Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain.
Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain.
Behav Brain Res. 2021 Jul 9;409:113328. doi: 10.1016/j.bbr.2021.113328. Epub 2021 Apr 27.
Aging is associated with a reduced ability to identify and discriminate scents, and olfactory dysfunction has been linked to preclinical stages of neurodegenerative diseases in humans. Moreover, emerging evidence suggests that smell-driven behaviors are regulated by hormones like insulin or leptin, and by metabolic parameters like glucose, which in turn may influence monoaminergic neurotransmission in brain areas related to cognition. Several studies have suggested that dietary interventions like caloric restriction (CR) can mitigate the age-induced decline in memory by modifying metabolic parameters and brain monoaminergic levels. The present study explored the effects of CR on age-dependent olfactory memory deficits, as well as their relationship with peripheral leptin, insulin and glucose levels, and brain monoamines. To this end, aged rats (24-months-old) fed on a CR diet or with ad libitum access to food, and adult rats (3-4 months), were trained in an odor discrimination task (ODT). The peripheral plasma levels of insulin, leptin, and glucose, and of monoamines and metabolites/precursors in brain areas related to olfactory learning and memory processes, such as the striatum and frontal cortex (FC), were determined. The data obtained indicated that CR attenuated the age-dependent decline in olfactory sensitivity in old animals fed ad libitum, which was correlated with the performance in ODT retention trial, as well as with leptin plasma levels. CR enhanced dopamine levels in the striatum, while it attenuated the age-related decline in serotonin levels in the striatum and FC. Such findings support a positive effect of CR on age-dependent olfactory sensitivity decline and dysfunctions in brain monoamine levels.
衰老是识别和区分气味能力下降的原因，而嗅觉功能障碍与人类神经退行性疾病的临床前阶段有关。此外，新出现的证据表明，嗅觉驱动的行为受胰岛素或瘦素等激素以及葡萄糖等代谢参数的调节，而这些参数反过来又可能影响与认知相关的大脑区域中的单胺能神经传递。一些研究表明，通过改变代谢参数和大脑单胺能水平，像热量限制（CR）这样的饮食干预可以减轻年龄引起的记忆下降。本研究探讨了 CR 对年龄相关嗅觉记忆缺陷的影响，以及它们与外周瘦素、胰岛素和葡萄糖水平以及大脑单胺之间的关系。为此，给喂食 CR 饮食或随意进食的老年大鼠（24 个月大）和成年大鼠（3-4 个月）进行了气味辨别任务（ODT）训练。测定了与嗅觉学习和记忆过程相关的大脑区域（如纹状体和额叶皮层（FC））中的外周血浆胰岛素、瘦素和葡萄糖水平以及单胺及其代谢物/前体的水平。获得的数据表明，CR 减轻了自由进食的老年动物的年龄相关嗅觉敏感性下降，这与 ODT 保留试验中的表现以及瘦素的血浆水平相关。CR 增加了纹状体中的多巴胺水平，同时减轻了纹状体和 FC 中与年龄相关的 5-羟色胺水平下降。这些发现支持了 CR 对年龄相关嗅觉敏感性下降和大脑单胺水平功能障碍的积极影响。
