Shukla Pavan, Akotkar Likhit, Aswar Urmila
Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India.
Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India.
Neurosci Lett. 2024 Jan 18;820:137606. doi: 10.1016/j.neulet.2023.137606. Epub 2023 Dec 16.
Maternal deprivation (MD), a severe naturalistic type of stress in the early postnatal days, is a well-established model of early life stress (ELS) that models juvenile adversity and may result in significant depressive disease in adults. In order to analyze the behavioural, brain monoamine level and HPA axis dysregulations caused by ELS and to determine whether Resveratrol (Res) could counteract these effects, Wistar rat pups were subjected to the MD paradigm, which simulated the consequences of depression.
The pups on their postnatal day 1-10 were divided in 5 groups (n = 8); nondeprived (ND), maternally deprived (DC), standard fluoxetine (FLX) (5 mg/kg i.p), Res (20, 40 mg/kg i.p). Excluding the ND group, other pups were separated from dam for 3hr/day from day 1 to 10th day. Treatment was initiated from 50th day and was given for 12 days. The behaviour parameters light/dark test, sucrose preference, and resident intruder test were employed. Serum cortisol levels, brain antioxidant activity, monoamine levels and neuronal morphology in the hippocampus were assessed.
The MD rats showed altered behaviour, including more light-dark transitions, less desire for sucrose, and lower attack latencies. MD influenced the release of serum cortisol and interfered with monoamine, antioxidant levels as well as reduced Nissl bodies in the hippocampus. Treatment with Res led to improved behavioural functions also restored monoamine levels, reduced cortisol release, oxidative stress and prevented histopathological alterations in the rat hippocampus.
Res showed neuroprotective effects by improving the brain antioxidants and monoamine levels and HPA axis dysregulation and thus improves MD induced depression like behaviour in Wistar rats.
母婴分离（MD）是出生后早期一种严重的自然应激类型，是一种成熟的早期生活应激（ELS）模型，可模拟青少年逆境，并可能导致成年人患严重抑郁症。为了分析ELS引起的行为、脑单胺水平和下丘脑-垂体-肾上腺（HPA）轴失调，并确定白藜芦醇（Res）是否可以抵消这些影响，将Wistar大鼠幼崽置于MD范式下，该范式模拟了抑郁症的后果。
将出生后1-10天的幼崽分为5组（n = 8）；未分离组（ND）、母婴分离组（DC）、标准氟西汀组（FLX）（5 mg/kg腹腔注射）、Res组（20、40 mg/kg腹腔注射）。除ND组外，其他幼崽从第1天到第10天每天与母鼠分离3小时。从第50天开始治疗，持续12天。采用明暗试验、蔗糖偏好试验和定居者-入侵者试验等行为参数。评估血清皮质醇水平、脑抗氧化活性、单胺水平和海马神经元形态。
MD大鼠表现出行为改变，包括更多的明暗转换、对蔗糖的欲望降低和攻击潜伏期缩短。MD影响血清皮质醇的释放，干扰单胺、抗氧化剂水平，并减少海马中的尼氏体。Res治疗可改善行为功能，恢复单胺水平，减少皮质醇释放、氧化应激，并防止大鼠海马的组织病理学改变。
Res通过改善脑抗氧化剂和单胺水平以及HPA轴失调表现出神经保护作用，从而改善MD诱导的Wistar大鼠的抑郁样行为。
