Research progress on susceptibility genes in children with tic disorder / 中华实用儿科临床杂志

Tic disorder (TD) is a neurodevelopmental disorder that starts in childhood with tics as its primary clinical manifestation.It is a group of movement disorders with unknown causes.At present, the main pathogenic genes of TD have not been identified.In this paper, TD neurotransmitter-associated susceptibility genes ( DRD2, DRD4, SLC6A4, HDC, ADRA2A), related susceptibility gene variations ( ASH1L, CELSR3, PNKD, NRXN1, CNTN6), and other susceptibility genes ( FLT3, SLITRK1) were reviewed to provide references for the precision treatment based on gene variations.

Research progress on endogenous small-molecule phenolics and the proposal of "phenolomics" / 药学学报

Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.

Anmeidan Regulates Hepatic Neurotransmitters and Circadian Rhythm in Rat Model of Insomnia via OX1R/PLCβ-1/PKCα/ERK1/2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect and mechanism of the classic famous prescription Anmeidan （AMD） developed in the Qing Dynasty in regulating the hepatic neurotransmitters and circadian rhythm in the rat model of insomnia via the orexin-1 receptor （OX1R）/phosphatidylinositol-specific phospholipase Cβ-1 （PLCβ-1）/protein kinase Cα （PKCα）/extracellular signal-regulated kinase 1/2 （ERK1/2） signaling pathway. MethodSixty SPF-grade SD rats were randomized into blank， model， suvorexant （30 mg·kg-1·d-1）， and low-， medium-， and high-dose （4.55， 9.09， 18.09 g·kg-1·d-1， respectively） AMD groups， with 10 rats in each group. The rats in other groups except the blank group were modeled by intraperitoneal injection of p-chlorophenylalanine （PCPA） and administrated with corresponding drugs by gavage， and the blank group received an equal volume of normal saline. The general condition， body mass， and 24 h autonomic activity of each group were observed. The pathological changes of the liver tissue were observed by hematoxylin-eosin（HE）staining and Masson staining. The expression of gamma-aminobutyric acid （GABA）， 5-hydroxytryptamine （5-HT）， epinephrine （EPI）， norepinephrine （NE）， and acetylcholine （ACh） in the liver tissue was detected by enzyme-linked immunosorbent assay. The glutamate （Glu） expression in the liver tissue was detected by the biochemical method. The mRNA levels of biological clock genes Per1， Per2， Cry1， Cry2， Bmal1， and Bmal2 in the liver were determined by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. The protein and mRNA levels of factors in the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway in the liver were determined by Western blot and Real-time PCR， respectively. ResultCompared with the blank group， the modeling decreased the body mass （P<0.05， P<0.01） and caused mania and disturbed resting rhythms （P<0.01）， hepatic muscle fiber fracture， and edema with inflammatory cell infiltration. In addition， the modeling decreased the GABA， 5-HT， EPI， NE， and ACh content， increased Glu content （P<0.01）， down-regulated the mRNA levels of Per1， Per2， Cry1， and Cry2 （P<0.01）， up-regulated the mRNA levels of Bmal1 and Bmal2 （P<0.01）， and promoted the expression of OX1R， PLCβ-1， PKCα， and ERK1/2 at both protein and mRNA levels （P<0.01）. Compared with the model group， suvorexant and AMD increased the body mass （P<0.05， P<0.01）， alleviated the mania， and increased the resting time and frequency （P<0.05， P<0.01）. Moreover， the medications elevated the levels of GABA， 5-HT， EPI， NE， and ACh， lowered the Glu level， up-regulated the mRNA levels of Per1， Per2， Cry1， and Cry2 （P<0.05， P<0.01）， down-regulated the mRNA levels of Bmal1 and Bmal2， and inhibited the expression of OX1R， PLCβ-1， PKCα， and ERK1/2 at both mRNA and protein levels （P<0.05， P<0.01）. ConclusionAMD can regulate hepatic neurotransmitters and improve circadian rhythm in insomniac rats by inhibiting the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway， and high-dose AMD demonstrated the strongest effect.

