Nicotinamide mononucleotide (NMN) and NMN-rich product supplementation alleviate p-chlorophenylalanine-induced sleep disorders

Nicotinamide mononucleotide (NMN) has various beneficial effects, while its protective effects against insomnia remain elusive. NMN and NMN-rich products (NMNP) alleviated depression-like behavior and stimulated sodium pentobarbital-induced sleeping of p-chlorophenylalanine (PCPA)-induced mice. NMN and NMNP restored brain damages and reduced oxidative stress. NAD+ concentration, silent mating type information regulation 2 homolog 1 (SIRT1) expression, 5-hydroxytryptamine (5-HT) level and 5-HT1A expression in hippocampus of PCPA-induced mice were up-regulated by NMN and NMNP. NMN and NMNP also modulated γ-gminobutyric acid (GABA) and glutamate production by increasing GABAA receptor α2 and glutamic acid decarboxylase 65/67 expression. NMNP, composed 23.9% of NMN, was more powerful than NMN in activating GABAergic system. NMN and NMNP exhibited prominent enhancement on immune system through boosting NO secretion and IL-1β expression. These data suggested that NMN and NMNP exerted sedative effects via regulating oxidative stress, SIRT1 pathway, 5-HTergic, GABAergic and immune systems simultaneously.