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Hyperhomocysteinemia causes premature hearing loss in C57BL/6J mice

AutorMartínez-Vega, Raquel ; Varela-Moreiras, Gregorio; Partearroyo, Teresa; Pajares, María A. ; Varela-Nieto, Isabel
Fecha de publicación30-sep-2012
CitaciónIEB (2012)
Resumen[Introduction]: Alterations in plasma homocysteine (pHcy) levels and betaine homocysteine methyltransferase (BHMT) expression have been reported in genetic mouse models of human deafness. BHMT is one of the enzymes responsible for Hcy remethylation leading to methionine synthesis, its changes being one of the causes of increased pHcy levels and indirectly altering production of glutathione (2). Nutritional factors modulate Hcy metabolism, and hence we have studied the impact of a dietary-induced folic acid deficiency on the cochlear methionine metabolism and in hearing. [Material and Methods]: Hearing capacity from the control and folate deficient diet groups was assessed by ABR threshold analyses after 8 weeks of treatment. RT-PCR and western blot were used to determine the cochlear levels of methionine metabolism enzymes, whereas pHcy was determined by HPLC. Cochlear morphology was evaluated by hematoxylin-eosin staining and immunohistochemistry techniques. [Results]: The control group showed normal ABR thresholds (8 to 28 KHz, 27- 48 dB SPL) whereas the folate-deficient group presented moderate to severe hearing loss (8 to 28 KHz, 52-85 dB SPL). Folate deficiency caused hyperhomocysteinemia together with significant changes in protein and mRNA levels of enzymes involved in methionine metabolism and oxidative stress biomarkers. Control and folate-deficient mice showed normal cytoarchitecture and signs of severe sensorineural hearing loss, respectively. [Conclusions]: Folate deficiency causes alterations in the cochlear methionine cycle leading to an increase in pHcy levels, which is concomitant with molecular and cellular alterations in this organ and premature hearing loss in the C57BL/6J mouse.
DescripciónTrabajo presentado al 49th Workshop on Inner Ear Biology celebrada en Alemania del 30 de septiembre al 2 de octubre de 2012.
URIhttp://hdl.handle.net/10261/93293
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