Distribution of calcitonin gene-related peptide and vascular endothelial growth factor in the mouse lung at the embryonic and postnatal stages / Distribución del péptido relacionado con el gen de la calcitonina y el factor de crecimiento endotelial vascular en el pulmón de ratón en las etapas embrionaria y posnatal

SUMMARY: Neuropeptide calcitonin gene-related peptide (CGRP) is a neurotransmitter related to vasculogenesis during organ development. The vascular endothelial growth factor A (VEGF-A) is also required for vascular patterning during lung morphogenesis. CGRP is primarily found in organs and initially appears in pulmonary neuroendocrine cells during the early embryonic stage of lung development. However, the relationship between CGRP and VEGF-A during lung formation remains unclear. This study investigates CGRP and VEGF-A mRNA expressions in the embryonic, pseudoglandular, canalicular, saccular, and alveolar stages of lung development from embryonic day 12.5 (E12.5) to postnatal day 5 (P5) through quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. Further, we analyzed the expression of CGRP via immunohistochemistry. The VEGF-A mRNA was mainly scattered across the whole lung body from E12.5. CGRP was found to be expressed in a few epithelial cells of the canalicular and the respiratory bronchiole of the lung from E12.5 to P5. An antisense probe for CGRP mRNA was strongly detected in the lung from E14.5 to E17.5. Endogenous CGRP may regulate the development of the embryonic alveoli from E14.5 to E17.5 in a temporal manner.

El péptido relacionado con el gen de la calcitonina (CGRP) es un neurotransmisor vinculado con la vasculogénesis durante el desarrollo de órganos. El factor de crecimiento endotelial vascular A (VEGF-A) también se requiere para el patrón vascular durante la morfogénesis pulmonar. El CGRP se encuentra principalmente en los órganos y aparece inicialmente en las células neuroendocrinas pulmonares durante la etapa embrionaria temprana del desarrollo pulmonar. Sin embargo, la relación entre CGRP y VEGF-A durante la formación de los pulmones sigue sin estar clara. Este estudio investiga las expresiones de ARNm de CGRP y VEGF-A en las etapas embrionaria, pseudoglandular, canalicular, sacular y alveolar del desarrollo pulmonar desde el día embrionario 12,5 (E12,5) hasta el día postnatal 5 (P5) a través de la reacción en cadena de la polimerasa cuantitativa en tiempo real. (qRT-PCR) e hibridación in situ. Además, analizamos la expresión de CGRP mediante inmunohistoquímica. El ARNm de VEGF-A se dispersó principalmente por todo parénquima pulmonar desde E12,5. Se encontró que CGRP se expresaba en unas pocas células epiteliales de los bronquiolos canaliculares y respiratorios del pulmón desde E12,5 a P5. Se detectó fuertemente una sonda antisentido para ARNm de CGRP en el pulmón de E14,5 a E17,5. El CGRP endógeno puede regular el desarrollo de los alvéolos embrionarios de E14,5 a E17,5 de manera temporal.

Inhalation of Cananga odorata essential oil relieves anxiety behaviors in autism-like rats via regulation of serotonin and dopamine metabolism / 中西医结合学报

OBJECTIVE@#Anxiety is one of the most common symptoms associated with autistic spectrum disorder. The essential oil of Cananga odorata (Lam.) Hook. f. & Thomson, usually known as ylang-ylang oil (YYO), is often used in aromatherapy as a mood-regulating agent, sedative, or hypotensive agent. In the present study, the effects and mechanisms of YYO in alleviating anxiety, social and cognitive behaviors in autism-like rats were investigated.@*METHODS@#The prenatal valproic acid (VPA) model was used to induce autism-like behaviors in offspring rats. The effectiveness of prenatal sodium valproate treatment (600 mg/kg) on offspring was shown by postnatal growth observation, and negative geotaxis, olfactory discrimination and Morris water maze (MWM) tests. Then three treatment groups were formed with varying exposure to atomized YYO to explore the effects of YYO on the anxiety, social and cognitive behaviors of the autistic-like offspring through the elevated plus-maze test, three-chamber social test, and MWM test. Finally, the monoamine neurotransmitters, including serotonin, dopamine and their metabolites, in the hippocampus and prefrontal cortex (PFC) of the rats were measured using a high-performance liquid chromatography.@*RESULTS@#Offspring of VPA exposure rats showed autism-like behaviors. In the VPA offspring, medium-dose YYO exposure significantly elevated the time and entries into the open arms in the elevated plus-maze test, while low-dose YYO exposure significantly enhanced the social interaction time with the stranger rat in session 1 of the three-chamber social test. VPA offspring treated with YYO exposure used less time to reach the platform in the navigation test of the MWM test. YYO exposure significantly elevated the metabolism of serotonin and dopamine in the PFC of VPA offspring.@*CONCLUSION@#YYO exposure showed the effects in alleviating anxiety and improving cognitive and social abilities in the offspring of VPA exposure rats. The role of YYO was related to the regulation of the metabolism of serotonin and dopamine. Please cite this article as: Zhang N, Wang ST, Yao L. Inhalation of Cananga odorata essential oil relieves anxiety behaviors in autism-like rats via regulation of serotonin and dopamine metabolism. J Integr Med. 2023; 21(2): 205-214.

