In the current study, 5-nydroxytryptamine （5-HT） and gastrin （GAS） cells in the digestive canals of Rana chensinensis tadpoles at different developmental stages were investigated by immunohistochemistry. Results s...In the current study, 5-nydroxytryptamine （5-HT） and gastrin （GAS） cells in the digestive canals of Rana chensinensis tadpoles at different developmental stages were investigated by immunohistochemistry. Results showed that the 5-HT cells were only detected in the duodenum before metamorphosis began, and were extensively distributed in the stomach, duodenum, small intestine, and rectum thereafter, with the highest counts found in the duodenum and rectum when metamorphosis was completed. The GAS cells were only distributed in the stomach and duodenum, and only rarely detected in the duodenum before metamorphosis began, but increased in the stomach during metamorphosis and showed zonal distribution in the gastric mucosa when metamorphosis was completed. Metamorphosis is a critical period for amphibians, during which structural and functional physiological adaptations are required to transition from aquatic to terrestrial environments. During metamorphosis, the differentiations of 5-HT cells in the gastrointestinal canals of tadpoles could facilitate mucus secretion regulation, improve digestive canal lubrication, and help water- shortage food digestion in terrestrial environments. Conversely, GAS cell differentiations during metamorphosis might contribute to the digestive and absorptive function transition from herbivore to omnivore.展开更多
Early appearance of the serotonergic system in the fetal brain and the various effects of serotonin (5-HT) on brain morphogenesis, have given support to a neurotrophic role of serotonin. This function of serotonin is ...Early appearance of the serotonergic system in the fetal brain and the various effects of serotonin (5-HT) on brain morphogenesis, have given support to a neurotrophic role of serotonin. This function of serotonin is accomplished through a system of serotonin nerve terminals in the target regions that involves various 5-HT receptors. In visual, auditory and somatosensory cortex an early and intense serotonergic innervation is particularly important. The neuronal somata of these terminals are normally located in the mesencephalon and they have not been observed in the maturing cerebral cortex, neither in the adult brain. By using immunolabeling techniques, fluorescence and confocal microscopy, we observe the presence of both, 5-HT terminals and 5-HT cells in mesencephalon (Me, E17) and in the neopallium (Np, E13-E16) cocultures. Cells immunopositive to 5-HT and to tryptophan-5-hydroxilase are also observed in the Np on day 12 of culture. These results concerning the unexpected presence of serotonergic cells in the fetal cerebral cortex are interesting and may be of importance in corticogenesis. As it happens with other elements of the serotonergic system, the presence of these phenotypically serotonergic cells in the early cerebral cortex may be transitory and probably supporting cortex maturation processes. The molecular signaling path of the 5-HT1A receptor has also been identified.展开更多
The present study examines the effects of serotonin (5-HT) 1A receptor ligands on humoral im-mune response in two rat lines selected for over 75 generations for the enhancement or elimination of aggression. Activation...The present study examines the effects of serotonin (5-HT) 1A receptor ligands on humoral im-mune response in two rat lines selected for over 75 generations for the enhancement or elimination of aggression. Activation of presynaptic 5-HT1A receptors with a low dose of the selective 5-HT1A receptor agonist 8-OH-DPAT (0.1 mg/kg) or the blockade of postsynaptic 5-HT1A receptors with the antagonist WAY-100635 (1.0 mg/kg) did not affect the numbers of IgM-antibody forming cells (IgM-AFC) in the spleen of highly aggressive rats, which were characterized by higher immune responsiveness compared to nonaggressive line. On the other hand, the same doses of 8-OH-DPAT and WAY-100635, as well as a higher dose of 8-OH-DPAT (1.0 mg/kg), which is known to activate postsynaptic 5-HT1A receptors, produce immunostimulation in nonaggressive rats. However, only the highest dose of 8-OH-DPAT (5.0 mg/kg) was able to cause immunosuppression in nonaggressive rats that was mainly dependent on stimulation of postsynaptic 5-HT1A receptors. In contrast to nonaggressive rats, the dose of 1.0 mg/kg 8-OH-DPAT was sufficient to produce a decrease in the numbers of IgM-AFC in highly aggressive rats. Thus, pharmacological activation of pre- and postsynaptic 5-HT1A receptors, as well as the blockade of postsynaptic 5-HT1A receptors, produced different effects on the immune response in two lines of rats selected for high level of aggression or its absence. These data may have implications for more efficient treatments of a number of mental disorders associated with abnormal aggression.展开更多
