Axon degeneration represents a pathological feature of many neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease where axons die before the neuronal soma, and axonopathies, such as Charcot-Marie-Tooth disease and hereditary spastic paraplegia. Over the last two decades, it has slowly emerged that a central signaling pathway forms the basis of this process in many circumstances. This is an axonal NAD-related signaling mechanism mainly regulated by the two key proteins with opposing roles: the NAD-synthesizing enzyme NMNAT2, and SARM1, a protein with NADase and related activities. The crosstalk between the axon survival factor NMNAT2 and pro-degenerative factor SARM1 has been extensively characterized and plays an essential role in maintaining the axon integrity. This pathway can be activated in necroptosis and in genetic, toxic or metabolic disorders, physical injury and neuroinflammation, all leading to axon pathology. SARM1 is also known to be involved in regulating innate immunity, potentially linking axon degeneration to the response to pathogens and intercellular signaling. Understanding this NAD-related signaling mechanism enhances our understanding of the process of axon degeneration and enables a path to the development of drugs for a wide range of neurodegenerative diseases.

Isolated gastric glands were used to study the mechanism of acid secretory inhibition by thiocyanate (SCN). It was found that SCN does not act as a competitive antagonist of histamine nor does SCN prevent the increase in cellular cAMP associated with histamine stimulation. SCN modifies but does not prevent the expansion of parietal cell canaliculi, indicating that this characteristic morphological transition does not require the actual formation of hydrochloric acid. Low doses (less than 5 mM) of SCN were found to inhibit aminopyrine accumulation, an index of acid formation, but do not inhibit either resting or stimulated respiration. Higher doses (greater than 10 mM) of SCN produce significant inhibition of stimulated but not resting respiration. These results indicate that SCN has two actions, i.e., inhibition of acid formation that requires low doses and inhibition of oxidative metabolism that requires higher doses. Incubation of glands in high-K+ (108 mM) medium leads to formation of an acid gradient in the absence of other secretagogues. The gradient was found to be transient, and its formation does not require oxidative metabolism, indicating that continued proton pumping is not required. Low doses of SCN were found to be more effective in dissipating the high-K+-induced gradient than a similar gradient induced by histamine stimulation. These results support the hypothesis that SCN inhibits acid secretion by increasing the rate of proton-gradient dissipation rather than interfering with a proton-pump mechanism.

Small and large animal models are important tools for investigating the pathogenesis of neurodegenerative diseases and developing therapeutic strategies, particularly when diseases are species-specific. Horses are affected by various neuropathies, including the highly prevalent recurrent laryngeal neuropathy (RLN) of large breeds (Draper & Piercy, 2018), sensory disorders, such as equine trigeminal-mediated head shaking syndrome (Aleman et al., 2013) and autonomic dysfunction seen in equine grass sickness (Cottrell et al., 1999). In particular, understanding the molecular and cellular basis of disorders that primarily affect long axons, might inform improved understanding of comparable disorders in humans. The recurrent laryngeal nerves (RLn) are the longest nerves in