{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:18:53Z","timestamp":1768504733476,"version":"3.49.0"},"posted":{"date-parts":[[2023,1,13]]},"group-title":"Neuroscience","reference-count":51,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,3,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Ketogenic diets are emerging as protective interventions in preclinical and clinical models of somatosensory nervous system disorders. Additionally, dysregulation of succinyl-CoA 3-oxoacid CoA-transferase 1 (SCOT, encoded by\n                  <jats:italic>Oxct1<\/jats:italic>\n                  ), the fate-committing enzyme in mitochondrial ketolysis, has recently been described in Friedreich\u2019s ataxia and amyotrophic lateral sclerosis. However, the contribution of ketone metabolism in the normal development and function of the somatosensory nervous system remains poorly characterized. We generated sensory neuron-specific, Advillin-Cre knockout of SCOT (Adv-KO-SCOT) mice and characterized the structure and function of their somatosensory system. We used histological techniques to assess sensory neuronal populations, myelination, and skin and spinal dorsal horn innervation. We also examined cutaneous and proprioceptive sensory behaviors with the von Frey test, radiant heat assay, rotarod, and grid-walk tests. Adv-KO-SCOT mice exhibited myelination deficits, altered morphology of putative A\u03b4 soma from the dorsal root ganglion, reduced cutaneous innervation, and abnormal innervation of the spinal dorsal horn compared to wildtype mice. Synapsin 1-Cre-driven knockout of\n                  <jats:italic>Oxct1<\/jats:italic>\n                  confirmed deficits in epidermal innervation following a loss of ketone oxidation. Loss of peripheral axonal ketolysis was further associated with proprioceptive deficits, yet Adv-KO-SCOT mice did not exhibit drastically altered cutaneous mechanical and thermal thresholds. Knockout of\n                  <jats:italic>Oxct1<\/jats:italic>\n                  in peripheral sensory neurons resulted in histological abnormalities and severe proprioceptive deficits in mice. We conclude that ketone metabolism is essential for the development of the somatosensory nervous system. These findings also suggest that decreased ketone oxidation in the somatosensory nervous system may explain the neurological symptoms of Friedreich\u2019s ataxia.\n                <\/jats:p>","DOI":"10.1101\/2023.01.11.523492","type":"posted-content","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T20:10:43Z","timestamp":1673640643000},"source":"Crossref","is-referenced-by-count":0,"title":["Ketolysis is Required for the Proper Development and Function of the Somatosensory Nervous System"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9943-4498","authenticated-orcid":false,"given":"Jonathan","family":"Enders","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jarrid","family":"Jack","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paige","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Lasnier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Taylor 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