Abstract:Serotonin (5-hydroxytryptamine, 5-HT) dysfunction is associated with the pathophysiology of depression. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, is believed to have essential role in many mental disorders, including depression. In the present study, we generated a rat model of depression by exposing the animals to stress, and the rats were then treated with paroxetine. The results indicated that the concentration of 5-HT in the brain and liver tissues were significantly lowe… Show more
“…Therefore, since tryptophan hydroxylase is the enzyme responsible for the synthesis of serotonin, a TPH immunohistochemistry was carried out in the hypothalamic area to clarify the SQE mechanism that induced an elevation in the serotonin levels. The rats in control group exhibited a lower TPH-IR cells number in the hypothalamic nuclei as in this study [64], while the SQE 100 and 300 administration enhanced these cells significantly in the anterior hypothalamic nucleus (AN), ventromedial hypothalamic nucleus (VMH), paraventricular hypothalamic nucleus (PVN), and arcuate nucleus (Arc).…”
Background. Sasa quelpaertensis Nakai extract (SQE) or dwarf bamboo has been extensively investigated for its antioxidant and anti-inflammatory effects; however, no previous study assessed its effect as an antidepressant agent. Therefore, this study was designed to examine the effect of oral SQE administration in ameliorating menopausal depressive symptoms and to evaluate its mechanisms in ovariectomized rats with repeated stress. Methods. All experimental groups except normal group underwent ovariectomy and then immobilization for 14 consecutive days. During these 2 weeks, two rat groups received SQE (100 and 300 mg/kg orally) and their cutaneous body temperature was measured. The tail suspension test (TST) and forced swim test (FST) were performed in order to evaluate depression-like behavior. Additionally, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were carried out to evaluate the central monoaminergic neurotransmitter levels and activity. Results. Oral SQE (100 mg/kg) administration had reduced immobility time in TST and FST. Additionally, the SQE 100 and 300 mg/kg administration had decreased the cutaneous body temperature in the rats compared to those without treatment. In ELISA analysis, the SQE 100 group expressed elevated levels of serotonin and dopamine in the hypothalamus, prefrontal cortex, and hippocampus. Antityrosine hydroxylase (anti-TH) antibodies showed a tremendous increase in the density of TH positive cells in the locus coeruleus (LC) region of the SQE 100 group. Likewise, the SQE 100 elevated the number of tryptophan hydroxylase (TPH) and protein kinase C (PKC) immunoreactive cell counts and density in the hypothalamic region. Conclusion. These results suggested that the oral SQE administration induced the antidepressant-like effect in the ovariectomized rats with repeated stress via upregulating the levels of serotonin and dopamine through enhancing the expression of TH, TPH, and PKC in many brain areas.
“…Therefore, since tryptophan hydroxylase is the enzyme responsible for the synthesis of serotonin, a TPH immunohistochemistry was carried out in the hypothalamic area to clarify the SQE mechanism that induced an elevation in the serotonin levels. The rats in control group exhibited a lower TPH-IR cells number in the hypothalamic nuclei as in this study [64], while the SQE 100 and 300 administration enhanced these cells significantly in the anterior hypothalamic nucleus (AN), ventromedial hypothalamic nucleus (VMH), paraventricular hypothalamic nucleus (PVN), and arcuate nucleus (Arc).…”
Background. Sasa quelpaertensis Nakai extract (SQE) or dwarf bamboo has been extensively investigated for its antioxidant and anti-inflammatory effects; however, no previous study assessed its effect as an antidepressant agent. Therefore, this study was designed to examine the effect of oral SQE administration in ameliorating menopausal depressive symptoms and to evaluate its mechanisms in ovariectomized rats with repeated stress. Methods. All experimental groups except normal group underwent ovariectomy and then immobilization for 14 consecutive days. During these 2 weeks, two rat groups received SQE (100 and 300 mg/kg orally) and their cutaneous body temperature was measured. The tail suspension test (TST) and forced swim test (FST) were performed in order to evaluate depression-like behavior. Additionally, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were carried out to evaluate the central monoaminergic neurotransmitter levels and activity. Results. Oral SQE (100 mg/kg) administration had reduced immobility time in TST and FST. Additionally, the SQE 100 and 300 mg/kg administration had decreased the cutaneous body temperature in the rats compared to those without treatment. In ELISA analysis, the SQE 100 group expressed elevated levels of serotonin and dopamine in the hypothalamus, prefrontal cortex, and hippocampus. Antityrosine hydroxylase (anti-TH) antibodies showed a tremendous increase in the density of TH positive cells in the locus coeruleus (LC) region of the SQE 100 group. Likewise, the SQE 100 elevated the number of tryptophan hydroxylase (TPH) and protein kinase C (PKC) immunoreactive cell counts and density in the hypothalamic region. Conclusion. These results suggested that the oral SQE administration induced the antidepressant-like effect in the ovariectomized rats with repeated stress via upregulating the levels of serotonin and dopamine through enhancing the expression of TH, TPH, and PKC in many brain areas.
