Gizerian Samantha S, Morrow A Leslie, Lieberman Jeffrey A, Grobin A Chistina
Curriculum in Neurobiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
Brain Res. 2004 Jun 25;1012(1-2):66-74. doi: 10.1016/j.brainres.2004.03.049.
The neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one (allopregnanolone) is a potent endogenous modulator of GABAA receptor function. A single neonatal allopregnanolone administration (10 mg/kg, i.p.) was previously shown to alter the localization of parvalbumin-positive neurons in the prefrontal cortex at maturity. Cells in the prefrontal cortex receive the majority of their inputs from the medial dorsal nucleus of the thalamus. We investigated whether neonatal allopregnanolone administration alters the neuronal population of the medial dorsal nucleus of the thalamus. We show that the number of parvalbumin-expressing neurons is increased while the total neuron number is decreased in the medial dorsal nucleus after allopregnanolone administration. EAAT3 (excitatory amino acid transporter type 3, the neuron-specific glutamate reuptake transporter) immunoreactivity was unchanged in adjacent sections. These findings suggest that neonatal allopregnanolone administration disrupts the normal development of the prefrontal cortex and medial dorsal thalamus, indicating that neurosteroid levels are important for proper development of thalamocortical systems and may play a role in neurodevelopmental disorders such as schizophrenia.
神经活性甾体3α-羟基-5α-孕烷-20-酮(别孕烯醇酮)是γ-氨基丁酸A型(GABAA)受体功能的一种强效内源性调节剂。先前的研究表明,新生期单次给予别孕烯醇酮(10 mg/kg,腹腔注射)会改变成熟前额叶皮质中小清蛋白阳性神经元的定位。前额叶皮质中的细胞大部分输入来自丘脑背内侧核。我们研究了新生期给予别孕烯醇酮是否会改变丘脑背内侧核的神经元数量。我们发现,给予别孕烯醇酮后,丘脑背内侧核中表达小清蛋白的神经元数量增加,而神经元总数减少。相邻切片中兴奋性氨基酸转运体3(EAAT3,神经元特异性谷氨酸再摄取转运体)的免疫反应性未发生变化。这些发现表明,新生期给予别孕烯醇酮会破坏前额叶皮质和丘脑背内侧核的正常发育,这表明神经甾体水平对于丘脑皮质系统的正常发育很重要,并且可能在精神分裂症等神经发育障碍中发挥作用。