Increased hippocampal cell density and enhanced spatial memory in the valproic acid rat model of autism
Increased hippocampal cell density and enhanced spatial memory in the valproic acid rat model of autism
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DOI：
10.1016/j.brainres.2013.06.024
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发表时间：
2013-08-14
期刊：
影响因子：
2.9
通讯作者：
Moghadas, Marzieh
中科院分区：
文献类型：
--
作者：
Edalatmanesh, Mohammad Amin;Nikfarjam, Haniyeh;Moghadas, Marzieh
自闭症的特点是在三个主要领域存在行为障碍：社交互动；语言、沟通和想象力游戏；以及兴趣和活动的范围。然而，神经元处理研究表明，感知过度、注意力过度和记忆力增强可能是大多数自闭症症状的核心。在胚胎第 12.5 天的胎儿神经管发育过程中，给怀孕 Wistar 大鼠注射丙戊酸（VPA，500 mg/kg）或磷酸盐缓冲盐水（PBS）。所有后代都接受了各种测试。本研究考察了社交互动、重复行为、伤害感受和触觉阈值、焦虑以及空间记忆。对海马五个区域的细胞进行组织学分析，以确定两组的神经元密度。对怀孕大鼠进行单次腹腔注射 VPA 会在后代中产生严重的自闭症样症状。结果显示出显着的行为障碍，例如出生后 (PND) 30 和 PND 60 时发起社交互动的倾向较低、刻板、重复行为增强、伤害感受阈值增加和焦虑。莫里斯水迷宫学习范式显示 PND 60 时空间记忆增强。此外，组织学分析表明海马五个不同区域（CA1、CA2、CA3、齿状陀螺和下托）的神经元密度在出生后 60 时增加。 PND 67. 这项工作表明，大鼠早期胚胎暴露于 VPA 为自闭症的几个特定方面提供了一个良好的模型，并且应有助于继续探索病理生理学和神经解剖学假设。这项研究提供了进一步的证据来支持自闭症动物模型中空间记忆和海马细胞密度增加的观点。由 Elsevier B.V. 出版
Autism is characterized by behavioral impairments in three main domains: social interaction; language, communication and imaginative play; and the range of interests and activities. However, neuronal processing studies have suggested that hyper-perception, hyper-attention, and enhanced memory, which may lie at the heart of most autistic symptoms. Pregnant Wistar rats were administered by either Valproic Acid (VPA, 500 mg/kg) or Phosphate Buffer Saline (PBS) during fetal neural tube development on embryonic day 12.5. All offspring were subjected to various tests. The present study examined social interaction, repetitive behaviors, nociception and tactile threshold, anxiety as well as spatial memory. Histological analyses of cells in five regions of the hippocampus were done to determine neuronal density in both groups. A single intra-peritoneal injection of VPA to pregnant rats produced severe autistic-like symptoms in the offspring. The results showed significant behavioral impairments such as a lower tendency to initiate social interactions, enhanced stereotyped, repetitive behaviors, increased nociception threshold and anxiety at postnatal day (PND) 30 and PND 60. The Morris water maze learning paradigm revealed enhanced spatial memory at PND 60. Furthermore, histological analysis showed that the neuronal density in five separate regions of hippocampus (CA1, CA2, CA3, Dentate gyros and Subiculum) were increased at PND 67. This work suggests that early embryonic exposure to VPA in rats provides a good model for several specific aspects of autism and should help to continue to explore pathophysiological and neuroanatomical hypotheses. This study provides further evidence to support the notion that spatial memory and hippocampal cell density are increased in this animal model of autism. Published by Elsevier B.V.