Genetic Architecture and Functional Implications of the CSF-Contacting Nucleus / 神经科学通报·英文版

We previously identified a unique nucleus, the cerebrospinal fluid (CSF)-contacting nucleus. This study aims to understand its gene architecture and preliminarily suggest its functions. The results showed that there were about 19,666 genes in this nucleus, of which 913 were distinct from the dorsal raphe nucleus (non-CSF contacting). The top 40 highly-expressed genes are mainly related to energy metabolism, protein synthesis, transport, secretion, and hydrolysis. The main neurotransmitter is 5-HT. The receptors of 5-HT and GABA are abundant. The channels for Cl-, Na+, K+, and Ca2+ are routinely expressed. The signaling molecules associated with the CaMK, JAK, and MAPK pathways were identified accurately. In particular, the channels of transient receptor potential associated with nociceptors and the solute carrier superfamily members associated with cell membrane transport were significantly expressed. The relationship between the main genes of the nucleus and life activities is preliminarily verified.

Cerebrospinal fluid-contacting nucleus mediates nociception via release of fractalkine

Increasing evidence suggests that the cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) mediates the transduction and regulation of pain signals. However, the precise molecular mechanisms remain unclear. Studies show that release of fractalkine (FKN) from neurons plays a critical role in nerve injury-related pain. We tested the hypothesis that release of FKN from the CSF-contacting nucleus regulates neuropathic pain, in a chronic constriction injury rat model. The results show that FKN is expressed by neurons, via expression of its only receptor CX3CR1 in the microglia. The levels of soluble FKN (sFKN) were markedly upregulated along with the increase in FKN mRNA level in rats subjected to chronic constriction injury. In addition, injection of FKN-neutralizing antibody into the lateral ventricle alleviated neuropathic pain-related behavior followed by reduction in microglial activation in the CSF-contacting nucleus. The results indicate that inhibition of FKN release by the CSF-contacting nucleus may ameliorate neuropathic pain clinically.

Role of cerebrospinal fluid-contacting nuclei in maintenance of chronic itch in rats / 中华麻醉学杂志

Objective To evaluate the role of cerebrospinal fluid-contacting nuclei (CSF-CN) in maintenance of chronic itch in rats.Methods Forty-two adult male Sprague-Dawley rats,aged 3 months,weighing 240-280 g,were used in the study.The experiment was performed in two parts.Part Ⅰ Forty-two Sprague-Dawley rats were randomly divided into 3 groups (n =14 each):control group (C group),acetone group (A group) and oxazolone group (O group).0.5％ oxazolone 15 μl was applied to the neck and back of rats in group O,while the equal volume of normal saline and acetone was applied in groups C and A,respectively.Application of the drug mentioned above was repeated on day 7,9,13,16,17,18,21 and 23 after the first stimulation in each rat in each group.Scratching behaviors were oberserved within 30 min after each stimulaiton.Six rats in each group were chosen and sacrificed after the last application of oxazolone,and the brains were obtained for determination of c-Fos expression in CSF-CN.Part Ⅱ Twenty-four rats were randomly divided into 3 groups (n =8 each):control group (C1 group),chronic itch group (group CI),and chronic itch + lesion group (CI + KA group).Chronic itch was induced by repeated application of oxazolone as previously described in CI and CI + KA groups.The chemical lesion of CSF-CN was performed at 6 h after 8th application of the drug.Then the scratching behaviors were observed within 30 min after 9th application of the drug.Results Part Ⅰ Compared with C group,the scratching behaviors were increased significantly at T4-8 in A group,and at T1-8 in O group (P ＜ 0.05),and the expression of c-Fos was up-regulated in O and A groups (P ＜ 0.05).Compared with A group,the scratching behaviors were increased significantly at T1-8 and the expression of c-Fos was up-regulated in O group (P ＜ 0.05).Part Ⅱ Compared with C1 group,the scratching behaviors were significantly increased in CI and CI + KA groups (P ＜ 0.05).The scratching behaviors were significantly reduced in CI + KA group compared with CI group (P ＜ 0.05).Conclusion CSF-CN is involved in the maintenance of chronic itch in rats.