Serine hydroxymethyltransferases (SHMTs) are key enzymes in one-carbon metabolism, with vertebrates possessing two paralogs, cytosolic SHMT1 and mitochondrial SHMT2, implicated in nucleotide biosynthesis and glycine metabolism. In this study, we investigate the evolutionary history of animal Shmt genes and analyze the expression patterns of Shmt genes in developing amphioxus (Branchiostoma lanceolatum). Phylogenetic analyses indicate the presence of Shmt1 and Shmt2 orthologs in deuterostomes, spiralians and placozoans, which is consistent with an ancient Shmt gene duplication event predating bilaterian diversification. Gene expression analyses in developing amphioxus show that Shmt2 expression is confined to the somites and absent from neural tissues. In contrast, Shmt1 is broadly expressed across germ layers, but its transcription is restricted to tissues characterized by strong cell proliferation. Notably, Shmt1 expression in the nervous system does not match the distribution of glycinergic neuron populations, implying a negligible role in glycine neurotransmitter synthesis. Instead, the spatial correlation of Shmt1 expression with mitotically active domains suggests a primary function in nucleotide biosynthesis via one-carbon metabolism. These findings indicate that SHMTs predominantly support cell proliferation rather than neurotransmission in amphioxus.

In this review we propose a mechanism by which the antisecretory factor AF may decrease vertigo symptoms in Menière’s disease patients. This review is based on our previously published work and suggests a way of interpretation of the results obtained in view of the clinical effect of AF factor against vertigo caused by Menière’s disease. The Antisecretory Factor (AF) is an endogenous protein regulating water and ion transport across cellular membranes. AF was originally discovered and isolated from rat and pig pituitary gland but later it has been isolated from all mammalian and non-mammalian tissues examined. It has shown positive effects in patients with Mb Crohn, Colitis Ulcerosa and Mastitis with regression of clinical symptoms and inflammatory parameters. AF is also effective in suppressing traumatically induced increases of intra-cranial pressure (ICP). Another interesting activity of this protein is its anti-vertigo action in patients with Menière’s disease. We studied rat cerebellar granule cells in culture and demonstrated increases by AF of the inhibitory current activated by GABA at synapses. This implies strong inhibition of cerebellar granule cells in situ. The connection of cerebellum to other brain areas would finally result in activation of vestibular Deiters’ neurons in the brainstem, controlling antigravity neurons in the spinal cord. These actions may contribute to counteracting vertigo in Menière’s disease. AbstractSection Graphical abstract