Effects of different acupuncture schemes on neurotransmitters and related inflammatory factors in rats with post-stroke depression / 中国康复理论与实践

ObjectiveTo investigate the effects of different acupuncture schemes on behaviors, neurotransmitters and inflammation-related factors in post-stroke depressed (PSD) rats. MethodsA total of 72 healthy male Sprague-Dawley rats were randomly divided into normal group, model group, drug control group, scalp acupuncture group, abdominal acupuncture group and combined acupuncture group, 12 rats in each group. The PSD model was prepared using a combination of middle cerebral artery occlusion and chronic unpredictable mild stimulation (CUMS) for the model and each intervention groups. The drug control group was administered fluoxetine, the scalp acupuncture group accepted acupuncture at Baihui (DU 20) and Yintang (EX-HN3), while the abdominal acupuncture group at Zhongwan (RN 12) and Guanyuan (RN 4), the combined acupuncture group at all the four acupoints, for 21 days. They were assessed with Longa neurological function score, body mass, open-field test and sugar-water preference test on the 0 (before modeling), the seventh (before CUMS), the 14th (before treatment) and the 35th day (after treatment). The levels of 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), interferon-γ (INF-γ), tumor necrosis factor⁃α (TNF⁃α) and macrophage migration inhibitory factor (MIF) in the serum were determined with ELISA on the 35th day. Results The neurological function score was lower in the drug control group and the combined acupuncture group thanin the model group (P < 0.01) on the 35th day; while the body mass was higher in the drug control group, the abdominal acupuncture group and the combined acupuncture group than in the model group (P < 0.01); and the number of horizontal span frames, the number of uprightness and the sugar water consumption were higher in the drug control group, the scalp acupuncture group, the abdominal acupuncture group and the combined acupuncture group than in the model group (P < 0.05). There was no significant difference among the four intervention groups (P > 0.05). The levels of 5-HT, DA and NE were higher in the four intervention groups than in the model group (P < 0.01), and the levels of IFN-γ, TNF⁃α and MIF were lower (P < 0.01). 5-HT level was higher in the combined acupuncture group than in the scalp acupuncture group and the abdominal acupuncture group, and the levels of IFN-γ, TNF⁃α and MIF were lower (P < 0.01); the levels of DA and NE was higher in the combined acupuncture group than in the abdominal acupuncture group (P < 0.01). ConclusionThe combination of scalp acupuncture and abdominal acupuncture can improve behavior, neurotransmitters and inflammatory factors of PSD rats, like fluoxetine. Scalp or abdominal acupuncture alone is still effecive, and can be used secondarily.

Effects of moxa smoke through olfactory pathway on learning and memory ability in rapid aging mice / 中国针灸

OBJECTIVE@#To observe the effects of moxa smoke through olfactory pathway on learning and memory ability in rapid aging (SAMP8) mice, and to explore the action pathway of moxa smoke.@*METHODS@#Forty-eight six-month-old male SAMP8 mice were randomly divided into a model group, an olfactory dysfunction group, a moxa smoke group and an olfactory dysfunction + moxa smoke group, with 12 mice in each group. Twelve age-matched male SAMR1 mice were used as the blank group. The olfactory dysfunction model was induced in the olfactory dysfunction group and the olfactory dysfunction + moxa smoke group by intraperitoneal injection of 3-methylindole (3-MI) with 300 mg/kg, and the moxa smoke group and the olfactory dysfunction + moxa smoke group were intervened with moxa smoke at a concentration of 10-15 mg/m3 for 30 min per day, with a total of 6 interventions per week. After 6 weeks, the emotion and cognitive function of mice was tested by open field test and Morris water maze test, and the neuronal morphology in the CAI area of the hippocampus was observed by HE staining. The contents of neurotransmitters (glutamic acid [Glu], gamma-aminobutyric acid [GABA], dopamine [DA], and 5-hydroxytryptamine [5-HT]) in hippocampal tissue of mice were detected by ELISA.@*RESULTS@#The mice in the blank group, the model group and the moxa smoke group could find the buried food pellets within 300 s, while the mice in the olfactory dysfunction group and the olfactory dysfunction + moxa smoke group took more than 300 s to find them. Compared with the blank group, the model group had increased vertical and horizontal movements (P<0.05) and reduced central area residence time (P<0.05) in the open field test, prolonged mean escape latency on days 1-4 (P<0.05), and decreased search time, swimming distance and swimming distance ratio in the target quadrant of the Morris water maze test, and decreased GABA, DA and 5-HT contents (P<0.05, P<0.01) and increased Glu content (P<0.05) in hippocampal tissue. Compared with the model group, the olfactory dysfunction group had increased vertical movements (P<0.05), reduced central area residence time (P<0.05), and increased DA content in hippocampal tissue (P<0.05); the olfactory dysfunction + moxa smoke group had shortened mean escape latency on days 3 and 4 of the Morris water maze test (P<0.05) and increased DA content in hippocampal tissue (P<0.05); the moxa smoke group had prolonged search time in the target quadrant (P<0.05) and increased swimming distance ratio, and increased DA and 5-HT contents in hippocampal tissue (P<0.05, P<0.01) and decreased Glu content in hippocampal tissue (P<0.05). Compared with the olfactory dysfunction group, the olfactory dysfunction + moxa smoke group showed a shortened mean escape latency on day 4 of the Morris water maze test (P<0.05). Compared with the moxa smoke group, the olfactory dysfunction + moxa smoke group had a decreased 5-HT content in the hippocampus (P<0.05). Compared with the blank group, the model group showed a reduced number of neurons in the CA1 area of the hippocampus with a disordered arrangement; the olfactory dysfunction group had similar neuronal morphology in the CA1 area of the hippocampus to the model group. Compared with the model group, the moxa smoke group had an increased number of neurons in the CA1 area of the hippocampus that were more densely packed. Compared with the moxa smoke group, the olfactory dysfunction + moxa smoke group had a reduced number of neurons in the CA1 area of the hippocampus, with the extent between that of the moxa smoke group and the olfactory dysfunction group.@*CONCLUSION@#The moxa smoke could regulate the contents of neurotransmitters Glu, DA and 5-HT in hippocampal tissue through olfactory pathway to improve the learning and memory ability of SAMP8 mice, and the olfactory is not the only effective pathway.