Previously, we reported that changes induced in autonomic neurotransmission in rats by Lactobacillus brevis SBC8803 may be mediated by serotonin 3 (5-HT3) receptors. In this study, we evaluated the effects of heat-kil...Previously, we reported that changes induced in autonomic neurotransmission in rats by Lactobacillus brevis SBC8803 may be mediated by serotonin 3 (5-HT3) receptors. In this study, we evaluated the effects of heat-killed L. brevis SBC8803 on serotonin (5-HT) releasing from intestinal cells. In the in vitro study, L. brevis SBC8803 stimulated 5-HT release from cultured rat endocrine RIN-14B cells (SBC8803 vs. sterile water;P in vivo study, 2 mg of heat-killed L. brevis SBC8803 was administered using a stomach sonde (feeding needle) to C57BL/6J mice. Analysis of plasma by ELISA showed gradually increase in 5-HT concentrations (0 min vs. 60 min;P ex vivo cultured intestinal loops composed of duodenum and part of the jejunum, from C3H/HeN and C57BL/6J male mice indicated that L. brevis SBC8803 effectively induced 5-HT release (SBC8803 vs. sterile water;P L. brevis SBC8803 may stimulate 5-HT release from mouse intestinal cells such as enterochromaffin cells.展开更多
A series of 1-[2-（2-methoxyphenylthio） benzyl]-4-arylpiperazines derivatives was designed and synthesized based on 5-HT1A/ SSRI drugs design strategies. The synthesized compounds were evaluated for their dual 5-HT1A...A series of 1-[2-（2-methoxyphenylthio） benzyl]-4-arylpiperazines derivatives was designed and synthesized based on 5-HT1A/ SSRI drugs design strategies. The synthesized compounds were evaluated for their dual 5-HT1A/5-HTT activities. 2007 Ai Jun Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.展开更多
A series of 1-（N-（2-（2-methoxyphenylthio）benzyl）-N-methylamino-3-aryloxypropan-2-ols derivatives were designed and synthesized based on 5-HT1A/SSRI drugs design strategies. The synthesized compounds were evaluate...A series of 1-（N-（2-（2-methoxyphenylthio）benzyl）-N-methylamino-3-aryloxypropan-2-ols derivatives were designed and synthesized based on 5-HT1A/SSRI drugs design strategies. The synthesized compounds were evaluated for their dual 5-HT1A/ 5-HTT activities. 2007 Ai Jun Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.展开更多
Steroid hormones participate in the modulation of serotonergic transmission, including the regulation of synthetic and metabolic enzyme production, as well as receptor and transporter activity. The changes of 5-HT5A a...Steroid hormones participate in the modulation of serotonergic transmission, including the regulation of synthetic and metabolic enzyme production, as well as receptor and transporter activity. The changes of 5-HT5A and 5-HT2c immunolabeling induced by steroids in the hippocampus ofovariectomized rats were studied in this work. Densitometric analysis in rat hippocampi were carried out for adjacent brain coronal immunolabeled sections after treatment with subcutaneous injections of vehicle, estradiol, progesterone or the combination of both steroids in ovariectomized rats. Exposure to estradiol and the combination of estradiol and progesterone significantly reduced the 5-HT5A-like immunosignal in the CA 1 region while progesterone did not induce changes. On the other hand, exposure to the combination of estradiol and progesterone or estradiol alone increased the 5-HT2c immunosignal in the same region. These results indicate that estradiol is involved in the discrete regulation of serotonin receptors 5-HT5A and 5-HT2c in rat hippocampus.展开更多
Serotonin 5-HT2A receptors are playing an important role in the pathophysiology of aggressive behaviors and in the control of immune function. In the present study, we analyzed the effects of activation and blockade o...Serotonin 5-HT2A receptors are playing an important role in the pathophysiology of aggressive behaviors and in the control of immune function. In the present study, we analyzed the effects of activation and blockade of 5-HT2A receptors with selective ligands on the immune response formation in animals with aggressive behaviors induced by genetic factors (rats selected for the increased aggressiveness toward human) or by chronic social stress (mice of the CBA/Lac strain engaged in 10 days of social confrontations). Activation of 5-HT2A receptors with DOI at 1.0 mg/kg reduced the immune response level both in aggressive rats and mice compared to the corresponding vehicle-treated groups, while DOI administration did not alter the immune reaction in nonaggressive animals. The blockade of 5-HT2A receptors with ketanserin at 1.0 mg/kg resulted in immunostimulation both in mice of the CBA strain not subjected to social stress (the controls) and in nonaggressive rats selected for elimination of aggressiveness. On the other hand, its administration to CBA mice demonstrating offensive aggression enhanced the immune reaction, while the same dose of ketanserin did not modify the immune response level in rats with genetic predisposition to the increased defensive aggression. Thus, our data suggest that the role of 5-HT2A receptors in immunomodulation depends on the specific type of aggression that may be taking into account in the treatment of some neuropsychiatric disorders with the antipsychotic drugs and antidepressants targeting 5-HT2A receptors.展开更多
Previous studies suggest that serotonin （5-HT） might interact with brain-derived neurotrophic factor （BDNF） during the stress response. However, the relationship between 5-HT and BDNF expression under purely psych...Previous studies suggest that serotonin （5-HT） might interact with brain-derived neurotrophic factor （BDNF） during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry and in situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no significant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our findings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.展开更多
基金This study was supported by the Natural Science Foundation of Shaanxi Province （SJ08C101） and the Fundamental Research Funds for the Central Universities （GK200902039）.
