关键词: anxiety brain development melatonin memory redox imbalance spreading depression

来  源:   DOI:10.3389/fnins.2023.1269609   PDF(Pubmed)

Abstract:
UNASSIGNED: Melatonin (MLT) reportedly has beneficial effects in neurological disorders involving brain excitability (e.g., Epilepsy and Migraine) and behavioral patterns (e.g., Anxiety and Depression). This study was performed to investigate, in the developing rat brain, the effect of early-in-life administration of two different doses of exogenous MLT on behavioral (anxiety and memory) and electrophysiological (CSD analysis) aspects of brain function. Additionally, brain levels of malondialdehyde (MDA) and superoxide dismutase (SOD), both cellular indicators of redox balance status, were evaluated. We hypothesize that MLT differentially affects the behavioral and CSD parameters as a function of the MLT dose.
UNASSIGNED: Male Wistar rats received, from the 7th to the 27th postnatal day (PND), on alternate days, vehicle solution, or 10 mg/kg/or 40 mg/kg MLT (MLT-10 and MLT-40 groups), or no treatment (intact group). To perform behavioral and cognition analysis, from PND30 to PND32, they were tested in the open field apparatus, first for anxiety (PND30) and then for object recognition memory tasks: spatial position recognition (PND31) and shape recognition (PND32). On PND34, they were tested in the elevated plus maze. From PND36 to 42, the excitability-related phenomenon known as cortical spreading depression (CSD) was recorded, and its features were analyzed.
UNASSIGNED: Treatment with MLT did not change the animals\' body weight or blood glucose levels. The MLT-10 treatment, but not the MLT-40 treatment, was associated with behaviors that suggest less anxiety and improved memory. MLT-10 and MLT-40 treatments, respectively, decelerated and accelerated CSD propagation (speed of 2.86 ± 0.14 mm/min and 3.96 ± 0.16 mm/min), compared with the control groups (3.3 ± 0.10 mm/min and 3.25 ± 0.11 mm/min, for the intact and vehicle groups, respectively; p < 0.01). Cerebral cortex levels of malondialdehyde and superoxide dismutase were, respectively, lower and higher in the MLT-10 group but not in the MLT40 group.
UNASSIGNED: Our findings suggest that MLT intraperitoneal administration during brain development may differentially act as an antioxidant agent when administered at a low dose but not at a high dose, according to behavioral, electrophysiological, and biochemical parameters.
摘要:
据报道,褪黑激素(MLT)对涉及大脑兴奋性的神经系统疾病具有有益作用(例如,癫痫和偏头痛)和行为模式(例如,焦虑和抑郁)。这项研究是为了调查,在发育中的大鼠大脑中,生命早期给予两种不同剂量的外源性MLT对脑功能的行为(焦虑和记忆)和电生理(CSD分析)方面的影响。此外,丙二醛(MDA)和超氧化物歧化酶(SOD),氧化还原平衡状态的两种细胞指标,进行了评估。我们假设MLT不同地影响作为MLT剂量的函数的行为和CSD参数。
雄性Wistar大鼠,从产后第7天到第27天(PND),隔天,车辆解决方案,或10mg/kg/或40mg/kgMLT(MLT-10和MLT-40组),或不治疗(完整组)。进行行为和认知分析,从PND30到PND32,它们在开放式现场设备中进行了测试,首先是焦虑(PND30),然后是对象识别记忆任务:空间位置识别(PND31)和形状识别(PND32)。在PND34上,他们在高架迷宫中进行了测试。从PND36到42,记录了被称为皮质扩散抑制(CSD)的兴奋性相关现象,并对其特点进行了分析。
用MLT处理没有改变动物的体重或血糖水平。MLT-10治疗,但不是MLT-40治疗,与表明焦虑减少和记忆改善的行为有关。MLT-10和MLT-40治疗,分别,减速和加速CSD传播(速度为2.86±0.14mm/min和3.96±0.16mm/min),与对照组(3.3±0.10mm/min和3.25±0.11mm/min,对于完整的和车辆组,分别为;p<0.01)。大脑皮层丙二醛和超氧化物歧化酶的水平,分别,在MLT-10组中较低和较高,但在MLT40组中没有。
我们的发现表明,在大脑发育过程中,MLT腹膜内给药可能在低剂量而不是高剂量给药时具有不同的抗氧化剂作用,根据行为,电生理学,和生化参数。
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