Morphological and functional changes in TRPM8‐expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice |
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| Authors: | Laura Almaraz Enol Artime Cruz Morenilla‐Palao Juana Gallar Félix Viana Jesús Merayo‐Lloves Carlos Belmonte |
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| Affiliation: | 1. Instituto de Neurociencias, Universidad Miguel Hernández‐CSIC, San Juan de Alicante, Spain;2. Instituto Universitario Fernández‐Vega, Universidad de Oviedo & Fundación de Investigación Oftalmológica, Oviedo, Spain |
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| Abstract: | 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. |
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| Keywords: | aging cold thermoreceptors dry eye pain tearing trigeminal ganglion RRID: AB_221569 RRID: AB_300798 RRID: AB_291637 RRID: AB_477272 RRID: AB_90725 RRID: AB_310180 RRID: AB_725807 RRID: AB_2313606 RRID: AB_2534095 RRID: AB_2576217 RRID: AB_142924 RRID: AB_142540 RRID: AB_2313921 |
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