Raising NAD+ With Nicotinamide Riboside Resolved Social Deficits in Autism Mouse Model
An autism model developed in male mice supplemented with nicotinamide riboside (NR) was found to have restored levels of the neurotransmitter oxytocin and improved social behavior.
Oxytocin and Mental Health
The neurotransmitter oxytocin is essential to many human behaviors such as social bonding, sexual reproduction, bonding with children and milk production [1]. Low levels of oxytocin have been implicated in autism spectrum disorder (ASD), a common and ever-growing neurodevelopmental disorder characterized by deficits in cognitive functions, as well as a difficulty in bonding and empathizing with others [2].
A new study in Nature Scientific Reports found that for male mice with depleted oxytocin (intended to model autism spectrum disorders), daily NR supplementation could restore levels of oxytocin as well as improve behavioral deficits [3].
The model mice had their gene for CD157, an important protein in the regulation of social behavior and oxytocin, “knocked-out,” or eliminated. In turn, exhibited fearful and anxiety-like behaviors, and had difficulty recognizing and interacting with other mice, which resemble the symptoms of ASD in humans.
Improving Oxytocin and Behavior
The study data demonstrated that raising NAD+ levels resolved some of the “autism-like” symptoms in male mice by repairing the production of oxytocin. The experimental mice were treated with NR, given that it has been proven to increase levels of the cellular energy carrier NAD+ both in mice and humans. The increased NAD+ helped normalize oxytocin levels in the cerebrospinal fluid in both male and female mice. In the male mice, this normalization then translated to an observed abatement of the social deficits which had developed.
Study co-author Dr. Charles Brenner shared that his team found that mice with lower levels of oxytocin demonstrated an improvement in their levels once supplemented with oral Niagen nicotinamide riboside. Once their oxytocin levels were normalized, improvements in their behavioral deficits followed suit. Specifically, the mice gained an interest in interacting with new mice and spent an increased amount of time in a new environment--characteristics that are exhibited by normal mice.
Because low oxytocin has been seen in cases of human autism, the team hopes to progress to clinical testing to determine whether NR has the potential to address this deficit and serve as a potential therapy for different forms of ASD in humans.
This was the first study to investigate the effects of NR on sociability and anxiety-like behaviors in a mouse model of autism. These findings build upon a growing body of preclinical research into the role of NAD-boosters like NR in supporting cognitive health and addressing neurodevelopmental and mood disorders.
Further research in animal models and humans is required to establish the potential for NAD+ raising agents like NR in addressing symptoms of neurodevelopmental and mood disorders such as autism and depression. Nevertheless, this study is an important step in paving the way to better understand the enigmatic and ever-growing condition of autism.