Betaine homocysteine s-methyltransferase deficiency increases susceptibility to noise-induced hearing loss correlating with plasma hyperhomocysteinemia

Resumen del póster presentado a NUTRIMAD: "Nutrición comunitaria en el siglo XXI", celebrada en Madrid del 24 al 27 de octubre de 2018.[Background] According to the World Health Organization, the incidence of auditory disorders, especially noise-induced hearing loss, isincreasing dramatically. Genetic and environmentalfactors are part of the multifactorial aetiology of hearing loss, but nutritional imbalance is an emerging contributor. Epidemiological and experimental studies have revealed a correlation between hearing loss and increased plasma homocysteine (Hcy) secondary to methionine cycle impairment. Betaine homocysteine S-methyltransferases (BHMTs) are responsible for the remethylation of Hcy, hence their malfunction leadsto hyperhomocysteinemia. [Aim] To study the cochlear expression of methionine cycle genes and the impact of Bhmt knockdown in the response to noise injury. [Materials and methods] Mouse hearing was evaluated at different ages by recording auditory brainstem responses (ABR) and following noise exposure. Cochlear cytoarchitecture was evaluated by histology and immunohistochemistry, and gene expression by RNA-arrays and RT-qPCR. Plasma and hepatic metabolite levels were determined by HPLC. [Results] Expression ofmethionine cycle genesin themouse cochlea is age-regulated.No evidentimpactin hearing acuitywas observed by loss of Bhmt expression in youngmice.However,following noise challenge, knockout mice showed increased threshold shifts and poorerrecoverywith time, compared towild typemice. This enhanced susceptibility to noise damage associated with severe alterations in cochlear cytoarchitecture, altered expression of cochlear methionine cycle genes and hyperhomocysteinemia. [Conclusions] BHMT plays a central role in the homeostasis of cochlear methionine metabolism. Bhmt deficiency leads to an increased susceptibility to noise-induced hearing loss.Peer Reviewe