Allopregnanolone: The missing link to explain the effects of stress on tic exacerbation?,Journal of Neuroendocrinology

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Allopregnanolone: The missing link to explain the effects of stress on tic exacerbation?
Journal of Neuroendocrinology ( IF 3.3 ) Pub Date : 2021-07-30 , DOI: 10.1111/jne.13022
Marco Bortolato _{1,

2} , Barbara J Coffey _{2,

3} , Vilma Gabbay _{2,

4} , Simona Scheggi ₅

Affiliation

The neurosteroid allopregnanolone (3α-hydroxy-5α-pregnan-20-one; AP) elicits pleiotropic effects in the central nervous system, ranging from neuroprotective and anti-inflammatory functions to the regulation of mood and emotional responses. Several lines of research show that the brain rapidly produces AP in response to acute stress to reduce the allostatic load and enhance coping. These effects not only are likely mediated by GABA_A receptor activation but also result from the contributions of other mechanisms, such as the stimulation of membrane progesterone receptors. In keeping with this evidence, AP has been shown to exert rapid, potent antidepressant properties and has been recently approved for the therapy of moderate-to-severe postpartum depression. In addition to depression, emerging evidence points to the potential of AP as a therapy for other neuropsychiatric disorders, including anxiety, seizures, post-traumatic stress disorder and cognitive problems. Although this evidence has spurred interest in further therapeutic applications of AP, some investigations suggest that this neurosteroid may also be associated with adverse events in specific disorders. For example, our group has recently documented that AP increases tic-like manifestations in several animal models of tic disorders; furthermore, our results indicate that inhibiting AP synthesis and signalling reduces the exacerbation of tic severity associated with acute stress. Although the specific mechanisms of these effects remain partially elusive, our findings point to the possibility that the GABAergic activation by AP may also lead to disinhibitory effects, which could interfere with the ability of patients to suppress their tics. Future studies will be necessary to verify whether these mechanisms may apply to other externalising manifestations, such as impulse-control problems and manic symptoms.

中文翻译：

Allopregnanolone：解释压力对抽动恶化影响的缺失环节？

神经类固醇 allopregnanolone (3α-hydroxy-5α-pregnan-20-one; AP) 在中枢神经系统中引起多效性作用，从神经保护和抗炎功能到情绪和情绪反应的调节。几项研究表明，大脑在应对急性压力时会迅速产生 AP，以减少压力负荷并增强应对能力。这些影响不仅可能由 GABA _A介导受体激活也是由其他机制的贡献引起的，例如膜孕酮受体的刺激。与这一证据一致，AP 已被证明具有快速、有效的抗抑郁特性，并且最近已被批准用于治疗中度至重度产后抑郁症。除抑郁症外，新出现的证据表明 AP 作为治疗其他神经精神疾病的潜力，包括焦虑、癫痫发作、创伤后应激障碍和认知问题。尽管这一证据激发了人们对 AP 进一步治疗应用的兴趣，但一些研究表明，这种神经类固醇也可能与特定疾病的不良事件有关。例如，我们小组最近记录了 AP 增加了几种抽动障碍动物模型中的抽动样表现；此外，我们的结果表明，抑制 AP 合成和信号传导可降低与急性压力相关的抽动严重程度的恶化。尽管这些影响的具体机制仍然部分难以捉摸，但我们的研究结果表明，AP 的 GABA 能激活也可能导致去抑制作用，这可能会干扰患者抑制抽动的能力。未来的研究将有必要验证这些机制是否适用于其他外化表现，例如冲动控制问题和躁狂症状。我们的结果表明，抑制 AP 合成和信号传导可降低与急性压力相关的抽动严重程度的恶化。尽管这些影响的具体机制仍然部分难以捉摸，但我们的研究结果表明，AP 的 GABA 能激活也可能导致去抑制作用，这可能会干扰患者抑制抽动的能力。未来的研究将有必要验证这些机制是否适用于其他外化表现，例如冲动控制问题和躁狂症状。我们的结果表明，抑制 AP 合成和信号传导可降低与急性压力相关的抽动严重程度的恶化。尽管这些影响的具体机制仍然部分难以捉摸，但我们的研究结果表明，AP 的 GABA 能激活也可能导致去抑制作用，这可能会干扰患者抑制抽动的能力。未来的研究将有必要验证这些机制是否适用于其他外化表现，例如冲动控制问题和躁狂症状。

更新日期：2021-07-30

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