Rapamycin Accelerates Axon Regeneration Through Schwann Cell-mediated Autophagy Following Inferior Alveolar Nerve Transection in Rats. (1st August 2021)

• Record Type: Journal Article
• Authors: Inada, Takanobu; Sato, Hitoshi; Hayashi, Yoshinori; Hitomi, Suzuro; Furukawa, Akihiko; Ando, Masatoshi; Oshima, Eri; Otsuji, Jo; Taguchi, Naoto; Shibuta, Ikuko; Tsuda, Hiromasa; Iwata, Koichi; Shirota, Tatsuo; Shinoda, Masamichi
• Is Part Of: Neuroscience. Volume 468(2021)
• Page Start: 43
• Page End: 52
• Publication Date: 2021-08-01
• Subjects: 3-MA 3-Methyladenine -- BDNF brain derived neurotrophic factor -- BDNF brain-derived neurotrophic factor -- FG Fluoro-Gold -- GDNF glial cell line-derived neurotrophic factor -- HRP horse radish peroxidase -- HWT head-withdrawal threshold -- IAN inferior alveolar nerve -- IANX inferior alveolar nerve transection -- IGF insulin-like growth factor -- IgG immunoglobulin G -- LC3 microtubule-associated protein-1 light chain 3 -- MBP myelin basic protein -- MPZ myelin protein zero -- mTOR mammalian target of rapamycin -- NGF nerve growth factor -- NGS normal goat serum -- PBS phosphate-buffered saline -- STAT3 signal transducer and activator of transcription 3 -- TBS-T Tween 20 -- TG trigeminal ganglion; rapamycin -- autophagy -- Schwann cell -- peripheral nerve transection -- axon regeneration; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2021.05.033
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Rapamycin facilitates autophagic activity in the transected inferior alveolar nerve. Rapamycin decreases the accumulation of myelin debris attributable to inferior alveolar nerve transection. Rapamycin promotes axon regeneration of the transected inferior alveolar nerve. Abstract: Sensory disturbance in the orofacial region owing to trigeminal nerve injury is caused by dental treatment or accident. Commercially available therapeutics are ineffective for the treatment of sensory disturbance. Additionally, the therapeutic effects of rapamycin, an allosteric inhibitor of mammalian target of rapamycin (mTOR), which negatively regulates autophagy, on the sensory disturbance are not fully investigated. Thus, we investigated the therapeutic effects of rapamycin on the sensory disturbance in the mandibular region caused by inferior alveolar nerve (IAN) transection (IANX) in rats. The expression levels of the phosphorylated p70S6K, a downstream molecule of mTOR, in the proximal and distal stumps of the transected IAN were significantly reduced by rapamycin administration to the injured site. Conversely, the increments of both Beclin 1 and microtubule-associated protein-1 light chain 3-II protein levels in the proximal and distal stumps of the transected IAN was induced by rapamycin administration. Immunohistochemical analyses revealed that Beclin 1 was located in Schwann cells in the proximal stump of the IAN. Accumulation of myelin protein zero and myelin basic protein in the proximal and distal stumps of the IAN was significantly reduced by rapamycin administration. Rapamycin administration facilitated axon regeneration after IANX and increased the number of brain-derived neurotrophic factor positive neurons in the trigeminal ganglion. Thus, recovery from sensory disturbance in the lower lip caused by IANX was markedly facilitated by rapamycin. These findings suggest that rapamycin administration is a promising treatment for the sensory disturbance caused by IANX.