Considering the ongoing demographic age-shift, the challenge posed by age-related hearing loss (ARHL) on health and wellbeing urgently needs to become a priority, even if it is only for the fact that ARHL has been recognized as the major preventable risk factor, or even cause, al cognitive decline and Alzheimer disease. Basic and translational research strategies aimed at reverting or delaying aging mechanisms and processes in the cochlea and central auditory pathway, hold the promise at efficiently tackling such health challenge. In our current project, we will test the hypothesis that electrical stimulation (ES) al the auditory cortex has a dual beneficial effect to treat or prevent ARHL. Firstly, through activation al descending corticofugal connections, the cochlear efferent pathway will be stimulated, which will result in trophic signals which will slow down cochlear aging and promote hearing preservation. Secondly, cortical ES will rebalance cortical activity, thus counteracting cross-modal imbalances resulting from limited auditory inputs in ARHL leading to maladaptive plasticity. The combination al peripheral and central effects al cortical ES will result in delaying or halting ARHL.
A novel, advantageous ES method, based on frequency interference of electric fields (TIEF), which allows for improved focused and controlled cortical stimulation. TIEF stimulation effects on the cochlear efferent system and possible mechanisms of otoprotection against ARHL will be explored functionally through a combination of auditory brainstem response evoked potentials (ABRs), to test recovery of auditory thresholds, and Optical Coherence Tomography, to test improvement of cochlear micromechanics and sensory hair cell survival. Effects of TIEF on auditory receptor cell aging will be tested through quantitative histology, to test for preservation of sensory hair cells, and a combination of immunocytochemistry and qPCR to test for markers of inflammation in aging (inflammaging), oxidative stress and phagocytic stress in search of mechanisms of delayed peripheral auditory aging mediated by cortical ES.
Besides determination of optimal TIEF stimulation settings in the animal model, we will test functionally using ABRs, cortical auditory and visual evoked potentials and prepulse inhibition, whether crossmodal cortical imbalances and sensory recalibrations resulting from maladaptive plasticity are reversed or limited alter cortical stimulation in ARHL, and the outcome in hearing preservation. A combination of immunocytochemistry and qPCR to detect markers of neurotransmission and plasticity in the brain cortex will allow to focus on central mechanisms of ES otoprotection with TIEF.
The proof of concept of TIEF protection in ARHL and its mechanisms, will open the possibility of a prototype oriented to the challenge of treating a growing problem with great impact on healthy aging.
Lab 4 – Neuroplasticidad Auditiva
Investigador principal del grupo
Dr. Miguel Ángel Merchán Cifuentes
Catedrático de Universidad
Producción Científica
José Maria Criado Gutierrez
Profesor Titular de Universidad
Antonio Javier de la Fuente Juan
Profesor Contratado Doctor
Orlando Jorge Castellano Benitez
Profesor Contratado doctor
Venezia Carmona Barrón
Estudiante de Doctorado
Ines Santos Gonzalez del Campo
Estudiante de Doctorado
Ignacio Plaza López
Clarkson, C.; López, D.E.; Merchán, M.A.2010. Long-term functional recovery in the rat auditory system after unilateral auditory cortex ablation Acta Oto-Laryngologica. 130-3, pp.326-332.
Clarkson, C.; Herrero-Turrión, M.J.; Merchán, M.A.2012. Cortical auditory deafferentation induces long-term plasticity in the inferior colliculus of adult rats: Microarray and qPCR analysis Frontiers in Neural Circuits. Oct 2012, pp.1-32.
Lamas, V.; Alvarado, J.C.; Carro, J.; Merchán, M.A.2013. Long-Term Evolution of Brainstem Electrical Evoked Responses to Sound after Restricted Ablation of the Auditory Cortex PLoS ONE. 8-9.
Lamas, V.; Arévalo, J.C.; Juiz, J.M.; Merchán, M.A.2015. Acoustic input and efferent activity regulate the expression of molecules involved in cochlear micromechanics Frontiers in Systems Neuroscience. 8-JAN.
Cajal and de Castro’s neurohistological methods. Ed by: Merchán, M.A; De Felipe, J; De Castro, F. 2016.Oxford University Press. ISBN:978-0-19-022159-1.
Lamas, V.; Juiz, J.M.; Merchán, M.A.2017. Ablation of the auditory cortex results in changes in the expression of neurotransmission-related mRNAs in the cochlea Hearing Research. 346, pp.71-80.
Pernia, M.; Estevez, S.; Poveda, C.; Plaza, I.; Carro, J.; Juiz, J.M.; Merchan, M.A.2017. c-Fos and Arc/Arg3.1 expression in auditory and visual cortices after hearing loss: Evidence of sensory crossmodal reorganization in adult rats Journal of Comparative Neurology. 525-12, pp.2677-2689
Marianny Pernía Rosales; Iván Díaz García; Ana Cecilia Colmenárez Raga; Casto Rivadulla Fernández; Javier Cudeiro Mazaira; Ignacio Plaza; Miguel A. Merchán. 2019. Cross-modal reaction of auditory and visual cortices after long-term bilateral hearing deprivation in the rat Brain Structure and Function. Springer. 225-1, pp.129-148.
Colmenárez-Raga, Ana Cecilia; Díaz, Iván; Pernia, Marianny; Pérez-González, David; Delgado-García, José M; Carro, Juan; Plaza, Ignacio; Merchán, Miguel A. 2019. Reversible functional changes evoked by anodal epidural direct current electrical stimulation of the rat auditory cortex Frontiers in Neuroscience. Frontiers. 13, pp.356-356.
Clara M Poveda; María L Valero; Marianny Pernia; Juan C Alvarado; David K Ryugo; Miguel A Merchán; Jose M Juiz. 2020. Expression and Localization of Kv1.1 and Kv3.1b Potassium Channels in the Cochlear Nucleus and Inferior Colliculus after Long-Term Auditory Deafferentation Brain Science. MDPI open access journal. 10-1, pp.35.
Díaz, I., Colmenárez-Raga, A. C., Pérez-González, D., Carmona, V. G., Plaza Lopez, I., and Merchán, M. A. (2021). Effects of Multisession Anodal Electrical Stimulation of the Auditory Cortex on Temporary Noise-Induced Hearing Loss in the Rat. Front. Neurosci. doi:10.3389/fnins.2021.642047.
