文章基本信息

标题：Developmental disruption of serotonin transporter function impairs cerebral responses to whisker stimulation in mice
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作者：Takanori Esaki ; Michelle Cook ; Kazuaki Shimoji 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：15
页码：5582-5587
DOI：10.1073/pnas.0501509102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：There is growing evidence that serotonin (5-hydroxtryptamine, 5-HT) has major influences on brain development in mammals. Genetic and pharmacological disruption of 5-HT signaling during early postnatal development in rodents causes neuroanatomical cortical abnormalities, including malformations in the somatosensory cortex. Possible functional consequences of this developmental perturbation by 5-HT are not yet understood. We have examined the effects of deletion of the 5-HT transporter (5-HTT) gene on somatosensory responses to sensory stimulation in mice. Local cerebral glucose utilization (lCMRglc) was measured by the quantitative 2-deoxy[14C]glucose method during unilateral whisker stimulation in awake adult mice. lCMRglc was increased by stimulation but to a markedly lesser extent in 5-HTT-/- mice than in 5-HTT+/+ controls in each of four major stations in the whisker-to-barrel cortex pathway (the spinal and principal sensory trigeminal nuclei, the ventral posteromedial thalamic nucleus, and the barrel region of the somatosensory cortex). Lowering brain 5-HT levels by administration of the selective tryptophan hydroxylase inhibitor p-chlorophenylalanine on postnatal days 0 and 1 restored the metabolic responses to functional activation in the whisker-to-barrel cortex pathway in adult 5-HTT-/- mice. These results indicate that functional deficits in this pathway in 5-HTT-/- mice may be due to excessive postnatal 5-HT activity. With or without postnatal p-chlorophenylalanine treatment, 5-HTT-/- mice exhibited lower resting (unstimulated) lCMRglc than did 5-HTT+/+ controls in the whisker-to-barrel cortex pathway and throughout the brain. These findings have implications for understanding the potential long-term consequences of genetic and pharmacological disruption of 5-HT neurotransmission on cerebral functions during critical periods of postnatal development.
关键词：cerebral glucose utilization ; cerebral metabolism ; 2-deoxy[14C]glucose