Valastro B, Ghribi O, Poirier J, Krzywkowski P, Massicotte G
Département de Chimie-Biologie, Université du Québec à Trois-Rivières, C.P. 500, Trois-Rivières, Québec, Canada G9A 5H7.
Neurobiol Aging. 2001 Jan-Feb;22(1):9-15. doi: 10.1016/s0197-4580(00)00177-9.
In the present study, modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors by phosphatidylserine (PS) and synaptic plasticity were investigated in the hippocampus of young (4-month-old) and aged (18-month-old) apolipoprotein E (apoE)-deficient mice. Qualitative as well as quantitative analysis of brain sections in both young and aged apoE-deficient mice did not reveal any substantial changes of AMPA receptor binding in the various hippocampal regions, compared to age-matched controls. Nevertheless, enhancement of AMPA receptor binding elicited by PS treatment was found to be abolished in most hippocampal regions of young apoE-deficient mice, while modulation of AMPA receptors by this phospholipid was not significantly altered in the hippocampal formation of aged apoE-deficient animals. At the electrophysiological level, long-term potentiation (LTP) induced by theta burst stimulation was lower in area CA1 of the hippocampus of young, but not aged, apoE-deficient mice compared to age-matched controls. These results confirm that apoE is important for AMPA receptor regulation and LTP expression in the hippocampal formation. However, the presence of LTP in aged apoE-deficient animals, together with apparent recovery of the PS action on AMPA receptors, suggests that aged apoE-knockout mice possess compensatory mechanisms that reduce biochemical and electrophysiological alterations of glutamatergic neurons.
在本研究中，我们在年轻（4个月大）和老年（18个月大）的载脂蛋白E（apoE）缺陷小鼠的海马体中，研究了磷脂酰丝氨酸（PS）对α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体的调节作用以及突触可塑性。与年龄匹配的对照相比，对年轻和老年apoE缺陷小鼠脑切片的定性和定量分析均未发现海马体各区域AMPA受体结合有任何实质性变化。然而，发现PS处理引起的AMPA受体结合增强在年轻apoE缺陷小鼠的大多数海马区域中被消除，而在老年apoE缺陷动物的海马结构中，这种磷脂对AMPA受体的调节没有明显改变。在电生理水平上，与年龄匹配的对照相比，年轻（而非老年）apoE缺陷小鼠海马体CA1区由theta爆发刺激诱导的长时程增强（LTP）较低。这些结果证实apoE对海马结构中AMPA受体调节和LTP表达很重要。然而，老年apoE缺陷动物中存在LTP，以及PS对AMPA受体作用的明显恢复，表明老年apoE基因敲除小鼠具有补偿机制，可减少谷氨酸能神经元的生化和电生理改变。
