Morphological and functional changes in TRPM8‐expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice. Issue 11 (2nd May 2018)

• Record Type: Journal Article
• Authors: Alcalde, Ignacio; Íñigo‐Portugués, Almudena; González‐González, Omar; Almaraz, Laura; Artime, Enol; Morenilla‐Palao, Cruz; Gallar, Juana; Viana, Félix; Merayo‐Lloves, Jesús; Belmonte, Carlos
• Is Part Of: Journal of comparative neurology. Volume 526:Issue 11(2018)
• Page Start: 1859
• Page End: 1874
• Publication Date: 2018-05-02
• Subjects: 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; Comparative neurobiology -- Periodicals; Neurology -- Periodicals; 616
• DOI: 10.1002/cne.24454
• Languages: English
• ISSNs: 0021-9967

Abstract

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 (TRPM8 BAC ‐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. Abstract : Old mice exhibit a majority of low fluorescence, poorly branched TRPM8‐GFP corneal axons and a very few highly fluorescence, richly branched TRPM8+ axons in contrast with young animals. Their cold‐sensitive terminals often display abnormal background activity and altered cold responsiveness. The abundance of low‐fluorescence cold corneal axons in old mice goes in parallel with a prominent increase in basal tearing rate, suggesting a causal relationship between abnormal cold thermoreceptor activity and tearing disturbances.