title: Long-term omega-3 fatty acid supplementation prevents expression changes in cochlear homocysteine metabolism and ameliorates progressive hearing loss in C57BL/6J mice.
abstract: Omega-3 polyunsaturated fatty acids (PUFAs) are essential nutrients well known for their beneficial effects, among others on cognitive development and maintenance, inflammation and oxidative stress. Previous studies have shown an inverse association between high plasma levels of PUFAs and age-related hearing loss, and the relationship between low serum folate and elevated plasma homocysteine levels and hearing loss. Therefore, we used C57BL/6J mice and long-term omega-3 supplementation to evaluate the impact on hearing by analyzing their auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) thresholds. The omega-3 group showed significantly lower ABR hearing thresholds (~25 dB sound pressure level) and higher DPOAE amplitudes in mid-high frequencies when compared to the control group. These changes did not correlate with alterations between groups in plasma homocysteine or serum folate levels as measured by high-performance liquid chromatography and a microbiological method, respectively. Aging in the control group was associated with imbalanced cytokine expression toward increased proinflammatory cytokines as determined by quantitative reverse transcriptase polymerase chain reaction; these changes were prevented by omega-3 supplementation. Genes involved in homocysteine metabolism showed decreased expression during aging of control animals, and only alterations in Bhmt and Cbs were significantly prevented by omega-3 feeding. Western blotting showed that omega-3 supplementation precluded the CBS protein increase detected in 10-month-old controls but also produced an increase in BHMT protein levels. Altogether, the results obtained suggest a long-term protective role of omega-3 supplementation on cochlear metabolism and progression of hearing loss.
authors: Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Arturo Duperier 4, 28029, Madrid, Spain,; Unidad 761, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029, Madrid, Spain.
authors: Raquel
authors: R
authors: Martínez-Vega
authors: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU San Pablo, Boadilla del Monte, Madrid, Spain.
authors: Teresa
authors: T
authors: Partearroyo
authors: Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Arturo Duperier 4, 28029, Madrid, Spain.
authors: Néstor
authors: N
authors: Vallecillo
authors: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU San Pablo, Boadilla del Monte, Madrid, Spain.
authors: Gregorio
authors: G
authors: Varela-Moreiras
authors: Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Arturo Duperier 4, 28029, Madrid, Spain,; Instituto de Investigación Sanitaria La Paz (IdiPAZ), Paseo de la Castellana 261, 28046, Madrid, Spain. Electronic address: mapajares@iib.uam.es.
authors: María A
authors: MA
authors: Pajares
authors: Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Arturo Duperier 4, 28029, Madrid, Spain,; Unidad 761, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029, Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPAZ), Paseo de la Castellana 261, 28046, Madrid, Spain.
authors: Isabel
authors: I
authors: Varela-Nieto
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid; D003051:Cochlea / Q000378:metabolism*; D019587:Dietary Supplements; D016057:Evoked Potentials, Auditory, Brain Stem; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D005492:Folic Acid / Q000097:blood; D034381:Hearing Loss / Q000378:metabolism*; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D011312:Pressure; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D006710:Homocysteine; D005492:Folic Acid
keywords: Eicosapentaenoic acid; Homocysteine metabolism; Inflammation; Omega-3 fatty acids; Oxidative stress; Presbycusis