AUTHOR=Camerino Claudia , Conte Elena , Carratù Maria Rosaria , Fonzino Adriano , Lograno Marcello Diego , Tricarico Domenico 

TITLE=Oxytocin/Osteocalcin/IL-6 and NGF/BDNF mRNA Levels in Response to Cold Stress Challenge in Mice: Possible Oxytonic Brain-Bone-Muscle-Interaction

JOURNAL=Frontiers in Physiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2019.01437

DOI=10.3389/fphys.2019.01437

ISSN=1664-042X

ABSTRACT=<p>Oxytocin (Oxt), osteocalcin (Ost), and NGF/BDNF have a role in bone homeostasis, reproduction, and cognition. Oxt/Ost is required for muscle repair. We investigated gene response of muscle and the inter-organ communication following cold stress (CS). The mRNA quantity of <italic>Ngf</italic>, <italic>Ost</italic>, <italic>Oxt</italic>, <italic>Bdnf</italic>, <italic>p75ntr</italic>, <italic>Ntrk1</italic>, <italic>Gprc6a</italic>, <italic>Oxtr</italic>, <italic>Ntrk2</italic>, <italic>UCP1</italic>, and <italic>Il-6</italic> genes in bone, brain, soleus (SOL), and <italic>tibialis anterior</italic> (TA) muscles from adult mice following CS were investigated. The myosin heavy-chain <italic>Mhc2b</italic>, <italic>Mhc1</italic>, <italic>Mhc2x</italic>, and <italic>Mhc2a</italic> gene expression were investigated. Mice were maintained at <italic>T</italic> = 23°C or 4°C for 6 h and 5-days (5d). CS mice did not show signs of muscle degeneration. An upregulation of <italic>Ucp1</italic> and <italic>Ngf</italic> genes by 2 and 1.5 folds, respectively, in TA after 6 h CS and <italic>Ntrk1</italic> by 4 and 22 folds in SOL muscle after 6 h and 5d CS, respectively, was observed; while after 6 h CS <italic>p75Ntr</italic> was downregulated in either muscle. <italic>Bdnf</italic> was unaffected, while after 5d CS <italic>Ntrk2</italic> was upregulated in TA. <italic>Ost</italic> was downregulated in SOL by 0.9-folds at 5d. Following 5d CS, <italic>Oxtr</italic> and <italic>Il-6</italic> genes were upregulated, respectively, by 1 and 1.5 folds in SOL. A downregulation of <italic>Mhc2b</italic>, respectively, by 0.96 and 0.88-folds after 6 h and 5d CS in SOL and <italic>Mhc2a</italic> was also downregulated by 0.88-fold after 5d CS in TA. <italic>Mhc1</italic> and <italic>Mhc2x</italic> were not affected. Changes in the expression levels of genes in TA and SOL muscles, bone, and brain following CS were regulated by IL6 and Oxt. CS potentiates the slow-twitch phenotype of SOL which is in line with the metabolic need of this muscle, and the potentiation of the slow-twitch phenotype in TA. Oxt and IL6 coordinate a phenotype-dependent tonic effect of slow-twitch muscle and Oxt regulates the inter-organ interaction between brain and SOL muscle. Muscle tropism is maintained by NGF signaling following CS.</p>