Gut-Brain rejuvenation: Identification of age associated changes in the neural firing pattern of myenteric primary afferent neurons and vagal fibres that are reversed by the aminosterol, squalamine

Abstract Vagus nerve signaling is a key component of the gut-brain axis and regulates diverse physiological processes that decline with age. Gut to brain vagus firing patterns are regulated by myenteric intrinsic primary afferent neuron (IPAN) to vagus neurotransmission. It remains unclear how IPANs or the afferent vagus age functionally. Here we identified a distinct ageing code in gut to brain neurotransmission defined by consistent differences in firing rates, burst durations, interburst and intraburst firing intervals of IPANs and the vagus, when comparing young and aged neurons. The aminosterol, squalamine, reverted aged neurons to a young phenotype indicating the age associated changes in neural firing patterns are reversable. In contrast to young neurons sertraline failed to increase firing rates in the aged vagus whereas squalamine was still effective. These results may have implications for improved treatments involving pharmacological and electrical stimulation of the vagus for age-related mood and other disorders.