Impaired spatial memory in adult vitamin D deficient BALB/c mice is associated with reductions in spine density, nitric oxide, and neural nitric oxide synthase in the hippocampus.
Impaired spatial memory in adult vitamin D deficient BALB/c mice is associated with reductions in spine density, nitric oxide, and neural nitric oxide synthase in the hippocampus.
复制标题
DOI：
10.3934/neuroscience.2022004
复制
发表时间：
2022
影响因子：
2.7
通讯作者：
Burne THJ
中科院分区：
文献类型：
--
作者：
Al-Amin MM;Sullivan RKP;Alexander S;Carter DA;Bradford D;Burne THJ
维生素D缺乏症在成年人中普遍存在，并与认知障碍有关。然而，成人维生素D（AVD）缺乏影响认知功能的机制仍不清楚。我们研究了AVD缺陷的BALB/c小鼠的空间记忆障碍及其潜在的机制，通过测量脊髓密度，长时程增强（LTP），一氧化氮（NO），神经元型一氧化氮合酶（nNOS），和内皮型NOS（eNOS）在海马。成年雄性BALB/c小鼠喂食对照或维生素D缺乏饮食20周。空间记忆的表现进行了测量，使用主动回避（阿帕）任务，其中AVD缺陷小鼠减少了潜伏期进入休克区相比，控制。我们在CA 1和齿状回（DG）中表征了海马棘形态，并在行为幼稚小鼠的海马中进行了电生理记录以测量LTP。接下来，我们测量了NO，以及谷胱甘肽，脂质过氧化和蛋白质产物的氧化，并定量海马nNOS和eNOS的免疫反应性。棘形态学分析显示，在CA 1树突，但不是在DG的蘑菇刺的数量显着减少。饮食对LTP没有影响。然而，海马NO水平被耗尽，而其他氧化标记物未被AVD缺陷改变。我们还显示了减少nNOS，但不是eNOS，免疫反应性。最后，对AVD缺陷小鼠补充维生素D 10周使nNOS免疫反应性恢复到对照小鼠中所见的水平。我们的研究结果表明，较低水平的NO和减少nNOS免疫染色有助于AVD缺陷小鼠的海马依赖性空间学习缺陷。
Vitamin D deficiency is prevalent in adults and is associated with cognitive impairment. However, the mechanism by which adult vitamin D (AVD) deficiency affects cognitive function remains unclear. We examined spatial memory impairment in AVD-deficient BALB/c mice and its underlying mechanism by measuring spine density, long term potentiation (LTP), nitric oxide (NO), neuronal nitric oxide synthase (nNOS), and endothelial NOS (eNOS) in the hippocampus. Adult male BALB/c mice were fed a control or vitamin D deficient diet for 20 weeks. Spatial memory performance was measured using an active place avoidance (APA) task, where AVD-deficient mice had reduced latency entering the shock zone compared to controls. We characterised hippocampal spine morphology in the CA1 and dentate gyrus (DG) and made electrophysiological recordings in the hippocampus of behaviourally naïve mice to measure LTP. We next measured NO, as well as glutathione, lipid peroxidation and oxidation of protein products and quantified hippocampal immunoreactivity for nNOS and eNOS. Spine morphology analysis revealed a significant reduction in the number of mushroom spines in the CA1 dendrites but not in the DG. There was no effect of diet on LTP. However, hippocampal NO levels were depleted whereas other oxidation markers were unaltered by AVD deficiency. We also showed a reduced nNOS, but not eNOS, immunoreactivity. Finally, vitamin D supplementation for 10 weeks to AVD-deficient mice restored nNOS immunoreactivity to that seen in in control mice. Our results suggest that lower levels of NO and reduced nNOS immunostaining contribute to hippocampal-dependent spatial learning deficits in AVD-deficient mice.