Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types...Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.展开更多
Objective: Heart failure(HF), a worldwide health condition, is the result of many cardiovascular diseases.The traditional Chinese medicine(TCM) Xiaoyu Jiangzhi capsule(XYC) has long been in use in China to treat hyper...Objective: Heart failure(HF), a worldwide health condition, is the result of many cardiovascular diseases.The traditional Chinese medicine(TCM) Xiaoyu Jiangzhi capsule(XYC) has long been in use in China to treat hyperlipidemia and inhibit platelet aggregation. This study explores the effects of XYC on heart failure(HF) and its detailed mechanisms.Methods: Isoproterenol(ISO, 30 mg/kg) was injected intraperitoneally for 7 days to copy a HF model of 10-12 weeks old, 20-30 g male mice. We then compared the CON(control) group, ISO(HF model)group, MET(metoprolol) group, and XYC group. Cardiac systolic function and left wall thickness were evaluated by echocardiograph. Using western blot analysis, we detected the proteins of calmodulin dependent protein kinase Ⅱ(Ca MKII) and sarco/endoplasmic reticulum Ca^(2+)-ATPase(Serca). Furthermore, ts A201 cells were cultured and the human CaV1.2 calcium channel current(hCaV1.2) were detected by patch clamp experiments.Results: XYC reduced HF, inhibiting the protein expression of Ca MKII, but Serca did not change significantly. Moreover, XYC inhibited the peak amplitude of the hCaV1.2 current, depolarizing shifted the activation curve 27.6 mV, and shifted the inactivation curve toward a positive potential 17.6 mV. The fraction recovered from inaction was reduced in XYC group compared with that in CON group.Conclusion: XYC could inhibit ISO-induced HF by reducing the Ca^(2+)/Ca MKII signaling pathway in mice.展开更多
目的:研究柴胡疏肝汤对氯化锂-匹罗卡品所致的慢性颞叶癫痫模型大鼠NMDA(N-methylD-aspartate)受体亚单位NR2B和钙调蛋白依赖性蛋白激酶Ⅱ(Calcium/Calmodulin-dependent Protein KinaseⅡ,CaMKII)表达及行为学的影响。方法:将50只制备...目的:研究柴胡疏肝汤对氯化锂-匹罗卡品所致的慢性颞叶癫痫模型大鼠NMDA(N-methylD-aspartate)受体亚单位NR2B和钙调蛋白依赖性蛋白激酶Ⅱ(Calcium/Calmodulin-dependent Protein KinaseⅡ,CaMKII)表达及行为学的影响。方法:将50只制备成功的Wistar慢性颞叶癫痫大鼠(B)随机分为5组(B_(1-5)),艾芬地尔组(B_2)予艾芬地尔(ifenprodil)10 mg·kg^(-1)腹腔注射,柴胡疏肝汤低、中、高剂量组(B_(3-5))分别予柴胡疏肝汤2.5,5,10 g·kg^(-1)灌胃,空白对照组(A)和生理盐水组(B_1)均予等容积生理盐水腹腔注射,各组连续干预8周,同时进行行为学视频监测,8周后运用免疫组织化学和western blot检测各组大鼠海马、颞叶皮层NR2B和CaMKII的表达情况。结果:艾芬地尔组和柴胡疏肝汤高剂量组大鼠的发作次数较模型组明显降低(P<0.05);在大鼠海马、颞叶皮层,与空白对照组相比,模型组NR2B和CaMKII的表达水平明显增高(P<0.05);与模型组相比,艾芬地尔组及柴胡疏肝汤高剂量组NR2B和CaMKII的表达水平降低(P<0.05);艾芬地尔组与柴胡疏肝汤高剂量组的表达无明显差异(P>0.05)。结论:柴胡疏肝汤高剂量可减少慢性颞叶癫痫大鼠痫性发作次数,且具有抑制NR2B及CaMKII的作用,这可能是柴胡疏肝汤发挥其抗癫痫作用的机制之一。展开更多
基金supported by the STI 2030—Major Projects 2021ZD0204000,No.2021ZD0204003 (to XZ)the National Natural Science Foundation of China,Nos.32170973 (to XZ),32071018 (to ZH)。
文摘Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.
基金supported by the National Natural Science Foundation of Guangdong (2020A1515010777)the Fund of Chinese Medicine Bureau of Guangdong Province (20201142)。
文摘Objective: Heart failure(HF), a worldwide health condition, is the result of many cardiovascular diseases.The traditional Chinese medicine(TCM) Xiaoyu Jiangzhi capsule(XYC) has long been in use in China to treat hyperlipidemia and inhibit platelet aggregation. This study explores the effects of XYC on heart failure(HF) and its detailed mechanisms.Methods: Isoproterenol(ISO, 30 mg/kg) was injected intraperitoneally for 7 days to copy a HF model of 10-12 weeks old, 20-30 g male mice. We then compared the CON(control) group, ISO(HF model)group, MET(metoprolol) group, and XYC group. Cardiac systolic function and left wall thickness were evaluated by echocardiograph. Using western blot analysis, we detected the proteins of calmodulin dependent protein kinase Ⅱ(Ca MKII) and sarco/endoplasmic reticulum Ca^(2+)-ATPase(Serca). Furthermore, ts A201 cells were cultured and the human CaV1.2 calcium channel current(hCaV1.2) were detected by patch clamp experiments.Results: XYC reduced HF, inhibiting the protein expression of Ca MKII, but Serca did not change significantly. Moreover, XYC inhibited the peak amplitude of the hCaV1.2 current, depolarizing shifted the activation curve 27.6 mV, and shifted the inactivation curve toward a positive potential 17.6 mV. The fraction recovered from inaction was reduced in XYC group compared with that in CON group.Conclusion: XYC could inhibit ISO-induced HF by reducing the Ca^(2+)/Ca MKII signaling pathway in mice.
