Maternal chewing during prenatal stress ameliorates stress-induced hypomyelination, synaptic alterations, and learning impairment in mouse offspring

Maternal chewing during prenatal stress ameliorates stress-induced hypomyelination, synaptic alterations, and learning impairment in mouse offspring
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DOI:
10.1016/j.brainres.2016.09.007
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发表时间:
2016-11
期刊:
影响因子:
2.9
通讯作者:
Ayumi Suzuki;M. Iinuma;Sakurako Hayashi;Yuichi Sato;K. Azuma;K. Kubo
Ayumi Suzuki;M. Iinuma;Sakurako Hayashi;Yuichi Sato;K. Azuma;K. Kubo
中科院分区:
医学3区
文献类型:
--
作者:
Ayumi Suzuki;M. Iinuma;Sakurako Hayashi;Yuichi Sato;K. Azuma;K. Kubo

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孕期应激期间的母体咀嚼可以减轻应激诱导的学习缺陷的发展,并减少小鼠海马齿状回细胞增殖。海马髓鞘形成影响空间记忆,突触结构是神经元通讯的重要中介。我们调查了孕期应激期间母体咀嚼是否能改善应激诱导的海马髓鞘和突触的改变,以及成年后代空间记忆发育受损的情况。将怀孕小鼠分为对照组、应激组和应激/咀嚼组。应激是通过将小鼠置于通风束缚管中来诱导的,从怀孕第12天开始并持续到分娩。应激/咀嚼组的小鼠在束缚期间被给予一根木棍咀嚼。1月龄幼鼠在Morris水迷宫中进行空间记忆测试,并用免疫组织化学和电子显微镜观察CA1区少突胶质细胞和突触的变化。孕期应激可导致成年仔鼠学习能力下降,并降低成年子代海马CA1区髓鞘碱性蛋白(MBP)和2‘,3’-环核苷酸3‘-磷酸二酯酶(CNPase)的免疫活性。可见大量髓鞘异常。海马CA1区[轴突直径与轴突纤维直径之比(轴突加髓鞘)]增大,突触后密度长度减小。母鼠应激期间的咀嚼可减轻孕期应激所致的空间记忆障碍,并可使大鼠海马CA1区MBP和CNPase免疫反应性降低,G比率增加,突触后密度长度缩短。这些发现表明,在母鼠出生前应激期间咀嚼食物可能是一种有效的应对策略,可以防止其后代的海马体行为和形态损伤。
Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring.