Laboratório de Neurotrauma e Biomarcadores - Departamento de Bioquímica, Programa de Pós-Graduação em Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil; Centro Universitário Metodista - Instituto Porto Alegre (IPA), Porto Alegre, Brazil.
Laboratório de Neurotrauma e Biomarcadores - Departamento de Bioquímica, Programa de Pós-Graduação em Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil.
Behav Brain Res. 2021 Apr 23;404:113163. doi: 10.1016/j.bbr.2021.113163. Epub 2021 Feb 4.
Anxiety disorders are linked to mitochondrial dysfunction and decreased neurotrophic support. Since anxiolytic drugs target mitochondria, non-pharmacological approaches to improve mitochondrial metabolism such as intermittent fasting (IF) may cause parallel behavioral benefits against anxiety disorders. Here, we investigated whether a chronic IF regimen could induce anxiolytic-like effects concomitantly to modulation in mitochondrial bioenergetics and trophic signaling in mice brain. A total of 44 Male C57BL/6 J mice (180 days old) were assigned to two dietary regimens: a normal, ad libitum diet (AL group) and an alternate-day fasting (IF group), where animals underwent 10 cycles of 24 h food restriction followed by 24 h ad libitum access. Animals underwent the open field test, dark/light box and elevated plus maze tasks. Isolated nerve terminals were obtained from mice brain and used for mitochondrial respirometry, hydrogen peroxide production and assessment of membrane potential dynamics, calcium handling and western blotting. We showed that IF significantly alters total daily food intake and food consumption patterns but not body weight. There were no differences in the exploratory and locomotory parameters. Remarkably, animals from IF showed decreased anxiety-like behavior. Mitochondrial metabolic responses in different coupling states and parameters linked with HO production, Ca buffering and electric gradient were not different between groups. Finally, no alterations in molecular indicators of apoptotic death (Bax/Bcl-2 ratio) and neuroplasticity (proBDNF/BDNF and synaptophysin were observed). In conclusion, IF exerts anxiolytic-like effect not associated with modulation in synaptic neuronergetics or expression of neurotrophic proteins. These results highlight a potential benefit of intermittent fasting as a nutritional intervention in anxiety-related disorders.
焦虑症与线粒体功能障碍和神经营养支持减少有关。由于抗焦虑药物的作用靶点是线粒体，因此改善线粒体代谢的非药物方法，如间歇性禁食（IF），可能会对焦虑症产生类似的行为益处。在这里，我们研究了慢性 IF 方案是否可以在调节小鼠大脑中线粒体生物能和营养信号的同时诱导抗焦虑样效应。总共 44 只雄性 C57BL/6J 小鼠（180 天大）被分配到两种饮食方案中：正常，随意饮食（AL 组）和隔日禁食（IF 组），其中动物经历了 10 个 24 小时的禁食周期，随后是 24 小时随意进食。动物进行了旷场测试、黑暗/光亮箱和高架十字迷宫任务。从老鼠大脑中分离出神经末梢，用于线粒体呼吸测定、过氧化氢产生以及评估膜电位动力学、钙处理和蛋白质印迹。我们表明，IF 显著改变了总日摄食量和食物消耗模式，但不改变体重。探索和运动参数没有差异。值得注意的是，IF 组动物的焦虑样行为减少。不同偶联状态下的线粒体代谢反应以及与 HO 产生、Ca 缓冲和电梯度相关的参数在各组之间没有差异。最后，没有观察到凋亡死亡（Bax/Bcl-2 比值）和神经可塑性（proBDNF/BDNF 和突触小体素）的分子指标的改变。总之，IF 产生抗焦虑样效应，与突触神经元能和神经营养蛋白表达的调节无关。这些结果强调了间歇性禁食作为一种与焦虑相关疾病的营养干预的潜在益处。
