摘要
多巴胺转运蛋白(DAT)敲除(KO)小鼠显示许多的行为改变,包括快速移动、认知障碍、冲动和惊吓反射(PPI)的前脉冲抑制的损害,表型可能与体区疾病例如精神分裂症有关。锥体神经元的背外侧前额叶皮层(DLPFC)树突棘的变化是在精神分裂症解剖学研究中的研究结果的最吻合的地方。精神分裂症的DLPFC的树枝状改变的机制还不清楚。这里,我们报导在内侧前额叶皮质(mPFC)的锥体神经元的基底棘密度、运动皮质、海马的CA1区和在DAT KO小鼠基底外侧杏仁核。利用DAT KO小鼠和Thy1-GFP转基因老鼠杂交使得椎体神经元可视化。我们观察到与WT老鼠相比,在DAT KO老鼠的海马的mPFC和CA1区域的椎体神经元的树突棘密度显著减少。另一方面,在DAT基因型之间没有观察到在运动皮质或者基地外侧杏仁核中的锥体神经元的树突棘密度的差异。这些结果表明树突棘密度减少可能导致mPFC和海马的功能不良,及导致DAT KO老鼠的行为异常,包括认知障碍。这可能表明异常的多巴胺信号可能引发精神分裂症中的海马和前额皮质的锥体神经元的树突的营养不良。
关键词: 杏仁基底外侧核,树突,GFP转基因老鼠,海马体,内侧前额叶皮质,运动皮质,椎体细胞,树突棘密度
Current Molecular Medicine
Title:Region-Specific Dendritic Spine Loss of Pyramidal Neurons in Dopamine Transporter Knockout Mice
Volume: 15 Issue: 3
Author(s): Y. Kasahara, Y. Arime, F.S. Hall, G.R. Uhl and I. Sora
Affiliation:
关键词: 杏仁基底外侧核,树突,GFP转基因老鼠,海马体,内侧前额叶皮质,运动皮质,椎体细胞,树突棘密度
摘要: Dopamine transporter (DAT) knockout (KO) mice show numerous behavioral alterations, including hyperlocomotion, cognitive deficits, impulsivity and impairment of prepulse inhibition of the startle reflex (PPI), phenotypes that may be relevant to frontostriatal disorders such as schizophrenia. Dendritic spine changes of pyramidal neurons in the dorsolateral prefrontal cortex (DLPFC) are among the most replicated of findings in postmortem studies of schizophrenia. The mechanisms that account for dendritic changes in the DLPFC in schizophrenia are unclear. Here, we report basal spine density of pyramidal neurons in the medial prefrontal cortex (mPFC), the motor cortex, the CA1 region of the hippocampus, and the basolateral amygdala in DAT KO mice. Pyramidal neurons were visualized using DAT KO mice crossbred with a Thy1-GFP transgenic mouse line. We observed a significant decrease in spine density of pyramidal neurons in the mPFC and the CA1 region of the hippocampus in DAT KO mice compared to that in WT mice. On the other hand, no difference was observed in spine density of pyramidal neurons in the motor cortex or the basolateral amygdala between DAT genotypes. These results suggest that decreased spine density could cause hypofunction of the mPFC and the hippocampus, and contribute to the behavioral abnormalities observed in DAT KO mice, including cognitive deficits. This might suggest that aberrant dopaminergic signaling may trigger dystrophic changes in dendrites of hippocampal and prefrontocortical pyramidal neurons in schizophrenia.
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Cite this article as:
Y. Kasahara, Y. Arime, F.S. Hall, G.R. Uhl and I. Sora , Region-Specific Dendritic Spine Loss of Pyramidal Neurons in Dopamine Transporter Knockout Mice, Current Molecular Medicine 2015; 15 (3) . https://dx.doi.org/10.2174/1566524015666150330143613
DOI https://dx.doi.org/10.2174/1566524015666150330143613 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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