The Applied Neurotherapeutics Research Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Neuroscience. 2010 Mar 17;166(2):377-85. doi: 10.1016/j.neuroscience.2009.12.045. Epub 2009 Dec 24.
As the pathophysiological mechanism(s) of many neuropsychiatric disorders relate to GABAergic interneuron structure and function, we employed isolation rearing of Wistar rats as a model to correlate developmental emergence of cognitive deficits with the expression of reelin-producing interneurons in the medial prefrontal cortex (PFC). Prepulse inhibition deficits emerged at postnatal day 60 and persisted into adulthood. Paralleling the emergence of these neurobehavioural deficits was an increase in reelin production and reelin-immunopositive cells in layer I of the PFC and this later became significantly reduced at postnatal day 80. Cells expressing reelin immunoreactivity in a horizontal orientation were mainly located to the upper regions of layer I whereas those with a vertical orientation, whose arbors extend into cortical layers II and III, were more numerous in the lower regions of layer I and became significantly dysregulated during postnatal development. No behavioural deficits or altered reelin expression was observed at postnatal days 30 or 40. Developmental emergence of neurobehavioural and reelin deficits in isolation reared animals is proposed to reflect maladaptive wiring within the medial prefrontal cortex during a critical maturation period of this circuitry.
由于许多神经精神疾病的病理生理机制与 GABA 能中间神经元的结构和功能有关，我们采用 Wistar 大鼠隔离饲养作为模型，将认知缺陷的发育出现与内侧前额叶皮层（PFC）中产生 reelin 的中间神经元的表达相关联。条件性回避反应缺陷出现在出生后 60 天，并持续到成年期。与这些神经行为缺陷的出现平行的是，PFC 层 I 中 reelin 的产生和 reelin 免疫阳性细胞增加，而这种情况在出生后 80 天显著减少。以水平方向表达 reelin 免疫反应性的细胞主要位于层 I 的上部区域，而那些具有垂直方向的细胞，其树突延伸到皮质层 II 和 III，在层 I 的下部区域更为常见，并且在出生后的发育过程中显著失调。在出生后 30 或 40 天，没有观察到行为缺陷或 reelin 表达改变。在隔离饲养的动物中，神经行为和 reelin 缺陷的发育出现被认为反映了内侧前额叶皮层在这个回路的关键成熟期间的适应性布线不良。