Effects of Wenyang jieyu decoction on PI3K/Akt signaling pathway and neurotransmitters in kidney-yang deficiency depressed rats / 中国药房

OBJECTIVE To investigate the effects of Wenyang jieyu decoction on phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and neurotransmitters in rats with kidney-yang deficiency depression. METHODS The SD rats were divided into blank group， model group， fluoxetine group （positive control of western medicine， 4.17 mg/kg）， Xiaoyao powder group （positive control of TCM， 1.88 g/kg） and Wenyang jieyu decoction low-dose， medium-dose and high-dose groups （1.25， 2.50， 5.00 g/kg）， with 15 rats in each group. Except for blank group， the other groups were treated with corticosterone 20 mg/kg subcutaneously to induce kidney-yang deficiency depressed model， meanwhile the mice were given relevant medicine intragastrically， once a day， for 28 consecutive days. The general conditions of rats were observed. The sucrose preference rate and the static time of forced swimming were detected， and organ indexes of rats were calculated. The levels/contents of neurotransmitters in serum were detected， the expressions of PI3K/Akt pathway-related proteins in hippocampus were detected， and the number of dendritic spines was determined. RESULTS Compared with blank group， model group suffered from the symptoms such as hair loss， fear of cold， curling up； sucrose preference rate， indexes of adrenal gland， thymus gland and spleen，serum levels of cyclic adenosine phosphate （cAMP）， brain-derived neurotrophic factor and gamma-aminobutyric acid， the ratio of cAMP to cyclic guanosine monophosphate， the contents of norepinephrine， dopamine and 5-hydroxy-tryptamine， the expressions of PI3K， Akt， mammalian target of rapamycin， and the number of dendritic spines in the hippocampus were significantly decreased （P＜0.01）. The time of immobility， level of glutamic acid and protein expression of glycogen synthetase kinase-3β were prolonged and increased （P＜0.01）. Compared with model group， depression symptoms of rats in each administration group were improved， and the above indexes were mostly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS Wenyang jieyu decoction can improve depression-like behavior and the deficiency of kidney-yang， regulate the secretion of neurotransmitters， and activate PI3K/Akt signaling pathway， thus playing a role in protecting hippocampal neurons.

Functional Autapses Form in Striatal Parvalbumin Interneurons but not Medium Spiny Projection Neurons / 神经科学通报·英文版

Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr2+. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABAA receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions.

Effects of Paroxetine and Sulpiride in the Treatment of Social Phobia in Young Women and Its Effects on Neurotransmitter and Sleep Structure / 昆明医科大学学报

Objective To explore the effects of paroxetine and sulpiride in the treatment of social phobia in young women and the effects on neurotransmitters and sleep structure.Methods 102 young female patients with social phobia in our hospital from February 2021 to February 2023 were selected and divided into 2 groups with 51 cases in each group by random number table method.The control group was treated with Paxil,and the study group was treated with Paxil + sulpiride for 3 months.Treatment effect,neurotransmitters[5-hydroxytryptamine(5-HT),dopamine(DA),gamma-aminobutyric acid(GABA),myeloperoxidase(MPO)],sleep structure,social anxiety(LASA),social fear(SPS)and social Results The research group's overall effective rate of treatment is 88.24%,which is higher than the control group's 70.59%(P<0.05).1 month and 3 months after treatment,the research group's serum levels of DA and MPO are lower than those of the control group,while the levels of 5-HT and GABA are higher than those of the control group(P<0.05).1 month and 3 months after treatment,the research group's sleep transition frequency and the proportion of stage Ⅰ + stage Ⅱ are lower than those of the control group,while the proportion of stage Ⅲ + stage Ⅳ and REM stage are higher than those of the control group(P<0.05).1 month and 3 months after treatment,the research group's LASA,SPS,and SAFE scores are lower than those of the control group(P<0.05);The incidence of adverse events in the research group is 13.73%compared to 9.80%in the control group,with no statistically significant difference(P>0.05).Conclusion Paroxetine and sulpiride combined can improve the sleep structure of young women with social phobia,regulate serum neurotransmitter levels,alleviate social anxiety symptoms,improve social adaptability,and have a certain level of safety.