文摘In the current study, 5-nydroxytryptamine （5-HT） and gastrin （GAS） cells in the digestive canals of Rana chensinensis tadpoles at different developmental stages were investigated by immunohistochemistry. Results showed that the 5-HT cells were only detected in the duodenum before metamorphosis began, and were extensively distributed in the stomach, duodenum, small intestine, and rectum thereafter, with the highest counts found in the duodenum and rectum when metamorphosis was completed. The GAS cells were only distributed in the stomach and duodenum, and only rarely detected in the duodenum before metamorphosis began, but increased in the stomach during metamorphosis and showed zonal distribution in the gastric mucosa when metamorphosis was completed. Metamorphosis is a critical period for amphibians, during which structural and functional physiological adaptations are required to transition from aquatic to terrestrial environments. During metamorphosis, the differentiations of 5-HT cells in the gastrointestinal canals of tadpoles could facilitate mucus secretion regulation, improve digestive canal lubrication, and help water- shortage food digestion in terrestrial environments. Conversely, GAS cell differentiations during metamorphosis might contribute to the digestive and absorptive function transition from herbivore to omnivore.
文摘Early appearance of the serotonergic system in the fetal brain and the various effects of serotonin (5-HT) on brain morphogenesis, have given support to a neurotrophic role of serotonin. This function of serotonin is accomplished through a system of serotonin nerve terminals in the target regions that involves various 5-HT receptors. In visual, auditory and somatosensory cortex an early and intense serotonergic innervation is particularly important. The neuronal somata of these terminals are normally located in the mesencephalon and they have not been observed in the maturing cerebral cortex, neither in the adult brain. By using immunolabeling techniques, fluorescence and confocal microscopy, we observe the presence of both, 5-HT terminals and 5-HT cells in mesencephalon (Me, E17) and in the neopallium (Np, E13-E16) cocultures. Cells immunopositive to 5-HT and to tryptophan-5-hydroxilase are also observed in the Np on day 12 of culture. These results concerning the unexpected presence of serotonergic cells in the fetal cerebral cortex are interesting and may be of importance in corticogenesis. As it happens with other elements of the serotonergic system, the presence of these phenotypically serotonergic cells in the early cerebral cortex may be transitory and probably supporting cortex maturation processes. The molecular signaling path of the 5-HT1A receptor has also been identified.
文摘The present study examines the effects of serotonin (5-HT) 1A receptor ligands on humoral im-mune response in two rat lines selected for over 75 generations for the enhancement or elimination of aggression. Activation of presynaptic 5-HT1A receptors with a low dose of the selective 5-HT1A receptor agonist 8-OH-DPAT (0.1 mg/kg) or the blockade of postsynaptic 5-HT1A receptors with the antagonist WAY-100635 (1.0 mg/kg) did not affect the numbers of IgM-antibody forming cells (IgM-AFC) in the spleen of highly aggressive rats, which were characterized by higher immune responsiveness compared to nonaggressive line. On the other hand, the same doses of 8-OH-DPAT and WAY-100635, as well as a higher dose of 8-OH-DPAT (1.0 mg/kg), which is known to activate postsynaptic 5-HT1A receptors, produce immunostimulation in nonaggressive rats. However, only the highest dose of 8-OH-DPAT (5.0 mg/kg) was able to cause immunosuppression in nonaggressive rats that was mainly dependent on stimulation of postsynaptic 5-HT1A receptors. In contrast to nonaggressive rats, the dose of 1.0 mg/kg 8-OH-DPAT was sufficient to produce a decrease in the numbers of IgM-AFC in highly aggressive rats. Thus, pharmacological activation of pre- and postsynaptic 5-HT1A receptors, as well as the blockade of postsynaptic 5-HT1A receptors, produced different effects on the immune response in two lines of rats selected for high level of aggression or its absence. These data may have implications for more efficient treatments of a number of mental disorders associated with abnormal aggression.
