Objective To investigate the role of H1 and H2 receptors in the locus ceruleus （LC） in carotid sinus baroreceptor reflex （CSR） resetting induced by intracerebroventricular （i.c.v.） injection of histamine （HA）....Objective To investigate the role of H1 and H2 receptors in the locus ceruleus （LC） in carotid sinus baroreceptor reflex （CSR） resetting induced by intracerebroventricular （i.c.v.） injection of histamine （HA）. Methods The left and right carotid sinus regions were isolated from the systemic circulation in 18 male Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure （ISP） was altered in a stepwise manner in vivo. ISP-mean arterial pressure （MAP） relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CSR performance induced by i.c.v. HA and the effects of pretreatment with H1 or H2 receptors selective antagonist, chlorpheniramine （CHL） or cimetidine （CIM） into the LC, on the responses of CSR to HA were examined. Results I.c.v. HA （100 ng in 5 μl） significantly shifted the ISP-MAP relationship curve upwards （P 〈 0.05） and obviously decreased the value of the reflex parameters such as MAP range and maximum gain （P 〈 0.05）, but increased the threshold pressure, saturation pressure and ISP at maximum gain （P 〈 0.05）. The pretreatment with CHL （0.5 μg in 1 μl） or CIM （1.5 μg in 1 μl） into the LC could obviously attenuate the changes mentioned above in CSR performance induced by HA, but the alleviative effect of CIM was less remarkable than that of CHL （P 〈 0.05）. Respective microinjection of CHL or CIM alone into the LC with the corresponding dose and volume did not change CSR performance significantly （P 〉 0.05）. Conclusion Intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity, and the responses of CSR to HA may be mediated, at least in part, by H1 and H2 receptors activities in the LC, especially by H1 receptors. Moreover, the effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to LC.展开更多
Mice carrying mutant amyloid precursor protein and presenilin-1 genes （APP/PS1 double trans- genic mice） have frequently been used in studies of Alzheimer＇s disease; however, such studies have focused mainly on hip...Mice carrying mutant amyloid precursor protein and presenilin-1 genes （APP/PS1 double trans- genic mice） have frequently been used in studies of Alzheimer＇s disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer＇s disease is known to correlate with the amount of amyloid-13 protein deposition and the number of dead neurons in the locus coeruleus. In the present study, we assigned APP/PS1 double transgenic mice to two groups according to age： young mice （5-6 months old） and aged mice （16-17 months old）. Age-matched wild-type mice were used as controls. Immunohistochemistry for tyrosine hydroxylase （a marker of catecholaminergic neurons in the locus coeruleus） revealed that APP/PS1 mice had 23% fewer cells in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cell bodies of neurons positive for tyrosine hydroxylase, but fewer tyrosine hydroxylase-positive fibers, which were also short, thick and broken. Quantitative analysis using unbiased stereology showed a significant age-related increase in the mean volume of tyrosine hy- droxylase-positive neurons in aged APP/PS1 mice compared with young APP/PS1 mice. Moreover, the mean volume of tyrosine hydroxylase-positive neurons was positively correlated with the total volume of the locus coeruleus. These findings indicate that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in APP/PS1 double transgenic mice.展开更多
文摘Objective To investigate the role of H1 and H2 receptors in the locus ceruleus （LC） in carotid sinus baroreceptor reflex （CSR） resetting induced by intracerebroventricular （i.c.v.） injection of histamine （HA）. Methods The left and right carotid sinus regions were isolated from the systemic circulation in 18 male Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure （ISP） was altered in a stepwise manner in vivo. ISP-mean arterial pressure （MAP） relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CSR performance induced by i.c.v. HA and the effects of pretreatment with H1 or H2 receptors selective antagonist, chlorpheniramine （CHL） or cimetidine （CIM） into the LC, on the responses of CSR to HA were examined. Results I.c.v. HA （100 ng in 5 μl） significantly shifted the ISP-MAP relationship curve upwards （P 〈 0.05） and obviously decreased the value of the reflex parameters such as MAP range and maximum gain （P 〈 0.05）, but increased the threshold pressure, saturation pressure and ISP at maximum gain （P 〈 0.05）. The pretreatment with CHL （0.5 μg in 1 μl） or CIM （1.5 μg in 1 μl） into the LC could obviously attenuate the changes mentioned above in CSR performance induced by HA, but the alleviative effect of CIM was less remarkable than that of CHL （P 〈 0.05）. Respective microinjection of CHL or CIM alone into the LC with the corresponding dose and volume did not change CSR performance significantly （P 〉 0.05）. Conclusion Intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity, and the responses of CSR to HA may be mediated, at least in part, by H1 and H2 receptors activities in the LC, especially by H1 receptors. Moreover, the effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to LC.
基金supported by the National Natural Science Foundation of China, No. 81100663the Scientific Research Funds of the Health Department of Hunan Province, No.120303+1 种基金Hunan Provincal Natural Science Foundation of China, No. 13JJ3058a grant from the Scientific Research Program of Hunan Provincial Higher Education Institutes, No. 11C0829
文摘Mice carrying mutant amyloid precursor protein and presenilin-1 genes （APP/PS1 double trans- genic mice） have frequently been used in studies of Alzheimer＇s disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer＇s disease is known to correlate with the amount of amyloid-13 protein deposition and the number of dead neurons in the locus coeruleus. In the present study, we assigned APP/PS1 double transgenic mice to two groups according to age： young mice （5-6 months old） and aged mice （16-17 months old）. Age-matched wild-type mice were used as controls. Immunohistochemistry for tyrosine hydroxylase （a marker of catecholaminergic neurons in the locus coeruleus） revealed that APP/PS1 mice had 23% fewer cells in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cell bodies of neurons positive for tyrosine hydroxylase, but fewer tyrosine hydroxylase-positive fibers, which were also short, thick and broken. Quantitative analysis using unbiased stereology showed a significant age-related increase in the mean volume of tyrosine hy- droxylase-positive neurons in aged APP/PS1 mice compared with young APP/PS1 mice. Moreover, the mean volume of tyrosine hydroxylase-positive neurons was positively correlated with the total volume of the locus coeruleus. These findings indicate that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in APP/PS1 double transgenic mice.
