Neuroscience Institute of the National Research Council Pisa, Italy.
Biophysics Institute of the National Research Council Pisa, Italy.
Front Aging Neurosci. 2014 Jan 23;6:1. doi: 10.3389/fnagi.2014.00001. eCollection 2014.
Brain aging is characterized by global changes which are thought to underlie age-related cognitive decline. These include variations in brain activity and the progressive increase in the concentration of soluble amyloid-β (Aβ) oligomers, directly impairing synaptic function and plasticity even in the absence of any neurodegenerative disorder. Considering the high social impact of the decline in brain performance associated to aging, there is an urgent need to better understand how it can be prevented or contrasted. Lifestyle components, such as social interaction, motor exercise and cognitive activity, are thought to modulate brain physiology and its susceptibility to age-related pathologies. However, the precise functional and molecular factors that respond to environmental stimuli and might mediate their protective action again pathological aging still need to be clearly identified. To address this issue, we exploited environmental enrichment (EE), a reliable model for studying the effect of experience on the brain based on the enhancement of cognitive, social and motor experience, in aged wild-type mice. We analyzed the functional consequences of EE on aged brain physiology by performing in vivo local field potential (LFP) recordings with chronic implants. In addition, we also investigated changes induced by EE on molecular markers of neural plasticity and on the levels of soluble Aβ oligomers. We report that EE induced profound changes in the activity of the primary visual and auditory cortices and in their functional interaction. At the molecular level, EE enhanced plasticity by an upward shift of the cortical excitation/inhibition balance. In addition, EE reduced brain Aβ oligomers and increased synthesis of the Aβ-degrading enzyme neprilysin. Our findings strengthen the potential of EE procedures as a non-invasive paradigm for counteracting brain aging processes.
大脑老化的特征是全局变化，这些变化被认为是导致与年龄相关的认知能力下降的原因。这些变化包括大脑活动的变化和可溶性淀粉样β（Aβ）寡聚物浓度的逐渐增加，即使在没有任何神经退行性疾病的情况下，也会直接损害突触功能和可塑性。考虑到与衰老相关的大脑功能下降对社会的巨大影响，迫切需要更好地了解如何预防或对抗这种情况。生活方式因素，如社交互动、运动锻炼和认知活动，被认为可以调节大脑生理机能及其对与年龄相关的病理变化的易感性。然而，仍然需要明确确定对环境刺激做出反应并可能介导其对病理性衰老的保护作用的精确功能和分子因素。为了解决这个问题，我们利用环境丰富（EE），这是一种基于增强认知、社交和运动经验来研究经验对大脑影响的可靠模型，在老年野生型小鼠中进行研究。我们通过使用慢性植入物进行体内局部场电位（LFP）记录来分析 EE 对老年大脑生理的功能后果。此外，我们还研究了 EE 对神经可塑性的分子标志物和可溶性 Aβ寡聚物水平的诱导变化。我们报告说，EE 引起了初级视觉和听觉皮层及其功能相互作用的活性的深刻变化。在分子水平上，EE 通过皮质兴奋/抑制平衡的向上移动增强了可塑性。此外，EE 减少了大脑中的 Aβ寡聚物并增加了 Aβ 降解酶 Neprilysin 的合成。我们的发现增强了 EE 程序作为对抗大脑衰老过程的非侵入性范例的潜力。
