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首页> 外文期刊>The European Journal of Neuroscience >Long-term behavioural, molecular and morphological effects of neonatal NMDA receptor antagonism.
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Long-term behavioural, molecular and morphological effects of neonatal NMDA receptor antagonism.

机译:新生儿NMDA受体拮抗作用的长期行为,分子和形态学影响。

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摘要

Brief N-methyl-d-aspartate (NMDA) receptor blockade in neonatal rats has been reported to increase neuronal apoptosis. We replicated this finding using MK-801 (0.5 mg/kg) administered twice on postnatal day 7, and then studied the long-term consequences. In adulthood, treated rats showed reduced volume and neuronal number within the hippocampus, and altered hippocampal NMDA receptor (NR1 subunit) expression. Synaptophysin mRNA was decreased in the thalamus (laterodorsal nucleus). Adult MK-801-treated females had prepulse inhibition deficits and increased locomotor activity. The data show that a transient and limited glutamatergic intervention during development can have chronic behavioural, structural and molecular effects. The effects are reminiscent of alterations reported in schizophrenia and, as such, are consistent with hypotheses advocating a role for NMDA receptor hypofunction, and aberrant apoptosis, in the neurodevelopmental pathogenesis of the disorder.
机译:据报道,新生大鼠中短暂的N-甲基-d-天冬氨酸(NMDA)受体阻滞增加神经元凋亡。我们在出生后第7天使用两次MK-801(0.5 mg / kg)重复了这一发现,然后研究了长期后果。成年后,治疗的大鼠显示海马体积和神经元数量减少,海马NMDA受体(NR1亚基)表达改变。丘脑(横突核)的突触素mRNA减少。经MK-801治疗的成年女性具有前冲抑制功能缺陷和运动能力增强。数据显示,在发育过程中进行短暂且有限的谷氨酸能干预可能具有慢性行为,结构和分子效应。这种作用使人联想到精神分裂症中报道的改变,因此,与主张NMDA受体功能低下和异常细胞凋亡在该病的神经发育发病机制中起作用的假说一致。

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