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哺乳期母鼠的硫胺素限制可导致其后代大脑中的谷氨酸和 GABA 浓度改变,并引起认知障碍。

Maternal thiamine restriction during lactation induces cognitive impairments and changes in glutamate and GABA concentrations in brain of rat offspring.

机构信息

Departamento de Bioquímica e Imunologia, Laboratório de Neurociência Comportamental e Molecular, LaNeC, Universidade Federal de Minas Gerais, Belo Horizonte 31270-010, Brazil.

出版信息

Behav Brain Res. 2010 Jul 29;211(1):33-40. doi: 10.1016/j.bbr.2010.03.002. Epub 2010 Mar 6.

DOI:10.1016/j.bbr.2010.03.002
PMID:20211656
Abstract

Maternal thiamine deficiency causes changes in cellular energy metabolism that can interfere with offspring brain development. The purpose of the present study was to investigate the effects of thiamine restriction, during lactation, on offspring neurochemistry and cognitive parameters. Male young (31 days old) and adult (75 days old) rats, from control and restricted mothers, were submitted to spatial learning and memory assessment. GABAergic and glutamatergic parameters were measured in thalamus, prefrontal cortex and hippocampus by high performance liquid chromatography (HPLC). The young animals were assessed immediately after thiamine restricted period; the adults, however, underwent a recovery period of 45 days. In young rats, thiamine restriction significantly hindered body weight gain and learning speed; however, it did not affect the brain weight, GABA and glutamate parameters in any of the brain assessed areas. In adult rats the body weight gain was significantly hampered by thiamine restriction, while brain weight and spatial task were not affected. Also, in adult offspring, maternal thiamine restriction significantly decreased the glutamate and GABA contents in the three assessed brain areas and thalamus, respectively. One possible explanation for these findings is that an adjustment of the inhibitory (GABAergic) and stimulatory (glutamatergic) neuromodulation systems occurs, in order to reverse the behavioral deficits detected in young rats but not in adult ones. The present data show, for the first time, that maternal thiamine restriction during lactation induces cognitive impairments and neurochemical changes in offspring, corroborating the important role of thiamine in brain development.

摘要

母体硫胺素缺乏会导致细胞能量代谢发生变化,从而干扰后代大脑发育。本研究旨在探讨哺乳期硫胺素限制对后代神经化学和认知参数的影响。雄性幼鼠(31 天大)和成年鼠(75 天大)分别来自对照组和限制组的母亲,接受空间学习和记忆评估。通过高效液相色谱法(HPLC)测量丘脑、前额叶皮层和海马中的 GABA 能和谷氨酸能参数。幼鼠在接受硫胺素限制后立即进行评估;而成年鼠则经历了 45 天的恢复期。在幼鼠中,硫胺素限制显著阻碍了体重增加和学习速度;然而,它并没有影响任何评估脑区的脑重、GABA 和谷氨酸参数。在成年大鼠中,硫胺素限制显著阻碍了体重增加,而脑重和空间任务不受影响。此外,在成年后代中,母体硫胺素限制显著降低了三个评估脑区和丘脑的谷氨酸和 GABA 含量。这些发现的一个可能解释是,为了逆转在幼鼠中检测到的行为缺陷,但在成年鼠中没有,抑制性(GABA 能)和兴奋性(谷氨酸能)神经调节系统发生了调整。本研究数据首次表明,哺乳期母体硫胺素限制会导致后代认知障碍和神经化学变化,证实了硫胺素在大脑发育中的重要作用。

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