University Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, Balearic Islands Health Research Institute (IdISBa), Palma, Spain; Laboratory of Neurophysiology, Department of Biology, University of the Balearic Islands, Palma, Spain.
Laboratory of Neurophysiology, Department of Biology, University of the Balearic Islands, Palma, Spain.
Neurobiol Aging. 2018 Nov;71:115-126. doi: 10.1016/j.neurobiolaging.2018.07.014. Epub 2018 Jul 29.
The aims of this study were (1) to behaviorally phenotype rats at different ages for both cognitive performance and affect, (2) to evaluate the possible beneficial effects of 8-OH-DPAT (a 5-HT receptor agonist) treatments on improving age-related behavioral deficits, and (3) to uncover putative key brain targets (e.g., Fas-associated protein with death domain [FADD] and related partners) that might contribute to the observed age-related behavioral changes. The principal results showed that acute, but not repeated, 8-OH-DPAT treatments improved age-related deficits in cognitive performance and affect while induced hypothermia. Moreover, multifunctional FADD protein decreased with age specifically in the hippocampus (as compared to the prefrontal cortex) and was further decreased following acute 8-OH-DPAT. The major conclusions indicate a parallelism between the beneficial effects observed following acute 8-OH-DPAT on improving the negative consequences of aging on cognition and affect, together with the acute induction of hypothermia and hippocampal FADD regulation. Because these effects were not observed following repeated treatment (i.e., observed tolerance to acute hypothermia), the results suggest 5-HT receptors desensitization and/or the activation of compensatory adaptive mechanisms.
(1) 在不同年龄阶段对大鼠进行认知表现和情感的行为表型分析；(2) 评估 8-OH-DPAT（5-羟色胺受体激动剂）治疗对改善与年龄相关的行为缺陷的可能有益效果；(3) 揭示可能导致观察到的与年龄相关的行为变化的潜在关键大脑靶点（例如 Fas 相关死亡结构域蛋白[FADD]和相关伙伴）。主要结果表明，急性而非重复的 8-OH-DPAT 治疗可改善认知表现和情感的与年龄相关的缺陷，同时诱导体温降低。此外，多功能 FADD 蛋白随年龄的增长而特异性减少，特别是在海马体（与前额叶皮层相比），并且在急性 8-OH-DPAT 后进一步减少。主要结论表明，在改善与年龄相关的认知和情感负面影响方面，急性 8-OH-DPAT 观察到的有益效果与急性体温降低的诱导以及海马体 FADD 调节之间存在平行关系。由于在重复治疗后未观察到这些效果（即，对急性体温降低的观察到的耐受性），结果表明 5-羟色胺受体脱敏和/或激活代偿性适应机制。
