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Deficits in pattern separation and dentate gyrus proliferation after rodent lateral fluid percussion injury

机译:在啮齿动物横向流体冲击损伤后的模式分离和牙齿转化的缺陷

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摘要

It has been demonstrated that adult born granule cells are generated after traumatic brain injury (TBI). There is evidence that these newly generated neurons are aberrant and are poised to contribute to poor cognitive function after TBI. Yet, there is also evidence that these newly generated neurons are important for cognitive recovery. Pattern separation is a cognitive task known to be dependent on the function of adult generated granule cells. Performance on this task and the relation to dentate gyrus dysfunction after TBI has not been previously studied. Here we subjected Sprague Dawley rats to lateral fluid percussion injury or sham and tested them on the dentate gyrus dependent task pattern separation. At 2 weeks after injury, we examined common markers of dentate gyrus function such as GSK3ß phosphorylation, Ki-67 immunohistochemistry, and generation of adult born granule cells. We found that injured animals have deficits in pattern separation. We additionally found a decrease in proliferative capacity at 2 weeks indicated by decreased phosphorylation of GSK3ß and Ki-67 immunopositivity as compared to sham animals. Lastly we found an increase in numbers of new neurons generated during the pattern separation task. These findings provide evidence that dentate gyrus dysfunction may be an important contributor to TBI pathology.
机译:已经证明,成人出生的颗粒细胞在创伤性脑损伤(TBI)后产生。有证据表明,这些新生成的神经元是异常的,并且有助于在TBI后的认知功能差。然而,还有证据表明这些新生成的神经元对认知恢复很重要。模式分离是已知的认知任务,其依赖于成人生成的颗粒细胞的功能。在此任务上的性能和TBI尚未研究TBI后的牙齿过度功能障碍的关系。在这里,我们将Sprague Dawley大鼠进行横向流体冲击损伤或假,并在仪式回转依赖性任务模式分离上测试它们。在损伤后2周,我们检查了牙齿的常见功能的常见标记,如Gsk3ß磷酸化,Ki-67免疫组化,以及成人出生颗粒细胞的产生。我们发现受伤的动物在模式分离中具有缺陷。与假动物相比,我们另外发现通过降低GSK3β和Ki-67免疫阳性的磷酸化表明的2周内的增殖能力降低。最后,我们发现在模式分离任务期间产生的新神经元数量增加。这些发现提供了证据,即牙齿过滤功能障碍可能是TBI病理学的重要贡献者。

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