“…There are several conflicting studies on the expression pattern of TPH following exposure to stress. Still, it has been reported that the levels of 5-HT and TPH in the raphe nuclei of the brain stem are tightly linked to the development of a depressive disorder or depressive-like behaviors [ 28 – 30 ]. In the present study, although not statistically significant, all mice exposed to repeated RST showed a trend towards increased TPH expression selectively in the dorsal raphe nucleus, the largest serotonergic nucleus, depending on the duration of RST exposure.…”
C57BL/6NKorl mice are a novel mouse stock recently developed by the National Institute of Food and Drug Safety Evaluation in Korea. Extensive research into the nature of C57BL/6NKorl mice is being conducted. However, there is no scientific evidence for the phenotypic response to restraint stress (RST), a stress paradigm for modeling depressive disorders, in rodents. In this study, we investigated the repeated RST-induced depressive-like phenotypes in C57BL/6 N mouse substrains (viz., C57BL/6NKorl mice from Korea, C57BL/6NA mice from the United States, and C57BL/6NB mice from Japan) obtained from different sources. The results showed that C57BL/6 N mice derived from various sources exposed to repeated RST resulted in depressive-like phenotypes reflected by a similar degree of behavioral modification and susceptibility to oxidative stress in a duration-dependent manner, except for the distinctive features (increased body weight (BW) and tolerance to the suppression of BW gain by exposure to repeated RST) in C57BL/6NKorl mice. Taken together, the duration-dependent alteration in depressive-like phenotypes by repeated exposure to RST observed in this study may provide valuable insights into the nature of C57BL/6NKorl mice as an alternative animal resource for better understanding of the etiology of depressive disorders and the mechanisms of antidepressant actions.
“…The next main finding of our study was that chronic venlafaxine administration in stressed rats decreased Tph1 protein expression in the basal ganglia and decreased the methylation status of the Tph1 promoter region in PBMCs; however, no changes were observed in the brain. On the other hand, Chen et al ( 2017 ) observed that stressed rats showed increased levels of Tph1/Tph2 promoter methylation, which was normalized by paroxetine (an SSRI), in the brain, liver and kidney. These differences may be related to the fact that the stressors used in the above study were much more severe and that the animal breeds that were used differed between studies.…”
A growing body of evidence suggests that depression may be associated with impairment of the tryptophan catabolites (TRYCATs) pathway. The present study investigated the effects of the chronic administration of venlafaxine on the expression and methylation status of Katl, Tph1/2, Ido1, Kmo and Kynu in the brain and blood of rats exposed to the CMS model of depression. The rats were subjected to the CMS procedure for 2 or 7 weeks and administered venlafaxine (10 mg/kg/day, IP) for 5 weeks. mRNA and protein expression and the methylation status of gene promoters in PBMCs and six brain structures were evaluated and analysed using the TaqMan Gene Expression Assay and Western blotting, and methylation-sensitive high-resolution melting (MS-HRM), respectively. We found that the CMS procedure increased KatI expression in the midbrain and KatII expression in the midbrain and the amygdala, while venlafaxine administration decreased KatII expression in the hypothalamus and the cerebral cortex. The methylation status of the Tph1 and Kmo promoters in peripheral blood mononuclear cells (PBMCs) was significantly increased in the stressed group after antidepressant therapy. The protein levels of Tph1 and Ido1 were decreased following venlafaxine administration. Our results confirmed that CMS and venlafaxine modulate the expression levels and methylation status of genes involved in the TRYCATs pathway.
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