Nicotinamide Mononucleotide and Melatonin Alleviate Aging-induced Cognitive Impairment via Modulation of Mitochondrial Function and Apoptosis in the Prefrontal Cortex and Hippocampus.

Given the fact that both melatonin and nicotinamide mononucleotide (NMN) act as pleiotropic agents in various age-related cognitive disorders, we aimed to investigate the effect of these compounds separately and together on the cognitive outcomes, mitochondrial function, and apoptosis in aged rats. Forty old and ten young (24 and 3 months old, respectively) male Wistar rats were randomly allocated into five groups: Young+Normal saline (NS), Aged+NS, Aged+Melatonin, Aged+NMN, and Aged+melatonin+NMN. Melatonin (10 mg/kg) and NMN (100 mg/kg) were administered, separately or in combination for 28 every other day in aged animals. The Barnes maze and novel object recognition test were used to assess spatial and episodic-like memories, respectively. Also, apoptosis and alterations in mitochondrial function including reactive oxygen species (ROS) and ATP levels as well as mitochondrial membrane potential were assessed in both prefrontal cortex (PFC) and hippocampus (HIP) regions. Behavioral results revealed that NMN and melatonin separately or in combination, alleviate aging-induced memory impairment. Moreover, agents' co-administration declined mitochondrial dysfunction and apoptotic cell count both in PFC and HIP regions. The agents separately or in combination (more potent) could induce neuroprotective effect and improve learning and memory in aged animals.