Acyl-Ghrelin Attenuates Neurochemical and Motor Deficits in the 6-OHDA Model of Parkinson's Disease.

Acyl-Ghrelin Attenuates Neurochemical and Motor Deficits in the 6-OHDA Model of Parkinson's Disease.
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DOI:
10.1007/s10571-022-01282-9
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发表时间:
2023-07
影响因子:
4
通讯作者:
--
中科院分区:
医学3区
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--
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在实验性帕金森病(PD)小鼠1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)模型中,摄食相关激素酰基-ghrelin可保护多巴胺神经元。然而,在更广泛使用的6-羟基多巴胺(6-OHDA)大鼠内侧前脑束(MFB)损伤模型中,酰基-ghrelin对黑质丘脑部(SNpc)多巴胺能神经元的潜在保护作用以及随后的行为相关性尚不清楚。为了解决这个问题,酰基-生长激素释放肽水平直接提高了7天,然后单侧注射6-OHDA到MFB与苯丙胺诱导的旋转的第27和35天的评估,多巴胺能神经元的存活的免疫组织化学分析。虽然酰基-ghrelin治疗不足以提高食物摄入量或体重,但它减弱了安非他明诱导的盘旋行为和6-OHDA诱导的SNpc多巴胺神经元丢失。这些数据支持这样的观点,即升高循环酰基-生长激素释放肽可能是减缓或削弱PD中神经元损失进展的有价值的方法。
The feeding-related hormone, acyl-ghrelin, protects dopamine neurones in murine 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-based models of experimental Parkinson’s disease (PD). However, the potential protective effect of acyl-ghrelin on substantia nigra pars compacta (SNpc) dopaminergic neurones and consequent behavioural correlates in the more widely used 6-hydroxydopamine (6-OHDA) rat medial forebrain bundle (MFB) lesion model of PD are unknown. To address this question, acyl-ghrelin levels were raised directly by mini-pump infusion for 7 days prior to unilateral injection of 6-OHDA into the MFB with assessment of amphetamine-induced rotations on days 27 and 35, and immunohistochemical analysis of dopaminergic neurone survival. Whilst acyl-ghrelin treatment was insufficient to elevate food intake or body weight, it attenuated amphetamine-induced circling behaviour and SNpc dopamine neurone loss induced by 6-OHDA. These data support the notion that elevating circulating acyl-ghrelin may be a valuable approach to slow or impair progression of neurone loss in PD.
酰化 Ghrelin 通过调节自噬通量来预防 6-OHDA 诱导的神经毒性
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