■暴露于Δ9-四氢大麻酚(THC)是确定的晚年神经精神脆弱性的危险因素,包括情绪和焦虑相关症状。已知THC对情感和焦虑行为现象的精神作用针对纹状体网络,尤其是伏隔核,与情绪和焦虑症病理生理学相关的神经区域。THC可能通过氧化还原系统增加神经炎症反应,并在各种脑回路中失调抑制性和兴奋性神经平衡,包括纹状体.因此,可以诱导抗氧化作用的干预措施可能抵消THC暴露对神经发育的影响.
■在当前的研究中,我们使用建立的临床前青春期大鼠模型来检查青春期THC暴露对各种行为的影响,分子,以及与情绪和焦虑症易感性增加相关的神经元生物标志物。此外,我们研究了抗氧化剂N-乙酰半胱氨酸对THC相关病理的保护特性。
■我们证明,青少年THC暴露可引起持久的焦虑和抑郁样表型,并伴有伏隔核两个亚区的神经元和分子异常,外壳和核心。此外,我们首次报道N-乙酰半胱氨酸可以预防THC诱导的伏隔病理生理和相关行为异常。
■这种抗氧化剂干预的预防作用突出了大麻素诱导的神经发育病理基础的氧化还原机制的关键作用,并确定了预防和/或逆转这些病理生理后遗症的潜在干预策略。
青春期持续使用大麻会增加神经精神疾病的易感性,包括焦虑和抑郁.使这些病理结果正常化的药物治疗干预措施仍然有限。我们对青少年暴露于Δ9-四氢大麻酚(THC)的影响进行了全面和综合的翻译分析,大麻中的主要精神活性成分。此外,我们测试了抗氧化剂N-乙酰半胱氨酸(NAC)的保护性能。THC治疗的大鼠表现出焦虑和抑郁样表型,并伴有伏隔核的神经元和分子失调,情绪障碍的关键领域。NAC阻止了THC相关病理的发展。这些发现确定了预防大麻暴露引起的神经发育障碍的潜在策略。
UNASSIGNED: Exposure to Δ9-tetrahydrocannabinol (THC) is an established risk factor for later-life neuropsychiatric vulnerability, including mood- and anxiety-related symptoms. The psychotropic effects of THC on affect and anxiogenic behavioral phenomena are known to target the striatal network, particularly the nucleus
accumbens, a neural region linked to mood and anxiety disorder pathophysiology. THC may increase neuroinflammatory responses via the redox system and dysregulate inhibitory and excitatory neural balance in various brain circuits, including the striatum. Thus, interventions that can induce antioxidant effects may counteract the neurodevelopmental impacts of THC exposure.
UNASSIGNED: In the current study, we used an established preclinical adolescent rat model to examine the impacts of adolescent THC exposure on various behavioral, molecular, and neuronal biomarkers associated with increased mood and anxiety disorder vulnerability. Moreover, we investigated the protective properties of the antioxidant N-acetylcysteine against THC-related pathology.
UNASSIGNED: We demonstrated that adolescent THC exposure induced long-lasting anxiety- and depressive-like phenotypes concomitant with differential neuronal and molecular abnormalities in the two subregions of the nucleus
accumbens, the shell and the core. In addition, we report for the first time that N-acetylcysteine can prevent THC-induced accumbal pathophysiology and associated behavioral abnormalities.
UNASSIGNED: The preventive effects of this antioxidant intervention highlight the critical role of redox mechanisms underlying cannabinoid-induced neurodevelopmental pathology and identify a potential intervention strategy for the prevention and/or reversal of these pathophysiological sequelae.
Sustained cannabis use during adolescence increases vulnerability to neuropsychiatric disorders, including anxiety and depression. Pharmacotherapeutic interventions to normalize these pathological outcomes are still limited. We performed a comprehensive and integrative translational analysis of the effects of adolescent exposure to Δ9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis. Moreover, we tested the protective properties of the antioxidant N-acetylcysteine (NAC). THC-treated rats exhibited anxiety and depressive-like phenotypes concomitant with neuronal and molecular dysregulations in the nucleus
accumbens, a crucial area for mood disorders. NAC prevented the development of THC-related pathology. These findings identified a potential strategy to prevent the neurodevelopmental disorders induced by cannabis exposure.