Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice
| Autor: | Ignacio Alcalde, Laura Almaraz, Félix Viana, Almudena Íñigo-Portugués, Juana Gallar, Jesus Merayo-Lloves, Cruz Morenilla-Palao, Enol Artime, Omar González-González, Carlos Belmonte |
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| Přispěvatelé: | Ministerio de Economía, Industria y Competitividad (España), Ministerio de Ciencia e Innovación (España), Principado de Asturias, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación Ramón Areces, Caja Rural de Asturias, Departamentos de la UMH::Fisiología |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male trigeminal ganglion Aging TRPM Cation Channels Dry eye Pain Sensory system Biology Somatosensory system Fisiología Cornea 03 medical and health sciences Basal (phylogenetics) Trigeminal ganglion Mice dry eye 0302 clinical medicine TRPM8 medicine Animals pain Cold thermoreceptors tearing Nerve Endings Neurons Osmotic concentration General Neuroscience Osmolar Concentration aging Thermoreceptors Epithelium Cell biology 030104 developmental biology medicine.anatomical_structure cold thermoreceptors Cryotherapy Tearing Tears Thermoreceptor Dry Eye Syndromes sense organs 030217 neurology & neurosurgery |
| Zdroj: | RUO. Repositorio Institucional de la Universidad de Oviedo instname REDIUMH. Depósito Digital de la UMH |
| ISSN: | 2013-0317 |
| Popis: | This is an open access article under the terms of the Creative Commons Attribution-Non Commercial-No Derivs License. Morphological and functional alterations of peripheral somatosensory neurons during the aging process lead to a decline of somatosensory perception. Here, we analyze the changes occurring with aging in trigeminal ganglion (TG), TRPM8-expressing cold thermoreceptor neurons innervating the mouse cornea, which participate in the regulation of basal tearing and blinking and have been implicated in the pathogenesis of dry eye disease (DED). TG cell bodies and axonal branches were examined in a mouse line (TRPM8BAC-EYFP) expressing a fluorescent reporter. In 3 months old animals, about 50% of TG cold thermoreceptor neurons were intensely fluorescent, likely providing strongly fluorescent axons and complex corneal nerve terminals with ongoing activity at 34°C and low-threshold, robust responses to cooling. The remaining TRPM8+ corneal axons were weakly fluorescent with nonbeaded axons, sparsely ramified nerve terminals, and exhibited a low-firing rate at 34°C, responding moderately to cooling pulses as do weakly fluorescent TG neurons. In aged (24 months) mice, the number of weakly fluorescent TG neurons was strikingly high while the morphology of TRPM8+ corneal axons changed drastically; 89% were weakly fluorescent, unbranched, and often ending in the basal epithelium. Functionally, 72.5% of aged cold terminals responded as those of young animals, but 27.5% exhibited very low-background activity and abnormal responsiveness to cooling pulses. These morpho-functional changes develop in parallel with an enhancement of tear's basal flow and osmolarity, suggesting that the aberrant sensory inflow to the brain from impaired peripheral cold thermoreceptors contributes to age-induced abnormal tearing and to the high incidence of DED in elderly people. This work was supported by grants FC-15-GRUPIN14–141 (Consejería de Economía y Empleo, Asturias, Spain), Fundación Ramón Areces, Caja Rural de Asturias, SAF2014–54518-C3-2-R, SAF2014–54518-C3-1-R, SAF2017–83674-C2-2-R, SAF2017–83674-C2-1-R, and SAF2016–77233-R (Ministerio de Economía, Industria y Competitividad, Spain and European Regional Development Funds, European Union), and “Severo Ochoa” Program for Centers of Excellence in R&D (SEV-2013-0317). |
| Databáze: | OpenAIRE |
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