Squalamine reverses age-associated changes of firing patterns of myenteric sensory neurons and vagal fibres.

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 changed aged neurons firing patterns to a young phenotype. In contrast to young neurons, sertraline failed to increase firing rates in the aged vagus whereas squalamine was effective. These results may have implications for improved treatments involving pharmacological and electrical stimulation of the vagus for age-related mood and other disorders. For example, oral squalamine might be substituted for or added to sertraline for the aged.

Adolescence, the Microbiota-Gut-Brain Axis, and the Emergence of Psychiatric Disorders.

Second only to early life, adolescence is a period of dramatic change and growth. For the developing young adult, this occurs against a backdrop of distinct environmental challenges and stressors. A significant body of work has identified an important role for the microbiota-gut-brain (MGB) axis in the development and function of the brain. Given that the MGB axis is both highly plastic during the teenage years and vulnerable to environmental stressors, more attention needs to be drawn to its potential role in the emergence of psychiatric illnesses, many of which first manifest during adolescence. Here, we review the current literature surrounding the developing microbiome, enteric nervous system, vagus nerve, and brain during the adolescent period. We also examine preclinical and clinical research involving the MGB axis during this dynamic developmental window and argue that more research is needed to further understand the role of the MGB in the pathogenesis of brain disorders. Greater understanding of the adolescent MGB axis will open up the exciting potential for new microbial-based therapeutics for the treatment of these often-refractory psychiatric illnesses.