Long-term behavioural, molecular and morphological effects of neonatal NMDA receptor antagonism
Long-term behavioural, molecular and morphological effects of neonatal NMDA receptor antagonism
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DOI：
10.1046/j.1460-9568.2003.02902.x
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发表时间：
2003-09-01
影响因子：
3.4
通讯作者：
Harrison, PJ
中科院分区：
文献类型：
--
作者：
Harris, LW;Sharp, T;Harrison, PJ
据报道，对新生大鼠进行短暂的 N-甲基-D-天冬氨酸 (NMDA) 受体阻断会增加神经元凋亡。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。在成年期，接受治疗的大鼠表现出海马内体积和神经元数量减少，并且海马 NMDA 受体（NR1 亚基）表达发生改变。丘脑（背侧核）中的突触素 mRNA 减少。接受 MK-801 治疗的成年雌性存在前脉冲抑制缺陷和运动活动增加。数据表明，发育过程中短暂且有限的谷氨酸能干预可能会产生慢性行为、结构和分子影响。这些效应让人想起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疾病的神经发育发病机制中起作用的假设是一致的。
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.