Baram Tallie Z, Birnie Matthew T
Department of Pediatrics, University of California-Irvine, Irvine, CA, USA.
Department of Anatomy/Neurobiology, University of California-Irvine, Irvine, CA, USA.
Neurobiol Stress. 2024 Aug 30;33:100669. doi: 10.1016/j.ynstr.2024.100669. eCollection 2024 Nov.
Adverse early life experiences are strongly associated with reduced cognitive function throughout life. The link is strong in many human studies, but these do not enable assigning causality, and the limited access to the live human brain can impede establishing the mechanisms by which early-life adversity (ELA) may induce cognitive problems. In experimental models, artificially imposed chronic ELA/stress results in deficits in hippocampus dependent memory as well as increased vulnerability to the deleterious effects of adult stress on memory. This causal relation of ELA and life-long memory impairments provides a framework to probe the mechanisms by which ELA may lead to human cognitive problems. Here we focus on the consequences of a one-week exposure to adversity during early postnatal life in the rodent, the spectrum of the ensuing memory deficits, and the mechanisms responsible. We highlight molecular, cellular and circuit mechanisms using convergent trans-disciplinary approaches aiming to enable translation of the discoveries in experimental models to the clinic.
早期生活中的不良经历与一生中认知功能的下降密切相关。这一联系在许多人体研究中都很明显，但这些研究无法确定因果关系，而且由于难以直接研究活体人类大脑，阻碍了我们建立早期生活逆境（ELA）可能导致认知问题的机制。在实验模型中，人为施加的慢性ELA/应激会导致海马体依赖性记忆缺陷，以及成年后应激对记忆的有害影响的易感性增加。ELA与终生记忆损伤之间的这种因果关系为探究ELA可能导致人类认知问题的机制提供了一个框架。在这里，我们关注啮齿动物出生后早期一周暴露于逆境的后果、随之而来的记忆缺陷范围以及相关机制。我们使用跨学科的方法突出分子、细胞和神经回路机制，旨在将实验模型中的发现转化应用于临床。
