The generation of protective BDNF necessitates identification of appropriate targets; here we considered the role of Sirt1, whose activation plays a crucial role in neuroprotection and improved cognition.[72, 73] Additionally, plasma BDNF and Sirt1 levels are positively correlated in patients with depression.[74] Lactate regulates the redox state of neurons through alteration the NAD/NADH ratio,[75] leading to activation of Sirt1 whose activity is dependent on NAD levels. This evidence concerns the gene BDNF and major depressive disorder.