Gender differences in neurotrophin and glutamate receptor expression in cholinergic nucleus basalis neurons during the progression of Alzheimer's disease.
Gender differences in neurotrophin and glutamate receptor expression in cholinergic nucleus basalis neurons during the progression of Alzheimer's disease.
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DOI：
10.1016/j.jchemneu.2011.02.004
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发表时间：
2011-10
影响因子：
2.8
通讯作者：
Mufson EJ
中科院分区：
文献类型：
--
作者：
Counts SE;Che S;Ginsberg SD;Mufson EJ
老年女性阿尔茨海默病（AD）的发病率较高，表明性别在 AD 发病机制中发挥着重要作用。来自临床和药理学研究、神经病理学检查和激素替代治疗模型的证据表明，与男性相比，基底核 (NB) 内的胆碱能基底前脑 (CBF) 皮层投射神经元介导记忆和注意力，并在 AD 中退化，在老年女性中可能比男性更容易受到影响。 CBF 神经元的生存和维持依赖于神经生长因子 (NGF) 及其同源受体（trkA 和 p75NTR）。我们最近证明了 AD 进展过程中 NGF 及其受体的平衡向细胞死亡机制的转变。为了确定性别是否影响 CBF 内 NGF 信号系统的表达，我们使用单细胞 RNA 扩增和定制微阵列技术来比较宗教团体研究中男性和女性成员的组织样本中单个胆碱能 NB 神经元的基因表达谱，这些成员的死亡临床诊断为无认知障碍 (NCI)、轻度认知障碍 (MCI) 或轻度/中度 AD。在整个临床诊断过程中，雄性胆碱能 NB 神经元内的 p75NTR 表达没有变化，而女性 NB 神经元中的 p75NTR mRNA 水平在 AD 中与 NCI 相比降低了约 40%。与 NCI 和 MCI 相比，男性 AD 受试者 NB 神经元内 trkA mRNA 水平降低约 45%。相比之下，与 NCI 相比，MCI 和 AD 中女性 NB 神经元 trkA 表达均降低约 50%。 trkA mRNA 水平降低与女性受试者较差的整体认知能力和较高的 Braak 分数相关。此外，我们发现 AD 中 NB 神经元中 GluR2 AMPA 谷氨酸受体亚基表达存在女性选择性减少。这些数据表明，女性的胆碱能 NB 神经元在 AD 进展过程中可能面临更大的退化风险，并支持在该疾病的临床前阶段进行性别特异性治疗干预的概念。
The higher incidence rate of Alzheimer’s disease (AD) in elderly women indicates that gender plays a role in AD pathogenesis. Evidence from clinical and pharmacologic studies, neuropathological examinations, and models of hormone replacement therapy suggest that cholinergic basal forebrain (CBF) cortical projection neurons within the nucleus basalis (NB), which mediate memory and attention and degenerate in AD, may be preferentially vulnerable in elderly women compared to men. CBF neurons depend on nerve growth factor (NGF) and their cognate receptors (trkA and p75NTR) for their survival and maintenance. We recently demonstrated a shift in the balance of NGF and its receptors toward cell death mechanisms during the progression of AD. To address whether gender affects NGF signaling system expression within the CBF, we used single cell RNA amplification and custom microarray technologies to compare gene expression profiles of single cholinergic NB neurons in tissue specimens from male and female members of the Religious Orders Study who died with a clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), or mild/moderate AD. p75NTR expression within male cholinergic NB neurons was unchanged across clinical diagnosis, whereas p75NTR mRNA levels in female NB neurons exhibited a ~40% reduction in AD compared to NCI. Male AD subjects displayed a ~45% reduction in trkA mRNA levels within NB neurons compared to NCI and MCI. In contrast, NB neuronal trkA expression in females was reduced ~50% in both MCI and AD compared to NCI. Reduced trkA mRNA levels were associated with poorer global cognitive performance and higher Braak scores in the female subjects. In addition, we found a female-selective reduction in GluR2 AMPA glutamate receptor subunit expression in NB neurons in AD. These data suggest that cholinergic NB neurons in females may be at greater risk for degeneration during the progression of AD and support the concept of gender-specific therapeutic interventions during the preclinical stages of the disease.
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影响因子：
3.5
作者：
Gibbs, RB;Burke, AM;Johnson, DA
通讯作者：
Johnson, DA
影响因子：
5.3
作者：
Houeland, Gry;Romani, Armando;Marie, Helene
通讯作者：
Marie, Helene
影响因子：
5.3
作者：
Gibbs, RB
通讯作者：
Gibbs, RB
DOI：
10.3233/jad-2009-1196
发表时间：
2009
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Counts SE;He B;Che S;Ginsberg SD;Mufson EJ
通讯作者：
Mufson EJ
影响因子：
--
作者：
Counts, Scott E.;He, Bin;Mufson, Elliott J.
通讯作者：
Mufson, Elliott J.