Pharmacodynamics Combined with Network Pharmacology to Study the Intervention Effect of Suanzaoren Decoction on Different Disease Models and its Mechanism / 世界科学技术-中医药现代化

Objective To investigate the intervention effect and mechanism of Suanzaoren decoction(SZRD)on insomnia and depression model mice based on pharmacodynamics and network pharmacology.Methods According to the insomnia disease model,the mice were randomly divided into control,insomnia model,SZRD low-dose,high-dose and diazepam groups;according to the depression disease model,the mice were randomly divided into control,depression model,SZRD low-dose,high-dose and Xiaoyao pill groups.The contents of 5-hydroxytryptamine(5-HT),norepinephrine(NE),and dopamine(DA)in the brains of mice were measured on days 7 and 28,and behavioral evaluations were performed in each group of mice.With the help of network pharmacology method to predict the key targets and related pathways of Suanzaoren decoction in the treatment of insomnia and depression,and to explore its mechanism.Results Behavioral tests and neurotransmitter content determination showed that SZRD could prolong sleep time(P<0.05),improve insomnia behavioral performance in model mice(P<0.05),reduce NE and DA contents in brain tissue of insomnia mice,increase 5-HT content(P<0.05),and was more significant in the low-dose group(P<0.05);SZRD could improve depression behavioral performance,increase sugar water preference,and reduce immobility time in model mice(P<0.05,P<0.01),and increase NE,DA,and 5-HT contents in brain tissue of depression mice(P<0.05),and was more significant in the high-dose group(P<0.05).18 core targets of SZRD in the treatment of insomnia and 34 core targets in the treatment of depression were predicted with the help of network pharmacology methods,and gene ontology(GO)functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that SZRD mainly involved biological processes such as dopamine neurotransmitter receptor activity,synaptic transmission and cellular response to reactive oxygen species,and acted on pathways such as the cGMP-PKG signaling pathway and IL-17 signaling pathway to exert therapeutic effects.Conclusion The changes of NE,DA and 5-HT contents in insomnia and depression model mice are not consistent,and the intervention effect of Suanzaoren decoction is also different.Low and high doses of Suanzaoren decoction can exert the best therapeutic effect on insomnia and depression model mice,respectively,and its promoting sleep and antidepressant effects may be related to the cGMP-PKG signaling pathway and IL-17 signaling pathway.

Effects of warming-yang and tonifying-qi needling combined with electromyographic biofeedback on brain image structure,surface myoelectric characteristics and neurotransmitters in patients undergoing stroke rehabilitation / 中国中西医结合急救杂志

