NEUROTOXIC EFFECTS OF NEONATAL TRIETHYLTIN (TET) EXPOSURE ARE EXACERBATED WITH AGING
NEUROTOXIC EFFECTS OF NEONATAL TRIETHYLTIN (TET) EXPOSURE ARE EXACERBATED WITH AGING
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DOI：
10.1016/0197-4580(95)00089-w
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发表时间：
1995-09-01
影响因子：
4.2
通讯作者：
MUNDY, WR
中科院分区：
文献类型：
--
作者：
BARONE, S;STANTON, ME;MUNDY, WR
新生Long-Evans大鼠在出生后第10天给予粉防己碱(5 mg/kg；ip)或生理盐水，观察其整个生命周期的神经损伤和空间学习任务。于给药后第2、7、14天处死一部分大鼠，用尼氏染色、Timm‘s组织化学和胶质纤维酸性蛋白(GFAP)免疫组织化学方法评价早期损伤。分别于给药后3、12、24个月在T迷宫空间延迟交替任务和Morris水迷宫位置学习任务中测试仔鼠的行为，然后处死动物进行组织学分析。在新生大鼠中，组织学分析显示离散皮质区域的胶质细胞增生，海马结构、内嗅皮层和梨状皮质尼氏染色神经元的缺失，内嗅皮层的Timm‘s染色缺失。PND 23时的行为学评估显示T迷宫明显受损。然而，在给药后3个月的T迷宫和3个月或12个月的水迷宫中没有观察到明显的损害。在24个月时，与年龄匹配的对照组相比，Tet处理的大鼠在水迷宫任务的习得和保持方面表现出显著的缺陷。与年轻的对照组相比，两组24月龄的大鼠都受到了显著的损害。24个月时，Tet处理组大鼠大脑皮层TIMM‘s染色的光密度随年龄增长而下降(9%)，内嗅皮层和海马齿状回外层分子层进一步减少(30%)。这些数据表明，早期发育暴露于有机金属会导致形态损害，这种损害仅在出生后早期发育和高龄时才表现出明显的行为损害。
Neonatal Long-Evans rats dosed with TET (5 mg/kg; IP) or saline on postnatal day (PND) 10 were examined across the life span for neural damage and performance on spatial learning tasks. A subset of rats were sacrificed to assess early damage with Nissl-staining, Timm's histochemistry, and glial fibrillary acidic protein (GFAP) immunohistochemistry 2, 7, or 14 days after dosing. Littermates were tested behaviorally in a T-maze spatial delayed alternation task on PND 23 or PND 90, and in a Morris water maze place learning task at 3, 12, or 24 months postdosing and then sacrificed for histological analysis. In neonatal rats, histological analysis indicated gliosis in discrete cortical regions, loss of Nissl-stained neurons in the hippocampal formation, entorhinal cortex and piriform cortex, and loss of Timm's staining in the entorhinal cortex. The behavioral assessment at PND 23 indicated a significant impairment in the T-maze. However, no significant impairments were observed in the T-maze at 3 months or the water maze at 3 or 12 months postdosing. At 24 months, TET-treated rats showed significant deficits in acquisition and retention of the water maze task compared with age-matched controls. Both groups of 24 months old rats were significantly impaired compared with young controls. At 24 months, there was a general age-related decrease in the optical density of Timm's staining in cortical regions (9%), compounded by a further decrease in the entorhinal cortex and outer molecular Layer of the dentate gyrus of the hippocampus in TET treated rats (30%). These data indicate that early developmental exposure to an organometal resulted in morphological damage that was apparent behaviorally only during early postnatal development and with advanced aging.