Takillah Samir, Naudé Jérémie, Didienne Steve, Sebban Claude, Decros Brigitte, Schenker Esther, Spedding Michael, Mourot Alexandre, Mariani Jean, Faure Philippe
Team Neurophysiology and Behavior, Institut de Biologie Paris Seine (IBPS), UMR 8246 Neuroscience Paris Seine (NPS), Sorbonne Universités, Université Pierre et Marie Curie (UPMC), CNRS, INSERM, U1130Paris, France.
Team Brain Development, Repair and Ageing, Institut de Biologie Paris Seine (IBPS), UMR 8256 Biological Adaptation and Ageing (B2A), Sorbonne Universités, Université Pierre et Marie Curie (UPMC), CNRSParis, France.
Front Aging Neurosci. 2017 Sep 21;9:295. doi: 10.3389/fnagi.2017.00295. eCollection 2017.
Anxiolytic drugs are widely used in the elderly, a population particularly sensitive to stress. Stress, aging and anxiolytics all affect low-frequency oscillations in the hippocampus and prefrontal cortex (PFC) independently, but the interactions between these factors remain unclear. Here, we compared the effects of stress (elevated platform, EP) and anxiolytics (diazepam, DZP) on extracellular field potentials (EFP) in the PFC, parietal cortex and hippocampus (dorsal and ventral parts) of adult (8 months) and aged (18 months) Wistar rats. A potential source of confusion in the experimental studies in rodents comes from locomotion-related theta (6-12 Hz) oscillations, which may overshadow the direct effects of anxiety on low-frequency and especially on the high-amplitude oscillations in the Mu range (7-12 Hz), related to arousal. Animals were restrained to avoid any confound and isolate the direct effects of stress from theta oscillations related to stress-induced locomotion. We identified transient, high-amplitude oscillations in the 7-12 Hz range ("Mu-bursts") in the PFC, parietal cortex and only in the dorsal part of hippocampus. At rest, aged rats displayed more Mu-bursts than adults. Stress acted differently on Mu-bursts depending on age: it increases vs. decreases burst, in adult and aged animals, respectively. In contrast DZP (1 mg/kg) acted the same way in stressed adult and age animal: it decreased the occurrence of Mu-bursts, as well as their co-occurrence. This is consistent with DZP acting as a positive allosteric modulator of GABA receptors, which globally potentiates inhibition and has anxiolytic effects. Overall, the effect of benzodiazepines on stressed animals was to restore Mu burst activity in adults but to strongly diminish them in aged rats. This work suggests Mu-bursts as a neural marker to study the impact of stress and DZP on age.
抗焦虑药物在老年人中广泛使用，这是一个对压力特别敏感的人群。压力、衰老和抗焦虑药物都会独立影响海马体和前额叶皮质（PFC）中的低频振荡，但这些因素之间的相互作用仍不清楚。在这里，我们比较了压力（高架平台，EP）和抗焦虑药物（地西泮，DZP）对成年（8个月）和老年（18个月）Wistar大鼠的PFC、顶叶皮质和海马体（背侧和腹侧部分）细胞外场电位（EFP）的影响。啮齿动物实验研究中一个潜在的混淆来源是与运动相关的θ（6-12赫兹）振荡，它可能会掩盖焦虑对低频尤其是与觉醒相关的Mu范围（7-12赫兹）高振幅振荡的直接影响。动物被限制活动以避免任何混淆，并将压力的直接影响与压力诱导运动相关的θ振荡隔离开来。我们在PFC、顶叶皮质以及仅在海马体的背侧部分发现了7-12赫兹范围内的瞬态高振幅振荡（“Mu爆发”）。在静息状态下，老年大鼠比成年大鼠表现出更多的Mu爆发。压力对Mu爆发的作用因年龄而异：在成年动物和老年动物中，分别是增加和减少爆发。相比之下，DZP（1毫克/千克）在应激的成年和老年动物中的作用方式相同：它减少了Mu爆发的发生率及其共现情况。这与DZP作为GABA受体的正变构调节剂的作用一致，它全局增强抑制作用并具有抗焦虑作用。总体而言苯二氮䓬类药物对应激动物的影响是恢复成年动物的Mu爆发活动，但在老年大鼠中则强烈减少它们。这项工作表明Mu爆发是研究压力和DZP对年龄影响的神经标志物。
