Effect of Jian-Pi-Zhi-Dong Decoction on the Amino Acid Neurotransmitters in a Rat Model of Tourette Syndrome and Comorbid Anxiety Disorder

Zhang, Wen; Yu, Wenjing; Liu, Xiaofang; Wang, Qian; Bai, Xue; Cui, Xia; Wang, Sumei

doi:10.3389/fpsyt.2020.00515

Cited by 3 publications

(3 citation statements)

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“…Moreover, it has been shown that the levels of NMDAR in the cortex and striatum decreases in rats with TS, but can be increased with treatment of Jian-Pi-Zhi-Dong decoction (Zhang et al. 2020 ). Similarly, we found that NMDAR level decreased in both the striatum and BV2 cells in the TS model group; however, after the treatment with JA, NMDAR level increased significantly and became higher than in the model group, both in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

Jing-an oral liquid alleviates Tourette syndrome via the NMDAR/MAPK/CREB pathway in vivo and in vitro

et al. 2022

Pharmaceutical Biology

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Context Jing-an oral liquid (JA) is a Chinese herbal formula used in the treatment of Tourette syndrome (TS); however, its mechanism is unclear. Objective To investigate the effects of JA on amino acid neurotransmitters and microglia activation in vivo and in vitro . Materials and methods Sixty male Sprague–Dawley rats were divided into a control group and 5 TS groups. TS was induced in rats with intraperitoneal injection of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1 mg/kg) and in BV2 cells with lipopolysaccharide. Control and model rats were administered saline, whereas treatment groups were administered JA (5.18, 10.36, or 20.72 g/kg) or tiapride (a benzamide, 23.5 mg/kg) by gavage once daily for 21 days. Stereotypic behaviour was tested. The levels of N -methyl- d -aspartate receptor (NMDAR)/mitogen-activated protein kinase/cAMP response element-binding protein (CREB)-related proteins in striatum and BV2 cells were measured via western blots. CD11b and IBa1 levels were also measured. Ultra-high-performance liquid-chromatography was used to determine γ-aminobutyric acid (GABA), glutamic acid (Glu), and aspartic acid (ASP) levels. Results JA markedly alleviated the stereotype behaviour (25.92 ± 0.35 to 13.78 ± 0.47) in rats. It also increased NMDAR1 (0.48 ± 0.09 to 0.67 ± 0.08; 0.54 ± 0.07 to 1.19 ± 0.18) expression and down-regulated the expression of p-ERK, p-JNK, p-P38, and p-CREB in BV2 cells and rat striatum. Additionally, Glu, ASP, GABA, CD11b, and IBa1 levels were significantly decreased by JA. Discussion and conclusions JA suppressed microglia activation and regulated the levels of amino acid neurotransmitters, indicating that it could be a promising therapeutic agent for TS.

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Section: Discussionmentioning

confidence: 99%

Jing-an oral liquid alleviates Tourette syndrome via the NMDAR/MAPK/CREB pathway in vivo and in vitro

et al. 2022

Pharmaceutical Biology

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“…At present, the etiology of GAD is unclear, but it is certain that environmental pressure is an important reason for its onset, repeated fluctuation, and deterioration ( Wittchen et al, 2000 ). Based on this, this study used the uncertain empty bottle drinking water stimulation method ( Lin Wenjuan, 2003 ; Zhang et al, 2020 ) and chronic restraint stress ( Ma et al, 2019 ) preparation of the GAD rat model. After 21 days of chronic stress stimulation, we found that GAD rats showed significant changes compared with the control group, such as decreased body weight growth rate ( Morris, 2019 ), reduced exploration behavior in the central area of the open field experiment ( Deacon, 2013 ), and significantly reduced exploration time to the open arm in the elevated cross maze ( Gasnas, 2021 ), and there were statistical differences, which proved that the physiological metabolism of the model group was disordered.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, there was anxiety of decreased desire for exploration and fear and timidity, which was consistent with the behavioral performance of anxiety disorder rats prepared by Wenjuan Lin ( Lin Wenjuan, 2003 ) and Shuichi Chiba ( Chiba et al, 2012 ). In addition, during the modeling period, the rats in the model group showed characteristics of depressed expression, easy frightening, dark yellow hair color, loss of luster, curling up in corners, and loose stool ( Zhang et al, 2020 ). It can be seen from the above that the GAD model prepared in our study is accurate and reliable, and the characterization is consistent with clinical symptoms ( Luyten et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Danzhi Xiaoyao Powder Promotes Neuronal Regeneration by Downregulating Notch Signaling Pathway in the Treatment of Generalized Anxiety Disorder

Liu

Ying

et al. 2021

Front. Pharmacol.

