Blake David T, Terry Alvin V, Plagenhoef Marc, Constantinidis Christos, Liu Ruifeng
Brain and Behavior Discovery Institute, Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Commun Integr Biol. 2017 Nov 26;10(5-6):e1389359. doi: 10.1080/19420889.2017.1389359. eCollection 2017.
The brain's cholinergic arousal pathways decline in parallel with the brain's executive functions in aging and Alzheimer's Disease. The frontline and currently most effective approach to treating Alzheimer's disease is the administration of cholinesterase inhibitors, which, in a dose dependent manner, improve the symptoms of cognitive decline over the first months of treatment before further decline occurs. We recently showed that intermittent deep brain stimulation of the nucleus basalis of Meynert improves working memory function in young adult monkeys, and that this improvement depended on cholinergic function. Within minutes, the monkeys' ability to remember stimuli over a delay period improved. Over months, the monkeys performed the working memory task better even in the absence of stimulation. Here, we show historical data from our monkey colony in which more than two dozen animals have performed the same behavioral task to asymptotic performance levels. Using a distribution based on our historical data, we estimate that the monkeys receiving intermittent stimulation leapt over the performance level of 32-44 percent of peer animals in the first several months after stimulation was initiated. Implications for a parallel increase in cognitive function for early Alzheimer's patients are discussed.
在衰老和阿尔茨海默病中，大脑的胆碱能觉醒通路与大脑的执行功能同步衰退。治疗阿尔茨海默病的一线且目前最有效的方法是给予胆碱酯酶抑制剂，其以剂量依赖的方式在治疗的最初几个月改善认知衰退症状，直至进一步衰退发生。我们最近发现，对梅纳特基底核进行间歇性深部脑刺激可改善成年猕猴的工作记忆功能，且这种改善依赖于胆碱能功能。在数分钟内，猕猴在延迟期记住刺激的能力得到改善。在数月时间里，即使在没有刺激的情况下，猕猴执行工作记忆任务的表现也更好。在此，我们展示了来自我们猕猴群体的历史数据，其中二十多只动物都执行了相同的行为任务并达到渐近表现水平。基于我们的历史数据分布，我们估计接受间歇性刺激的猕猴在刺激开始后的最初几个月内，其表现超过了32%至44%的同龄动物。文中还讨论了对早期阿尔茨海默病患者认知功能平行增加的影响。
