Galanin fiber hyperinnervation preserves neuroprotective gene expression in cholinergic basal forebrain neurons in Alzheimer's disease.
Galanin fiber hyperinnervation preserves neuroprotective gene expression in cholinergic basal forebrain neurons in Alzheimer's disease.
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DOI：
10.3233/jad-2009-1196
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Mufson EJ
中科院分区：
文献类型：
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作者：
Counts SE;He B;Che S;Ginsberg SD;Mufson EJ
在晚期阿尔茨海默病(AD)中，含有甘丙肽(GAL)的纤维高度支配胆碱能基底前脑(CBF)基底核神经元，但这种现象的分子后果尚不清楚。为了确定GAL是否改变了AD患者脑血流量细胞存活的关键基因的表达，采用单细胞微阵列分析方法，比较了临床诊断为无认知损害死亡的AD患者和缺乏GAL高神经支配(AD/GAL−)或显著GAL高神经支配(AD/GAL+)的AD患者中缺乏GAL神经支配的基底核神经元的基因表达水平。与正常对照组和AD/GAL+神经元相比，AD/Gal−基底核神经元中编码神经保护蛋白GluR2Ca~(2+)不通透性谷氨酸受体亚单位、超氧化物歧化酶2和葡萄糖转运蛋白的mRNAs水平显著降低。相反，与正常对照组和AD/GAL+神经元相比，AD/GAL−组编码可能与AD细胞死亡有关的钙蛋白酶催化和调节亚基的mRNAs增加。因此，半乳糖纤维的过度神经支配似乎保护了多条神经保护通路的基因表达，这表明半乳糖过度表达调节了AD患者CBF神经元的存活。
Fibers containing galanin (GAL) hyperinnervate cholinergic basal forebrain (CBF) nucleus basalis neurons in late stage Alzheimer’s disease (AD), yet the molecular consequences of this phenomenon are unknown. To determine whether GAL alters the expression of genes critical to CBF cell survival in AD, single cell microarray analysis was used to determine mRNA levels within nucleus basalis neurons lacking GAL innervation from subjects who died with a clinical diagnosis of no cognitive impairment (NCI) compared to nucleus basalis neurons from AD cases either lacking GAL hyperinnervation (AD/GAL−) or those displaying prominent GAL hyperinnervation (AD/GAL+). Levels of mRNAs encoding putatively neuroprotective proteins such as the GluR2 Ca2+-impermeable glutamate receptor subunit, superoxide dismutase 2, and the GLUT2 glucose transporter were significantly decreased in AD/GAL− nucleus basalis neurons compared to NCI and AD/GAL+ neurons. By contrast, mRNAs encoding calpain catalytic and regulatory subunits, which may contribute to cell death in AD, were increased in AD/GAL−compared to NCI and AD/GAL+ neurons. Hence, GAL fiber hyperinnervation appears to preserve the expression of genes subserving multiple neuroprotective pathways suggesting that GAL overexpression regulates CBF neuron survival in AD.