Immune Challenge Alters Reactivity of Hippocampal Noradrenergic System in Prenatally Stressed Aged Mice
Immune Challenge Alters Reactivity of Hippocampal Noradrenergic System in Prenatally Stressed Aged Mice
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DOI：
10.1155/2019/3152129
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发表时间：
2019-01
影响因子：
3.1
通讯作者：
G. Grigoryan;N. Lonnemann;M. Korte
中科院分区：
文献类型：
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作者：
G. Grigoryan;N. Lonnemann;M. Korte
产前应激（PS）对子代中枢神经系统的形态和功能状态有长期的后遗症。PS诱导的机体促炎状态可能导致成年人海马突触可塑性和海马依赖性记忆形成受损。我们在这里解决的问题，如何PS诱导的免疫反应的变化，在年轻和老年小鼠可能有助于海马功能的变化在老龄化。免疫刺激（通过LPS注射）显著影响PS小鼠海马CA 3-CA 1突触进行长时程增强（LTP）的能力。已知影响LTP幅度的老龄PS小鼠血液中皮质酮水平升高表明由于子宫内应激暴露导致HPA轴的慢性激活。我们研究了肾上腺素能受体对老年小鼠海马突触可塑性调制的贡献，发现PS-LPS组中受损的LTP确实通过应用异丙肾上腺素（一种非特异性去甲肾上腺素能激动剂）来挽救。对所观察到的现象的机制的进一步探索将增加我们对PS和促炎免疫激活之间的相互作用及其对衰老大脑的功能和结构完整性的贡献的理解。
Prenatal stress (PS) has long-term sequelae for the morphological and functional status of the central nervous system of the progeny. A PS-induced proinflammatory status of the organism may result in an impairment of both hippocampal synaptic plasticity and hippocampus-dependent memory formation in adults. We addressed here the question of how PS-induced alterations in the immune response in young and old mice may contribute to changes in hippocampal function in aging. Immune stimulation (via LPS injection) significantly affected the ability of the hippocampal CA3-CA1 synapse of PS mice to undergo long-term potentiation (LTP). Elevated corticosterone level in the blood of aged PS mice that is known to influence LTP magnitude indicates a chronic activation of the HPA axis due to the in utero stress exposure. We investigated the contribution of adrenergic receptors to the modulation of hippocampal synaptic plasticity of aged mice and found that impaired LTP in the PS-LPS group was indeed rescued by application of isoproterenol (a nonspecific noradrenergic agonist). Further exploration of the mechanisms of the observed phenomena will add to our understanding of the interaction between PS and proinflammatory immune activation and its contribution to the functional and structural integrity of the aging brain.