In humans, early-life adversity is associated with impairments in learning and memory that may emerge later in life. In rodent models, early-life adversity directly impacts hippocampal neuron structure and connectivity with progressive deficits in long-term potentiation and spatial memory function. Previous work has demonstrated that augmented release and actions of the stress-activated neuropeptide, CRH, contribute to the deleterious effects of early-life adversity on hippocampal dendritic arborization, synapse number and memory-function. Early-life adversity increases hippocampal CRH expression, and blocking hippocampal CRH receptor type-1 (CRHR1) immediately following early-life adversity prevented the consequent memory and LTP defects. Here, we tested if blocking CRHR1 in young adults ameliorates early-life adversity-provoked memory deficits later in life. A weeklong course of a CRHR1 antagonist in 2-month-old male rats prevented early-life adversity-induced deficits in object recognition memory that emerged by 12 months of age. Surprisingly, whereas the intervention did not mitigate early-life adversity-induced spatial memory losses at 4 and 8 months, it restored hippocampus-dependent location memory in 12-month-old rats that experienced early-life adversity. Neither early-life adversity nor CRHR1 blockade in the adult influenced anxiety- or depression-related behaviors. Altogether, these findings suggest that cognitive deficits attributable to adversity during early-life-sensitive periods are at least partially amenable to interventions later in life.

中文翻译：

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阻断成人的 CRH 受体可以减轻因早年逆境引起的与年龄相关的记忆障碍。

对于人类来说，早年的逆境与晚年可能出现的学习和记忆障碍有关。在啮齿动物模型中，早年的逆境直接影响海马神经元的结构和连接性，并导致长期增强和空间记忆功能的渐进性缺陷。先前的研究表明，应激激活的神经肽 CRH 的释放和作用增强，会导致早年逆境对海马树突树枝化、突触数量和记忆功能产生有害影响。早年的逆境会增加海马 CRH 的表达，在早年的逆境后立即阻断海马 CRH 受体 1 型 (CRHR1) 可以防止随之而来的记忆和 LTP 缺陷。在这里，我们测试了阻断年轻人的 CRHR1 是否可以改善早年逆境引发的晚年记忆缺陷。对 2 个月大的雄性大鼠进行为期一周的 CRHR1 拮抗剂疗程，可预防 12 个月大时出现的早年逆境引起的物体识别记忆缺陷。令人惊讶的是，虽然干预措施并没有减轻 4 个月和 8 个月大时因早年逆境引起的空间记忆丧失，但它却恢复了经历早年逆境的 12 个月大大鼠的海马依赖性位置记忆。早年的逆境和成年后的 CRHR1 阻断都不会影响焦虑或抑郁相关的行为。总而言之，这些研究结果表明，早年敏感时期逆境造成的认知缺陷至少部分可以在以后的生活中进行干预。