Craig M C, Fletcher P C, Daly E M, Rymer J, Brammer M, Giampietro V, Stahl D, Maki P M, Murphy Declan G M
Department of Psychological Medicine, Section of Brain Maturation, Institute of Psychiatry, Kings College London, Denmark Hill, London, UK.
Horm Behav. 2009 Jan;55(1):41-9. doi: 10.1016/j.yhbeh.2008.08.008. Epub 2008 Aug 28.
Recent evidence suggests that loss of ovarian function following ovariectomy is a risk factor for Alzheimer's disease (AD); however, the biological basis of this risk remains poorly understood. We carried out an fMRI study into the interaction between loss of ovarian function (after Gonadotropin Hormone Releasing Hormone agonist (GnRHa) treatment) and scopolamine (a cholinergic antagonist used to model the memory decline associated with aging and AD). Behaviorally, cholinergic depletion produced a deficit in verbal recognition performance in both GnRHa-treated women and wait list controls, but only GnRHa-treated women made more false positive errors with cholinergic depletion. Similarly, cholinergic depletion produced a decrease in activation in the left inferior frontal gyrus (LIFG; Brodmann area 45)--a brain region implicated in retrieving word meaning--in both groups, and activation in this area was further reduced following GnRHa treatment. These findings suggest biological mechanisms through which ovarian hormone suppression may interact with the cholinergic system and the LIFG. Furthermore, this interaction may provide a useful model to help explain reports of increased risk for cognitive decline and AD in women following ovariectomy.
近期证据表明，卵巢切除术后卵巢功能丧失是阿尔茨海默病（AD）的一个风险因素；然而，这种风险的生物学基础仍知之甚少。我们进行了一项功能磁共振成像（fMRI）研究，以探究卵巢功能丧失（促性腺激素释放激素激动剂（GnRHa）治疗后）与东莨菪碱（一种用于模拟与衰老和AD相关的记忆衰退的胆碱能拮抗剂）之间的相互作用。在行为方面，胆碱能耗竭在接受GnRHa治疗的女性和候补对照组中均导致言语识别表现出现缺陷，但只有接受GnRHa治疗的女性在胆碱能耗竭时出现更多假阳性错误。同样，胆碱能耗竭在两组中均导致左侧额下回（LIFG；布罗德曼45区）——一个与检索词义有关的脑区——的激活减少，并且在GnRHa治疗后该区域的激活进一步降低。这些发现提示了卵巢激素抑制可能与胆碱能系统和LIFG相互作用的生物学机制。此外，这种相互作用可能提供一个有用的模型，以帮助解释卵巢切除术后女性认知衰退和AD风险增加的报道。
