van Praag H, Qu P M, Elliott R C, Wu H, Dreyfus C F, Black I B
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, UMDNJ, Piscataway, NJ 08854, USA.
Behav Brain Res. 1998 Apr;92(1):21-30. doi: 10.1016/s0166-4328(97)00117-4.
Subcortical damage at birth often produces more severe deficits than similar lesions in an adult. In the present study, effects of unilateral electrolytic hippocampal ablations made on postnatal day 1 or in 3-month-old adult rats, were compared. Exploratory behavior and spatial navigation in the Morris water maze (MWM) were assessed 8 and 20 weeks after hippocampal damage. Rats with neonatal damage did not respond to novelty in the environment and did not learn to find the hidden platform in the MWM. Rats lesioned as adults did learn the water maze task, but slower than controls. We hypothesized that behavioral deficits observed in rats lesioned at birth, may be due, in part, to neurochemical dysfunction of the contralateral hippocampus. Specifically, cholinergic and GABAergic neurotransmission were assessed by measuring choline-acetyltransferase (ChAT) and GABAdecarboxylase (GAD) activity. In addition, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA levels were assayed in the remaining (contralateral) hippocampus. Of these molecules, only BDNF gene expression was significantly reduced (by 30%) at 8 and 20 weeks after neonatal and adult unilateral ablation. The similar reduction in BDNF mRNA in both treatment groups does not correspond with the lesion's differential effect on memory function. However, the more severe learning impairment after neonatal lesion may reflect increased dependence on trophins during development.
出生时的皮层下损伤通常比成人类似的损伤产生更严重的缺陷。在本研究中，比较了在出生后第1天或3个月大的成年大鼠身上进行单侧电解海马损毁的效果。在海马损伤后8周和20周评估了Morris水迷宫（MWM）中的探索行为和空间导航能力。新生期损伤的大鼠对环境中的新奇事物没有反应，也没有学会在MWM中找到隐藏平台。成年期损毁的大鼠确实学会了水迷宫任务，但比对照组慢。我们假设，出生时受损大鼠中观察到的行为缺陷，可能部分归因于对侧海马的神经化学功能障碍。具体而言，通过测量胆碱乙酰转移酶（ChAT）和GABA脱羧酶（GAD）活性来评估胆碱能和GABA能神经传递。此外，还检测了剩余（对侧）海马中神经生长因子（NGF）和脑源性神经营养因子（BDNF）的mRNA水平。在这些分子中，只有BDNF基因表达在新生期和成年期单侧损毁后8周和20周时显著降低（降低30%）。两个治疗组中BDNF mRNA的类似降低与损伤对记忆功能的不同影响不相符。然而，新生期损伤后更严重的学习障碍可能反映了发育过程中对神经营养因子的依赖性增加。
