Differential effects of aging and insulin-like growth factor-1 on synapses in CA1 of rat hippocampus

Differential effects of aging and insulin-like growth factor-1 on synapses in CA1 of rat hippocampus
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DOI:
10.1093/cercor/bhh158
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发表时间:
2005-05-01
期刊:
影响因子:
3.7
通讯作者:
Brunso-Bechtold, JK
Brunso-Bechtold, JK
中科院分区:
医学2区
文献类型:
--
作者:
Shi, L;Linville, MC;Brunso-Bechtold, JK

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侧脑室注射胰岛素样生长因子-1(IGF-1)28天可改善老年大鼠学习记忆能力的老化。本研究调查是否有一个老化相关的突触在海马CA 1区辐射层的下降,以及是否IGF-1可以改善这种下降。5只年轻(4个月)、5只中年(18个月)和5只老年(29个月)Fischer 344 xBrown Norway大鼠接受盐水输注; 5只老年(29个月)大鼠在处死前接受IGF-1输注28天。应用物理解剖技术对CA 1区锥体神经元、总突触轮廓以及多棘结(MSB)复合体中的突触轮廓进行体视学定量,并测定突触后密度(PSD)长度。结果表明,突触总数在中、老年之间减少,但PSD长度和MSB突触在整个生命过程中保持不变。IGF-1输注老年大鼠并没有扭转总突触的衰老相关的下降,但增加PSD长度和MSB突触的数量。突触构型的这些变化是突触功效增强的形态学相关物。因此,衰老和IGF-1影响海马CA 1区突触的不同但互补的方面。
Aging-related impairments of learning and memory can be ameliorated by 28 days of intracerebroventricular (icv) infusion of insulin-like growth factor-1 (IGF-1) in old rats. The present study investigated whether there is an aging-related synaptic decline in the stratum radiatum of hippocampal CA1 and whether IGF-1 can ameliorate that decline. Five young (4 months), five middle-aged (18 months) and five old (29 months) Fischer 344xBrown Norway rats received saline infusion; five old (29 months) rats received IGF-1 infusion for 28 days preceding sacrifice. Pyramidal neurons, total synaptic profiles as well as synaptic profiles in multiple spine bouton (MSB) complexes in CA1 were quantified stereologically with the physical disector technique and the postsynaptic density (PSD) length was determined as well. The results indicated a decrease of total synapses between middle and old age but a maintenance of PSD length and MSB synapses throughout life. IGF-1 infusion in old rats did not reverse the aging-related decline in total synapses but did increase PSD length and the number of MSB synapses. These changes in synaptic configurations are morphological correlates of enhanced synaptic efficacy. Thus, aging and IGF-1 affect different, but complementary, aspects of synapses in hippocampal CA1.