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Background: Generalized anxiety disorder (GAD) is one of the most common types of anxiety disorders with unclear pathogenesis. Our team’s previous research found that extensive neuronal apoptosis and neuronal regeneration disorders occur in the hippocampus of GAD rats. Danzhi Xiaoyao (DZXYS) Powder can improve the anxiety behavior of rats, but its molecular mechanism is not well understood.Objective: This paper discusses whether the pathogenesis of GAD is related to the abnormal expression of Notch signal pathway, and whether the anti-anxiety effect of DZXYS promotes nerve regeneration in the hippocampus by regulating the Notch signaling pathway.Methods: The animal model of GAD was developed by the chronic restraint stress and uncertain empty bottle stimulation method. After the model was successfully established, the rats in the model preparation group were divided into the buspirone, DZXYS, DZXYS + DAPT, and model groups, and were administered the corresponding drug intervention. The changes in body weight and food intake of rats were continuously monitored throughout the process. The changes in anxiety behavior of rats were measured by open field experiment and elevated plus-maze test, and morphological changes and regeneration of neurons in the rat hippocampus were observed by HE staining and double immunofluorescence staining. Changes in the expression of key targets of the Notch signaling pathway in the hippocampus were monitored by real-time fluorescence quantitative PCR and western blotting.Results: In this study, we verified that the GAD model was stable and reliable, and found that the key targets of the Notch signaling pathway (Notch1, Hes1, Hes5, etc.) in the hippocampus of GAD rats were significantly upregulated, leading to the increased proliferation of neural stem cells in the hippocampus and increased differentiation into astrocytes, resulting in neuronal regeneration. DZXYS intervention in GAD rats can improve appetite, promote weight growth, and significantly reverse the anxiety behavior of GAD rats, which can inhibit the upregulation of key targets of the Notch signaling pathway, promote the differentiation of neural stem cells in the hippocampus into neurons, and inhibit their differentiation into astrocytes, thus alleviating anxiety behavior.Conclusion: The occurrence of GAD is closely related to the upregulation of the Notch signaling pathway, which hinders the regeneration of normal neurons in the hippocampus, while DZXYS can downregulate the Notch signaling pathway and promote neuronal regeneration in the hippocampus, thereby relieving anxiety behavior.

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New insights of metabolite abnormalities in the thalamus of rats with iminodiproprionitrile-induced tic disorders

Yu,

Yao,

Zhang

et al. 2023

Front. Neurosci.

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IntroductionThis study aimed to investigate pathological changes in the “Glutamate (Glu)-γ-aminobutyric acid (GABA)” loop and apply widely targeted metabolomic analysis technology to comprehensively explore metabolite abnormalities/ in the thalamus of rats with tic disorders (TD).MethodsWistar rats were randomized into control, TD, and tiapride (Tia) groups. Iminodipropionitrile (IDPN) was used to induce TD in rats. The Tia group was administered tiapride. Neurotransmitter levels in the thalamus of rats in the three groups were measured using UPLC-3Q MS. And, the protein expression levels of Glu decarboxylase (GAD65/67) and GABA transporter protein (GAD-T) were measured using western blotting. The mRNA expression levels of these genes were evaluated using real-time polymerase chain reaction. Lastly, other metabolites in the thalamus were detected by widely targeted metabolomic analysis between TD and Control group rats.ResultsThe Glu level, Glu/GABA ratio, and Asp level in the TD group were significantly higher (all p < 0.001) than those of the Control group, whereas the GABA and Gly levels were lower (p < 0.001 and p = 0.009, respectively). The Tia group exhibited a significant reduction in the Glu level (p = 0.001) compared with the TD group. The protein expression level of GAD67 in TD group was higher (p = 0.009) and the mRNA expression levels of GAD65, GAD67, and GAT-1 were lower (p < 0.05) than those of the Control group. The Tia group did not display any differences in GAD65, GAD67, or GAT-1 expression. Widely targeted metabolomic analysis revealed that 34 substances were abnornal between the TD and Control groups (9 upregulated and 25 downregulated). Neurosteroids (progesterone, corticosterone) exhibited distinct differences. Metabolite analysis using the Kyoto encyclopedia for genes and genomes indicated that the steroid hormone biosynthesis pathway may be involved in TD pathogenesis.ConclusionThis study revealed metabolic abnormalities in the thalamus of rats with TD. The interaction between neurotransmitters and neurosteroid biosynthesis represents a new direction for future studies.

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Effect of Jian-Pi-Zhi-Dong Decoction on the Amino Acid Neurotransmitters in a Rat Model of Tourette Syndrome and Comorbid Anxiety Disorder

Cited by 3 publications

References 43 publications

Jing-an oral liquid alleviates Tourette syndrome via the NMDAR/MAPK/CREB pathway in vivo and in vitro

Jing-an oral liquid alleviates Tourette syndrome via the NMDAR/MAPK/CREB pathway in vivo and in vitro

Danzhi Xiaoyao Powder Promotes Neuronal Regeneration by Downregulating Notch Signaling Pathway in the Treatment of Generalized Anxiety Disorder

New insights of metabolite abnormalities in the thalamus of rats with iminodiproprionitrile-induced tic disorders

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