unimpaired old rats. The sensitivity of cortical neurones to glutamate was unaffected by age. There were also significant correlations between the percentages of cortical neurones responding to ACh and bicuculline and different parameters of water maze acquisition during days 7-8, but not during days 2-3, when spatial learning had not begun, and days 13-14, when spatial learning was complete. Biochemical and morphological analyses did not show any significant differences in ChAT activity and AChE-positive fibre density in the frontoparietal cortices of the three groups of rats. The results demonstrate that the learning deficit observed in old age rats cannot be adequately explained solely by a reduction in cholinergic receptor sensitivity and that an age-related increase in GABAergic tone may be a more important determinant of cognitive impairment.
本研究调查了3 - 4月龄和21月龄大鼠在莫里斯水迷宫中的表现，并将与年龄相关的认知缺陷与额叶皮质胆碱能和γ-氨基丁酸能系统的变化相关联。根据老年大鼠在水迷宫中寻找隐藏水下平台的能力，将其分为两组，即未受损老年组和受损老年组，用于电生理、神经化学和形态学研究。在乌拉坦麻醉下，从额叶皮质的运动区记录额叶皮质神经元的放电率，发现与年轻大鼠相比，两组老年大鼠的放电率明显较慢，但两组老年大鼠之间没有差异。受损和未受损老年组额叶皮质神经元对乙酰胆碱和卡巴胆碱的敏感性明显低于年轻组，但两组老年大鼠之间没有差异。相反，与年轻大鼠相比，老年大鼠额叶皮质神经元对荷包牡丹碱的敏感性明显更高，且受损老年大鼠的敏感性明显高于未受损老年大鼠。皮质神经元对谷氨酸的敏感性不受年龄影响。在第7 - 8天（而非第2 - 3天，此时空间学习尚未开始；以及第13 - 14天，此时空间学习已完成），对乙酰胆碱和荷包牡丹碱有反应的皮质神经元百分比与水迷宫获取的不同参数之间也存在显著相关性。生化和形态学分析未显示三组大鼠额顶叶皮质中胆碱乙酰转移酶活性和乙酰胆碱酯酶阳性纤维密度有任何显著差异。结果表明，老年大鼠中观察到的学习缺陷不能仅通过胆碱能受体敏感性降低来充分解释，与年龄相关的γ-氨基丁酸能张力增加可能是认知障碍更重要的决定因素。