Objective To explore the effects of warming-yang and tonifying-qi needling combined with electromyographic biofeedback therapy(EMGBFT)on brain image structure,surface myoelectric characteristics and neurotransmitters in patients with stroke rehabilitation.Methods A prospective research method was conducted in which 200 stroke rehabilitation patients admitted to the Third Hospital of Xingtai City from February 2021 to February 2022 were selected as the study subjects.According to the random principle,the patients were divided into a control group and an study group,with 100 cases in each group.Both groups received routine treatment for stroke,while the control group received a combination of EMGBFT.The study group received a combination of warming-yang and tonifying-qi acupuncture based on the control group,and both groups continued to receive treatment for 9 weeks.Observe the clinical efficacy of two groups of patients and compare the differences in National Institutes of Health Stroke Scale(NIHSS)scores,traditional Chinese medicine symptom scores,brain image structures,serum neurotransmitter levels,and surface electromyography levels before and after treatment,and observe the occurrence of adverse reactions.Results The effective rate of treatment in the study group was significantly higher than that in the control group(97.00％ vs.87.00％,P<0.05).After treatment,NIHSS score,traditional Chinese medicine symptom score,root-mean-square(RMS)of biceps and triceps,and synergistic contraction rate(SCR)were significantly lower than those before treatment in both groups,and the levels of cerebral blood flow(CBF)in the thalamus and frontal lobe,fractional anisotropy(FA),norepinephrine(NE),5-hydroxytryptamine(5-TH),and dopamine(DA)were significantly higher than those before treatment.After treatment,the NIHSS score(4.18±1.09 vs.6.89±1.54),traditional Chinese medicine symptom score(5.41±1.08 vs.9.46±1.55),and biceps RMS(μV:9.76±3.51 vs.16.36±3.44),triceps brachii RMS(μV:6.79±1.83 vs.10.61±2.87),and SCR[(28.08±8.73)％ vs.33.08±9.31)％]were significantly lower than those control group(all P<0.05),the CBF of the thalamus(mL·kg-1·min-1:278.97±86.32 vs.233.63±84.62),and the CBF of the frontal lobe(mL·kg-1·min-1:299.31±75.54 vs.262.81±87.18),FA(0.57±0.18 vs.0.48±0.14),serum 5-HT(ng/L:352.83±38.93 vs.306.71±32.54),NE(ng/L:160.83±17.25 vs.122.81±12.41),DA(μg/L:9.23±0.92 vs.7.36±0.71)were significantly higher than those of the control group(all P<0.05).The incidence of adverse reactions in the study group was significantly lower than that in the control group(3.00％ vs.14.00％,P<0.05).Conclusion Based on EMGBFT,the combination of warming-yang and tonifying-qi acupuncture can synergistically improve the clinical symptoms and brain image structure in stroke rehabilitation patients,and increase their serum neurotransmitter levels,with fewer adverse reactions,which is worthy of promotion.

Clinical features and laboratory characteristics of 4 cases of aromatic L-amino acid decarboxylase deficiency / 中华神经科杂志

Objective:To investigate the clinical characteristics, laboratory characteristics and genetic diagnosis of aromatic L-amino acid decarboxylase deficiency (AADCD), and to improve the understanding of this disease.Methods:Four children diagnosed with AADCD from the Department of Neurology, Beijing Children′s Hospital Affiliated to Capital Medical University from August 2016 to June 2020 were collected, and their clinical manifestations, laboratory and imaging data, and genetic test results were retrospectively analyzed.Results:All the 4 cases were diagnosed in early infancy, with the first symptom of feeding difficulties. They developed paroxysmal dyspraxia accompanied by eye movement crisis, movement regression, hypotonia, growth retardation, sleep disorders and autonomic nervous symptoms such as ptosis, excessive sweating and nasal congestion at the age of 2-4 months, respectively. The 4 children were siblings from 2 families with healthy parents. The dihydroxyphenylalanine decarboxylase ( DDC) gene mutations in cases 1 and 2 were derived from the maternal missense mutation c.1040G>A(P.RG347gln), and from the paternal deletion of exons 11 and 12, respectively. The DDC gene mutation in case 3 was derived from the maternal mutation c.419G>A(p.G140E) and the paternal mutation c.1375C>T(p.H459Y), respectively. Case 4 did not undergo genetic testing. Blood amino acid and acylcarnitine profiles and urine organic acid analyses were performed in 3 cases, and no specific abnormalities were found. In case 3, the results of 3-O-methyldopa (3-OMD) screening by blood dry filter paper increased significantly. Cerebrospinal fluid neurotransmitter detection results showed that the concentrations of 3-methoxy-4-hydroxyphenyldiol, vanillic acid and 5-hydroxyindoleacetic acid were significantly decreased, while the levels of 5-hydroxytryptophan and 3-OMD were increased in case 3. Blood aromatic L-amino acid decarboxylase (AADC) activity decreased significantly in case 3. Cranial magnetic resonance imaging (MRI) and electroencephalogram (EEG) examinations were performed in cases 1, 3, and 4, among which the cranial MRI in case 1 was normal, while the cranial MRI in cases 3 and 4 suggested that myelination was slightly backward. The EEG was normal in all the 3 cases. Cases 1 and 2 died of pneumonia and respiratory failure at the age of 1 year and 10 months. Case 3 was given clonazepam, benxel hydrochloride tablets and vitamin B6 tablets orally after diagnosis at the age of 4 months, and then treated with selegiline hydrochloride tablets and pramexol hydrochloride tablets. At the follow-up of 1 year and 6 months, the frequency of eye movement crisis and movement disorder was reduced, sleep was improved and autonomic nervous symptoms were alleviated, but there was no improvement in developmental delay. Case 4 was diagnosed with cerebral palsy and epilepsy, but failed various antiepileptic drugs and rehabilitation training, and died at the age of 10 due to heart failure and kidney failure. Conclusions:The clinical manifestations of AADCD are complicated and the misdiagnosis rate is high. Infants with early-onset hypotonia, developmental retardation, eye movement crisis, and movement disorders should be screened with dry filter paper as soon as possible for 3-OMD level, and suspicious cases should be diagnosed by cerebrospinal fluid neurotransmitter detection, plasma AADC activity determination, and gene examination. Early diagnosis of AADCD in children and gene mutation carriers can guide treatment and provide genetic counseling to reduce the incidence of the offspring.

