The effects of early-life immune activation on microglia-mediated neuronal remodeling and the associated ontogeny of hippocampal-dependent learning in juvenile rats.
The effects of early-life immune activation on microglia-mediated neuronal remodeling and the associated ontogeny of hippocampal-dependent learning in juvenile rats.
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DOI：
10.1016/j.bbi.2021.06.004
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Schwarz JM
中科院分区：
文献类型：
--
作者：
Osborne BF;Beamish SB;Schwarz JM
许多神经发育障碍和相关的学习缺陷与生命早期的免疫激活或持续的免疫失调有关（；O’Connor 等，2014）。神经科学家已经开始了解神经回路的成熟如何导致认知和学习行为的出现；然而，我们对这些发育中的神经回路如何受到某些事件（包括生命早期免疫激活和免疫失调等危险因素）的干扰知之甚少。为了回答这些问题，我们使用特征明确的海马依赖性学习任务，研究了生命早期免疫激活对幼年雄性和雌性大鼠海马依赖性学习出现的影响，并研究了海马中可能导致这些学习缺陷的相应动态多细胞相互作用。我们发现，即使是低水平的免疫激活也会在几天后导致海马依赖性学习缺陷，但前提是这种激活发生在发育的敏感时期。海马体中的初始免疫反应和相关细胞因子的产生在 24 小时内解决，也就是观察到的学习缺陷之前的几天，但值得注意的是，初始免疫反应之后发生了小胶质细胞-神经元通讯的改变和突触重塑，从而改变了青少年大脑发育这一时期海马神经元的结构。我们的结论是，海马发育敏感时期的免疫激活或失调可以通过多细胞过程加速学习缺陷的出现，该过程可能是由初始细胞因子反应引发的，但不是直接结果。
Many neurodevelopmental disorders and associated learning deficits have been linked to early-life immune activation or ongoing immune dysregulation (; O’Connor et al., 2014). Neuroscientists have begun to understand how the maturation of neural circuits allows for the emergence of cognitive and learning behaviors; yet we know very little about how these developing neural circuits are perturbed by certain events, including risk-factors such as early-life immune activation and immune dysregulation. To answer these questions, we examined the impact of early-life immune activation on the emergence of hippocampal-dependent learning in juvenile male and female rats using a well-characterized hippocampal-dependent learning task and we investigated the corresponding, dynamic multicellular interactions in the hippocampus that may contribute to these learning deficits. We found that even low levels of immune activation can result in hippocampal-depedent learning deficits days later, but only when this activation occurs during a sensitive period of development. The initial immune response and associated cytokine production in the hippocampus resolved within 24 hours, several days prior to the observed learning deficit, but notably the initial immune response was followed by altered microglial-neuronal communication and synapse remodeling that changed the structure of hippocampal neurons during this period of juvenile brain development. We conclude that immune activation or dysregulation during a sensitive period of hippocampal development can precipitate the emergence of learning deficits via a multi-cellular process that may be initiated by, but not the direct result of the initial cytokine response.
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DOI：
10.1073/pnas.0402680101
发表时间：
2004-05-25
影响因子：
11.1
作者：
Gogtay, N;Giedd, JN;Thompson, PM
通讯作者：
Thompson, PM
早期生活节目和神经发育障碍。
影响因子：
10.6
作者：
Bale, Tracy L.;Baram, Tallie Z.;Brown, Alan S.;Goldstein, Jill M.;Insel, Thomas R.;McCarthy, Margaret M.;Nemeroff, Charles B.;Reyes, Teresa M.;Simerly, Richard B.;Susser, Ezra S.;Nestler, Eric J.
通讯作者：
Nestler, Eric J.
DOI：
10.1073/pnas.95.18.10896
发表时间：
1998-09-01
影响因子：
11.1
作者：
Harrison, JK;Jiang, Y;Feng, LL
通讯作者：
Feng, LL
影响因子：
5.3
作者：
Bilbo, SD;Biedenkapp, JC;Maier, SF
通讯作者：
Maier, SF
影响因子：
3.5
作者：
Isgor, C;Sengelaub, DR
通讯作者：
Sengelaub, DR