Butkevich Irina P, Mikhailenko Viktor A, Vershinina Elena A, Barr Gordon A
Laboratory of Ontogenesis of the Nervous System, Pavlov Institute of Physiology, Russian Academy of Sciences, Saint Petersburg, Russia.
Department of Information Technologies and Mathematical Modeling, Pavlov Institute of Physiology, Russian Academy of Sciences, Saint Petersburg, Russia.
Front Behav Neurosci. 2021 Jul 21;15:691578. doi: 10.3389/fnbeh.2021.691578. eCollection 2021.
Exposure to stress at an early age programs the HPA axis which can lead to cognitive deficits in adults. However, it is not known whether these deficits emerge in adulthood or are expressed earlier in life. The aims of the study were to investigate (1) the immediate effects of early injury-induced stress in one-day-old (P1) and repeated stress on at P1 and P2 rat pups on plasma corticosterone levels; and (2) examine the subsequent long-term effects of this early stress on spatial learning and memory, and stress reactivity in early P26-34 and late P45-53 adolescent male and female rats. Intra-plantar injection of formalin induced prolonged and elevated levels of corticosterone in pups and impaired spatial learning and short- and long-term memory in late adolescent males and long-term memory in early adolescent females. There were sex differences in late adolescence in both learning and short-term memory. Performance on the long-term memory task was better than that on the short-term memory task for all early adolescent male and female control and stressed animals. Short-term memory was better in the late age control rats of both sexes and for formalin treated females as compared with the early age rats. These results are consistent with an impaired function of structures involved in memory (the hippocampus, amygdala, prefrontal cortex) after newborn pain. However, activation of the HPA axis by neonatal pain did not directly correlate with spatial learning and memory outcomes and the consequences of neonatal pain remain are likely multi-determined.
早年暴露于应激会对下丘脑-垂体-肾上腺（HPA）轴产生影响，这可能导致成年后出现认知缺陷。然而，尚不清楚这些缺陷是在成年期出现还是在生命早期就已表现出来。本研究的目的是调查：（1）一日龄（P1）大鼠早期损伤诱导应激以及P1和P2期大鼠反复应激对血浆皮质酮水平的即时影响；（2）研究这种早期应激对P26 - 34期和P45 - 53期青春期雄性和雌性大鼠空间学习和记忆以及应激反应性的后续长期影响。足底注射福尔马林可使幼崽体内皮质酮水平持续升高，并损害青春期晚期雄性大鼠的空间学习以及短期和长期记忆，以及青春期早期雌性大鼠的长期记忆。在青春期晚期，学习和短期记忆均存在性别差异。对于所有青春期早期的雄性和雌性对照及应激动物，长期记忆任务的表现均优于短期记忆任务。与早期大鼠相比，两性的晚期对照大鼠以及福尔马林处理的雌性大鼠的短期记忆更好。这些结果与新生疼痛后记忆相关结构（海马体、杏仁核、前额叶皮质）功能受损一致。然而，新生儿疼痛对HPA轴的激活与空间学习和记忆结果并无直接关联，新生儿疼痛的后果可能是多因素决定的。