Study on the protective effect of salidroside on memory impairment in mice under high altitude hypoxia / 中国药理学通报

Aim To explore the effect of salidroside on the learning and memory ability of mice under high altitude hypoxia. Methods Forty-eight C57BL/6J male mice were randomly divided into plain control group, plateau model group and salidroside group according to their body weight, with 16 mice in each group. The animals in each group were given prophylactic doses for three days and then rushed to a plateau with an altitude of 4 010 m. After one day of hypoxia exposure, Morris water maze was performed to test the learning and memory ability of mice; malondialdehyde(MDA), hydrogen peroxide(H

Effects of treadmill exercise on learning and memory of the vascular dementia rats and its mechanism / 解剖学报

Objective To observe the effects of 4-week low intensity treadmill exercise on the learning and memory, amino acid levels and the protein expression of protein kinase A ( PKA) , cyclic adenosine monophosphate response element binding protein( CREB) and brain-derived neurotrophic factor(BDNF) in the prefrontal cortex (PFC) of the vascular dementia (VD) rats. Methods Thirty-nine SD rats were randomly allocated to 3 groups, sham group (sham, n= 13) , vascular dementia group (VD, n= 13) and vascular dementia treaded with exercise group (VD + EX, n= 13). Chronic cerebral ischemia model in VD group and VD+EX group rats were established by permanent ligation of bilateral, then VD+EX group rats were submitted to 4-week low intensity treadmill exercise. After exercise, spatial learning and memory ability were evaluated by Moms water maze test ( MWM ) , glutamic ( Glu ) and gamma-aminobutyric acid (GABA) levels in the PFC were measured by high performance liquid chromatography( HPLC) ; the protein expression of PKA, CREB and BDNF in the PFC of rats were detected by Western blotting. Results The result of the MWM showed the average escape latency of rats in the VD group on the 1 -5 days was significantly higer than sham group, the time to first find the original platform was significantly prolonged and the platform crossings decreased significantly ( P 0. 05 ) between the two groups. Conclusion Four-week low-intensity running exercise improves the learning and memory ability of VD rats through enhancing the Glu level and activating PKA-CREB-BDNF signaling in the PFC of rats.

Research progress on the involvement of dopaminergic neurons in the ventral tegmental area in the regula-tion of anxiety-like behavior / 中国神经精神疾病杂志

Anxiety disorders,dopaminergic neurons and ventral tegmental area(VTA)are related closely.VTA dopaminergic neurons play an important role in the regulation of anxiety.Numerous research results in animals indicated that the VTA dopaminergic neurons,involving in multiple neural pathways,respectively regulate anxiety-like behavior in physiological or pathological condition.Dopamine,the main neurotransmitters in VTA regulates anxiety through dopamine D1 and D2 receptors.In addition,the VTA glutamate,GABA and acetylcholine also play directly or indirectly roles in regulating anxiety.The clinical imaging research showed that the integrity of dopaminergic VTA structural of anxiety disorder group is lower than healthy control.Current researches of VTA dopamine neurons involving in the regulation of anxiety-like behavior is developing at a high speed and deserving further exploration,which will further elucidate the pathogenesis and provide new ideas for prevention and treatment of anxiety disorders.

Research progress of non-ion channel genes related to juvenile myoclonic epilepsy / 中国神经精神疾病杂志

Juvenile myoclonic epilepsy(JME)is a common subtype of idiopathic generalized epilepsy(IGE).Genetic factors play an important role in JME.Multiple genes and chromosomal loci have been found to be associated with the onset of JME.According to the different mechanisms involved in gene mutations causing JME,JME related genes can be divided into ion channel genes and non-ion channel genes.The mechanism of action of ion channel genes has gradually been clarified which only accounts for a few cases.The mechanism of action of JME related non-ion channel genes is not yet clear.This article will review the research progress of JME related non-ion channel genes from three aspects:neurotransmitter related genes(CHRNA4,GRM4,SLC6A4),nervous system development related genes(TOP3B,CILK1,BRD2,EFHC1)and other related genes(TAP-1,CX36).

Research progress of neurotransmitter detection technology in live brains / 中国实验动物学报

As endogenous chemical substances,neurotransmitters play a vital role in maintaining normal life activities.Abnormal levels of neurotransmitters can lead to physical,mental,and some neurodegenerative diseases.However,the ultralow concentration,complex chemical properties,and release modes of neurotransmitters make their accurate detection in vivo a great challenge.To accurately monitor neurotransmitters in the brain and accurately understand the release kinetics of neurotransmitters,we reviewed several method commonly used in the past five years to detect neurotransmitters in vivo and their research progress.The basic principle and applicability of microdialysis,electrochemical sensors,and fluorescence sensors are introduced in detail.

