We demonstrated that activation of protein kinase Cδ (PKCδ) and inactivation of the glutathione peroxidase-1 (GPx-1)-dependent systems are critical for methamphetamine (MA)-induced recognition memory impairment. We also demonstrated that exposure to far-infrared rays (FIR) causes induction of the glutathione (GSH)-dependent system, including induction of the GPx-1 gene. Here, we investigated whether exposure to FIR rays affects MA-induced recognition memory impairment and whether it modulates PKC, cholinergic receptors, and the GSH-dependent system. Because the PKC activator bryostatin-1 mainly induces PKCα, PKCε, and PKCδ, we assessed expression of these proteins after MA treatment. MA treatment selectively increased PKCδ expression and its phosphorylation. Exposure to FIR rays significantly attenuated MA-induced increases in PKCδ phosphorylation. Importantly, bryostatin-1 potentiated MA-induced phosphorylation of PKCδ. MA treatment significantly decreased M1, M3, and M4 muscarinic acetylcholine receptors (mAChRs) and β2 nicotinic acetylcholine receptor expression. Of these, the decrease was most pronounced in M1 mAChR. Exposure to FIR significantly attenuated MA-induced decreases in the M1 mAChR and phospho-ERK_1/2, while it facilitated Nrf2-dependent GSH induction. Dicyclomine, an M1 mAChR antagonist, and L-buthionine-(S, R)-sulfoximine (BSO), an inhibitor of GSH synthesis, counteracted against the protective potentials mediated by FIR. More importantly, the memory-enhancing potential of FIR rays was significantly counteracted by bryostatin-1, dicyclomine, and BSO. Our results suggest that exposure to FIR rays attenuates MA-induced impairment in recognition memory via up-regulation of M1 mAChR, Nrf2-dependent GSH induction, and ERK_1/2 phosphorylation by inhibiting PKCδ phosphorylation by bryostatin-1.

我们证明了蛋白激酶Cδ（PKCδ）的激活和谷胱甘肽过氧化物酶1（GPx-1）依赖性系统的失活对于甲基苯丙胺（MA）诱导的识别记忆障碍至关重要。我们还证明了暴露于远红外线（FIR）会引起谷胱甘肽（GSH）依赖系统的诱导，包括GPx-1基因的诱导。在这里，我们调查了暴露于FIR射线是否会影响MA诱导的识别记忆障碍，以及它是否调节PKC，胆碱能受体和GSH依赖性系统。因为PKC激活剂bryostatin-1主要诱导PKCα，PKCε和PKCδ，所以我们评估了MA处理后这些蛋白的表达。MA处理选择性地增加了PKCδ的表达及其磷酸化。暴露于FIR射线会大大减弱MA诱导的PKCδ磷酸化的增加。重要的是，bryostatin-1增强了MA诱导的PKCδ磷酸化。MA治疗显着降低M1，M3和M4毒蕈碱型乙酰胆碱受体（mAChRs）和β2烟碱型乙酰胆碱受体表达。其中，下降最明显的是M1 mAChR。暴露于FIR显着减弱了MA诱导的M1 mAChR和磷酸化ERK的下降_1/2，而它促进Nrf2依赖的GSH诱导。M1 mAChR拮抗剂双环胺和GSH合成抑制剂L-丁硫氨酸-（S，R）-亚磺酰亚胺（BSO）抵消了FIR介导的保护电位。更重要的是，Bryostatin-1，双环胺和BSO明显抵消了FIR射线增强记忆的潜力。我们的结果表明通过M1的mAChR，Nrf2的依赖性GSH诱导，和ERK的上调，暴露于FIR射线衰减MA诱发的损伤在识别存储器_1/2由苔藓抑素-1抑制PKCδ磷酸化的磷酸化。