視覚野においてT型Ca²⁺チャネル依存性長期増強を引き起こすためにはTNFαが必要である

Monocular deprivation produces depression and potentiation of visual responses evoked in visual cortical neurons by stimulation of deprived and nondeprived eyes, respectively, during the critical period of ocular dominance plasticity. Our previous studies suggested that T-type Ca²⁺ channel-dependent long-term potentiation (LTP), induced by 2 Hz stimulation, mediates the potentiation of visual responses. However, it was proposed that the experience-dependent response potentiation is mediated by tumor necrosis factor-α (TNFα)-dependent homeostatic synaptic scaling but not by Hebbian synaptic plasticity, because the potentiation was absent in TNFα knockout (TNFα-KO) mice. In this study, we investigated whether TNFα is required for LTP induced by 2 Hz stimulation using visual cortical slices prepared from critical period mice and rats. The production of LTP was prevented by pharmacological blockade of TNFα in rats and mice. LTP production was also prevented by an inhibitor of TNFα-converting enzyme that converts membrane-bound TNFα to soluble TNFα. In TNFα-KO mice, LTP did not occur and was rescued by exogenous soluble TNFα. Soluble TNFα was required for LTP production only during a restricted time window soon after 2 Hz stimulation. These results strengthen the view that T-type Ca²⁺ channel-dependent LTP contributes to the potentiation of nondeprived eye responses following monocular deprivation.博士（医学）・乙第1401号・平成29年6月28日Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved

サリチル酸誘発耳鳴に対する牛車腎気丸の抑制効果の行動学的および免疫組織化学的な根拠

Many people are affected by tinnitus, a sensation of ringing in the ear despite the absence of external sound. Goshajinkigan (GJG) is one of the formulations of Japanese traditional herbal medicine and is prescribed for the palliative treatment of patients with tinnitus. Although GJG is clinically effective in these patients, its behavioral effects and the underlying neuroanatomical substrate have not been modeled in animals. We modeled tinnitus using salicylate-treated rats, demonstrated the effectiveness of GJG on tinnitus, and examined the underlying neuronal substrate with c-Fos expression. Intraperitoneal injection of sodium salicylate (400 mg/kg) into rats for three consecutive days significantly increased false positive scores, which were used to assess tinnitus behavior. When GJG was orally administered one hour after each salicylate injection, the increase in tinnitus behavior was suppressed. The analysis of c-Fos expression in auditory-related brain areas revealed that GJG significantly reduced the salicylate-induced increase in the number of c-Fos-expressing cells in the auditory cortices, inferior colliculus, and dorsal cochlear nucleus. These results suggest a suppressive effect of GJG on salicylate-induced tinnitus in animal models.博士（医学）・甲第851号・令和4年9月28日Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)