Role of the synaptic plasticity in chronic pain comorbidity anxiety disorder / 中华行为医学与脑科学杂志

Chronic pain patients are often accompanied with anxiety disorder, which promote the development of each other's disease process to a certain extent and seriously affect the quality of life of patients.However, the mechanism regulating the comorbidity between the two has not been clarified.Synaptic remodeling is the alteration of synaptic structure and function, which affects the transmission of signals between neurons.Synaptic remodeling is a hot topic in the field of chronic pain and anxiety disorders, but only few studies have explored its pathological changes in chronic pain and anxiety disorders.By summarizing the relevant researches in recent years, the occurrence of chronic pain co-anxiety disorder is closely related to changes in synaptic structure, synaptic transmission efficiency and synaptic function in brain regions.Synaptic remodeling could lead to the decline of centra pain regulation ability and aggravate the progression of chronic pain accompanied by anxiety disorder through ionic amino acid receptors, neuronal transmission and interactions between neurons and glial cells.Understanding the latest research progress of the co-morbidity mechanism of chronic pain and anxiety disorder is helpful to provide theoretical basis and potential new targets for its treatment.

Correlation study between executive function and monoamine neurotransmitter of methamphetamine-dependent adolescents / 中华行为医学与脑科学杂志

Objective:To explore the characteristics of executive function and alterations in monoamine neurotransmitters in methamphetamine-dependent adolescents and to analyse the relationship between executive function and monoamine neurotransmitters.Methods:From January to March 2017, totally 50 female methamphetamine-dependent adolescents and 50 male methamphetamine-dependent adolescents were selected as the experimental group in two compulsory isolation drug rehabilitation centres in Sichuan Province, while normal adolescents (50 males and 50 females) matching the age and gender of the experimental group were recruited as the control group in a school.Executive function was tested by the N-back test, colour word interference test and Hanoita test, and serum levels of dopamine, 5-hydroxytryptamine, epinephrine and norepinephrine were measured using high-performance liquid chromatography with fluorescence detection.Statistical analysis was performed by SPSS 21.0 software.The t-test was used to compare the differences of executive function between the experimental group and control group, and Pearson correlation analysis was used to assess the correlation between executive functions and monoamine neurotransmitters in the experimental group. Results:The differences in the number of correct 0-back responses ((105.38±17.00) vs (114.05±5.29) ) and correct response time ((728.82±110.95) ms vs (652.24±89.88) ms), number of correct 2-back responses ((54.78±23.04) vs ( 74.01±12.01)) and correct response time ((585.74±245.35) ms vs (477.44±181.26) ms), the number of correct responses in the Stroop task ((29.68±7.19) vs (33.60±7.36)) and correct response time ((973.73±228.27) ms vs ( 916.11±98.54) ms), and the number of TOH movement steps ((99.42±32.83) vs (87.70±32.55)) were statistically significant in the experimental group compared to the control group(all P<0.05). In the experimental group, serum dopamine ((5.06±1.55) μg/mL vs (3.18±1.97) μg/mL), 5-hydroxytryptamine ((351.94±119.90) ng/mL vs (149.27±69.24) ng/mL), epinephrine ((555.66±225.55) ng/mL vs (129.20± 81.39) ng/mL), and norepinephrine ((3.63±0.96) ng/mL vs (2.03±0.64) ng/mL) were higher than those in the control group, all with statistically significant differences (all P<0.01). Correlation analysis of executive function with monoamine neurotransmitters showed that serum dopamine level in the experimental group was correlated significantly with the number of correct 0-back, 2-back responses, correct response time, and TOH movement steps ( r=-0.194, 0.170, -0.163, 0.198, 0.196, all P<0.05), 5-hydroxytryptamine level was negatively correlated with the number of correct 0-back, 2-back responses( r=-0.267, -0.375), and was positively correlated with correct response time ( r=0.243, 0.177). Adrenaline content was significantly correlated with the number of correct 0-back and 2-back responses, correct response time, and the number of correct Stroop test responses, correct response time ( r=-0.340, 0.212, -0.415, 0.170, -0.212, 0.178, all P<0.05). Norepinephrine level was correlated significantly with the number of correct 0-back responses, correct response times, correct 2-back responses, correct Stroop test responses, and TOH movement steps ( r=-0.245, 0.266, -0.291, -0.193, 0.226, all P<0.05). Conclusion:The executive function of methamphetamine-dependent adolescents is damaged to a certain extent and the content of monoamine neurotransmitter in serum is increased.There is a correlation between impairment in executive function and serum levels of monoamine neurotransmitters.