文摘Previously, we reported that changes induced in autonomic neurotransmission in rats by Lactobacillus brevis SBC8803 may be mediated by serotonin 3 (5-HT3) receptors. In this study, we evaluated the effects of heat-killed L. brevis SBC8803 on serotonin (5-HT) releasing from intestinal cells. In the in vitro study, L. brevis SBC8803 stimulated 5-HT release from cultured rat endocrine RIN-14B cells (SBC8803 vs. sterile water;P in vivo study, 2 mg of heat-killed L. brevis SBC8803 was administered using a stomach sonde (feeding needle) to C57BL/6J mice. Analysis of plasma by ELISA showed gradually increase in 5-HT concentrations (0 min vs. 60 min;P ex vivo cultured intestinal loops composed of duodenum and part of the jejunum, from C3H/HeN and C57BL/6J male mice indicated that L. brevis SBC8803 effectively induced 5-HT release (SBC8803 vs. sterile water;P L. brevis SBC8803 may stimulate 5-HT release from mouse intestinal cells such as enterochromaffin cells.
基金This work was supported by the National Natural Science Foundation of China （No. 20576094）.
文摘A series of 1-[2-（2-methoxyphenylthio） benzyl]-4-arylpiperazines derivatives was designed and synthesized based on 5-HT1A/ SSRI drugs design strategies. The synthesized compounds were evaluated for their dual 5-HT1A/5-HTT activities. 2007 Ai Jun Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
基金This work was supported by the National Natural Science Foundation of China （No. 20576094）.
文摘A series of 1-（N-（2-（2-methoxyphenylthio）benzyl）-N-methylamino-3-aryloxypropan-2-ols derivatives were designed and synthesized based on 5-HT1A/SSRI drugs design strategies. The synthesized compounds were evaluated for their dual 5-HT1A/ 5-HTT activities. 2007 Ai Jun Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
文摘Steroid hormones participate in the modulation of serotonergic transmission, including the regulation of synthetic and metabolic enzyme production, as well as receptor and transporter activity. The changes of 5-HT5A and 5-HT2c immunolabeling induced by steroids in the hippocampus ofovariectomized rats were studied in this work. Densitometric analysis in rat hippocampi were carried out for adjacent brain coronal immunolabeled sections after treatment with subcutaneous injections of vehicle, estradiol, progesterone or the combination of both steroids in ovariectomized rats. Exposure to estradiol and the combination of estradiol and progesterone significantly reduced the 5-HT5A-like immunosignal in the CA 1 region while progesterone did not induce changes. On the other hand, exposure to the combination of estradiol and progesterone or estradiol alone increased the 5-HT2c immunosignal in the same region. These results indicate that estradiol is involved in the discrete regulation of serotonin receptors 5-HT5A and 5-HT2c in rat hippocampus.
文摘Serotonin 5-HT2A receptors are playing an important role in the pathophysiology of aggressive behaviors and in the control of immune function. In the present study, we analyzed the effects of activation and blockade of 5-HT2A receptors with selective ligands on the immune response formation in animals with aggressive behaviors induced by genetic factors (rats selected for the increased aggressiveness toward human) or by chronic social stress (mice of the CBA/Lac strain engaged in 10 days of social confrontations). Activation of 5-HT2A receptors with DOI at 1.0 mg/kg reduced the immune response level both in aggressive rats and mice compared to the corresponding vehicle-treated groups, while DOI administration did not alter the immune reaction in nonaggressive animals. The blockade of 5-HT2A receptors with ketanserin at 1.0 mg/kg resulted in immunostimulation both in mice of the CBA strain not subjected to social stress (the controls) and in nonaggressive rats selected for elimination of aggressiveness. On the other hand, its administration to CBA mice demonstrating offensive aggression enhanced the immune reaction, while the same dose of ketanserin did not modify the immune response level in rats with genetic predisposition to the increased defensive aggression. Thus, our data suggest that the role of 5-HT2A receptors in immunomodulation depends on the specific type of aggression that may be taking into account in the treatment of some neuropsychiatric disorders with the antipsychotic drugs and antidepressants targeting 5-HT2A receptors.
基金supported by grants from the Natural Science Foundation of Shandong Province of China(ZR2011HM023 to GYL)the “11th Five-Year Plan”,National Supporting Program(2007BAI17B02 to GYL)+5 种基金the Science and Technology Project of Higher Education of Shandong Province of China(J10LF01 to GYL)a grant from Medical Science and Technology Development Project of Shandong Province of China(2011HZ011 to GYL)the China Postdoctoral Science Foundation of China(2012M 520585 to CJZ)the Fund of Tianjin Health Bureau of China(2014KR02 to CJZ)the Foundation of Hainan Li Ou Pharmaceutical Co.,Ltd.the Foundation of Xuzhou Enhua Pharmaceutical Co.,Ltd. of China
文摘Previous studies suggest that serotonin （5-HT） might interact with brain-derived neurotrophic factor （BDNF） during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry and in situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no significant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our findings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.
