Paterson David S, Thompson Eric G, Kinney Hannah C
Department of Pathology, Enders 1111, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, United States; Harvard Medical School, Boston, MA 02115, USA.
Auton Neurosci. 2006 Jan 30;124(1-2):112-24. doi: 10.1016/j.autneu.2005.12.009. Epub 2006 Feb 2.
Central chemoreception is the mechanism by which the brain detects the level of carbon dioxide (CO(2)) in the arterial blood and alters breathing accordingly in order to maintain it within physiological levels. The ventral surface of the medulla oblongata (VMS) of animals has long been recognized as a site of chemosensitivity, culminating in the recent identification of chemosensitive serotonergic (5-HT) and glutamatergic (Glut) neurons in this region. In this study, we analyzed the distribution of 5-HT and Glut neurons and their receptors in the arcuate nucleus (Arc) at the VMS of the human infant, using single-and double-label immunohistochemistry with specific antibodies. We also examined the expression of astrocytes, as experimental evidence suggests that astrocytes mediate, at least in part, central chemosensitivity via 5-HT and/or Glut receptors. We identified a small number of 5-HT neurons (approximately 5% of Arc neurons), distributed over the entire extent of the VMS, a large number of Glut neurons (approximately 95% of Arc neurons) that localized almost exclusively to the medial Arc, and a large number of astrocytes distributed across the entire extent of the VMS. The Arc also contained 5-HT(1A), kainate (GluR5), and 5-HT(2A) receptors, which localized predominantly to 5-HT neurons, glutamate neurons and astrocytes, respectively. Astrocytes also expressed the vesicular glutamate transporter 2 and low levels of 5-HT(1A) and kainate (GluR5) receptors, indicating that astrocytes may store and release glutamate, possibly in response to stimulation by 5-HT and/or Glut. These observations suggest that important functional interactions exist between 5-HT, glutamate, and astrocytes in the Arc. They also support the idea that the Arc is homologous to chemosensitive zones at the VMS in experimental animals. These data are important towards delineating the role of the human Arc in modulation of homeostasis, and its dysfunction in brainstem-associated pathologies such as the sudden infant death syndrome.
中枢化学感受是大脑检测动脉血中二氧化碳（CO₂）水平并相应改变呼吸以将其维持在生理水平的机制。动物延髓腹侧面（VMS）长期以来一直被认为是化学敏感部位，最近在该区域鉴定出化学敏感的血清素能（5-HT）和谷氨酸能（Glut）神经元。在本研究中，我们使用特异性抗体的单标和双标免疫组织化学方法，分析了人类婴儿VMS处弓状核（Arc）中5-HT和Glut神经元及其受体的分布。我们还检测了星形胶质细胞的表达，因为实验证据表明星形胶质细胞至少部分地通过5-HT和/或Glut受体介导中枢化学敏感性。我们鉴定出少量5-HT神经元（约占Arc神经元的5%），分布在VMS的整个范围内，大量Glut神经元（约占Arc神经元的95%）几乎完全位于内侧Arc，以及大量星形胶质细胞分布在VMS的整个范围内。Arc还含有5-HT₁A、海人藻酸（GluR5）和5-HT₂A受体，它们分别主要定位于5-HT神经元、谷氨酸能神经元和星形胶质细胞。星形胶质细胞还表达囊泡谷氨酸转运体2以及低水平的5-HT₁A和海人藻酸（GluR5）受体，表明星形胶质细胞可能储存和释放谷氨酸，可能是对5-HT和/或Glut刺激的反应。这些观察结果表明，Arc中的5-HT、谷氨酸和星形胶质细胞之间存在重要的功能相互作用。它们还支持Arc与实验动物VMS处化学敏感区同源的观点。这些数据对于阐明人类Arc在调节体内平衡中的作用及其在与脑干相关的疾病如婴儿猝死综合征中的功能障碍具有重要意义。
