酒精使用障碍(Alcohol Use Disorder,AUD)是一种慢性、复发性脑疾病,目前尚缺乏有效治疗手段。近年来深部脑刺激(Deep Brain Stimulation,DBS)在AUD中有了不少探索性应用。尽管DBS在治疗酒精使用障碍方面才刚刚起步,仍处于研究阶段,但...酒精使用障碍(Alcohol Use Disorder,AUD)是一种慢性、复发性脑疾病,目前尚缺乏有效治疗手段。近年来深部脑刺激(Deep Brain Stimulation,DBS)在AUD中有了不少探索性应用。尽管DBS在治疗酒精使用障碍方面才刚刚起步,仍处于研究阶段,但颇有前景,有望成为治疗AUD的新手段之一。本文从DBS治疗AUD的潜在疗效、不良反应、作用机制等方面进行总结。展开更多
Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic ...Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.展开更多
Addiction has been extensively studied on many levels:from the molecular level,with various“omics”approaches(Natividad et al.,2018;Grecco et al.,2021),to the clinical level,with psychotherapy and MRI imaging(Ceceli ...Addiction has been extensively studied on many levels:from the molecular level,with various“omics”approaches(Natividad et al.,2018;Grecco et al.,2021),to the clinical level,with psychotherapy and MRI imaging(Ceceli et al.,2022).展开更多
文摘酒精使用障碍(Alcohol Use Disorder,AUD)是一种慢性、复发性脑疾病,目前尚缺乏有效治疗手段。近年来深部脑刺激(Deep Brain Stimulation,DBS)在AUD中有了不少探索性应用。尽管DBS在治疗酒精使用障碍方面才刚刚起步,仍处于研究阶段,但颇有前景,有望成为治疗AUD的新手段之一。本文从DBS治疗AUD的潜在疗效、不良反应、作用机制等方面进行总结。
基金supported by the National Natural Science Foundation of China,No.81971246 (to TM)Opening Foundation of Jiangsu Key Laboratory of Neurodegeneration,Nanjing Medical University,No.KF202204 (to LZ and SF)。
文摘Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.
文摘Addiction has been extensively studied on many levels:from the molecular level,with various“omics”approaches(Natividad et al.,2018;Grecco et al.,2021),to the clinical level,with psychotherapy and MRI imaging(Ceceli et al.,2022).
