Takada Silvia Honda, Motta-Teixeira Lívia Clemente, Machado-Nils Aline Vilar, Lee Vitor Yonamine, Sampaio Carlos Alberto, Polli Roberson Saraiva, Malheiros Jackeline Moraes, Takase Luiz Fernando, Kihara Alexandre Hiroaki, Covolan Luciene, Xavier Gilberto Fernando, Nogueira Maria Inês
Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil; Núcleo de Cognição e Sistemas Complexos, Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, Santo André, Brazil.
Departamento de Fisiologia Geral, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
Behav Brain Res. 2016 Jan 1;296:331-338. doi: 10.1016/j.bbr.2015.08.039. Epub 2015 Sep 28.
Neonates that suffer oxygen deprivation during birth can have long lasting cognitive deficits, such as memory and learning impairments. Hippocampus, one of the main structures that participate in memory and learning processes, is a plastic and dynamic structure that conserves during life span the property of generating new cells which can become neurons, the so-called neurogenesis. The present study investigated whether a model of rat neonatal anoxia, that causes only respiratory distress, is able to alter the hippocampal volume, the neurogenesis rate and has functional implications in adult life. MRI analysis revealed significant hippocampal volume decrease in adult rats who had experienced neonatal anoxia compared to control animals for rostral, caudal and total hippocampus. In addition, these animals also had 55.7% decrease of double-labelled cells to BrdU and NeuN, reflecting a decrease in neurogenesis rate. Finally, behavioral analysis indicated that neonatal anoxia resulted in disruption of spatial working memory, similar to human condition, accompanied by an anxiogenic effect. The observed behavioral alterations caused by oxygen deprivation at birth might represent an outcome of the decreased hippocampal neurogenesis and volume, evidenced by immunohistochemistry and MRI analysis. Therefore, based on current findings we propose this model as suitable to explore new therapeutic approaches.
出生时遭受缺氧的新生儿可能会有长期的认知缺陷，如记忆和学习障碍。海马体是参与记忆和学习过程的主要结构之一，是一个具有可塑性和动态性的结构，在整个生命周期中都保留着产生新细胞（这些新细胞可成为神经元，即所谓的神经发生）的特性。本研究调查了一种仅导致呼吸窘迫的大鼠新生儿缺氧模型是否能够改变海马体体积、神经发生率，并对成年后的生活产生功能影响。MRI分析显示，与对照动物相比，经历过新生儿缺氧的成年大鼠的海马体体积在喙侧、尾侧和整个海马体均显著减小。此外，这些动物中双标记为BrdU和NeuN的细胞也减少了55.7%，这反映了神经发生率的降低。最后，行为分析表明，新生儿缺氧导致空间工作记忆受损，类似于人类情况，并伴有焦虑效应。出生时缺氧引起的观察到的行为改变可能是海马体神经发生和体积减少的结果，免疫组织化学和MRI分析证明了这一点。因此，基于目前的研究结果，我们认为该模型适合探索新的治疗方法。
