Evolution of neurotransmitter gamma-aminobutyric acid,glutamate and their receptors

Gamma-aminobutyric acid(GABA)and glutamate are two important amino acid neurotransmitters widely present in the nervous systems of mammals,insects,round worm,and platyhelminths,while their receptors are quite diversified across different animal phyla.However,the evolutionary mechanisms between the two conserved neurotransmitters and their diversified receptors remain elusive,and antagonistic interactions between GABA and glutamate signal transduction systems,in particular,have begun to attract significant attention.In this review,we summarize the extant results on the origin and evolution of GABA and glutamate,as well as their receptors,and analyze possible evolutionary processes and phylogenetic relationships of various GABAs and glutamate receptors.We further discuss the evolutionary history of Excitatory/Neutral Amino Acid Transporter(EAAT),a transport protein,which plays an important role in the GABA-glutamate“yin and yang”balanced regulation.Finally,based on current advances,we propose several potential directions of future research.

Evolution of neurotransmitter gamma-aminobutyric acid, glutamate and their receptors

Gamma-aminobutyric acid （GABA） and glutamate are two important amino acid neurotransmitters widely present in the nervous systems of mammals, insects, round worm, and platyhelminths, while their receptors are quite diversified across different animal phyla. However, the evolutionary mechanisms between the two conserved neurotransmitters and their diversified receptors remain elusive, and antagonistic interactions between GABA and glutamate signal transduction systems, in particular, have began to attract significant attention. In this review, we summarize the extant results on the origin and evolution of GABA and glutamate, as well as their receptors, and analyze possible evolutionary processes and phylogenetic relationships of various GABAs and glutamate receptors. We further discuss the evolutionary history of Excitatory/Neutral Amino Acid Transporter （EAAT）, a transport protein, which plays an important role in the GABA-glutamate ＂yin and yang＂ balanced regulation. Finally, based on current advances, we propose several potential directions of future research.

Targeting microglial neurotransmitter receptors as a therapeutic approach for Alzheimer’s disease

Alzheimer’s disease(AD)is a neurodegenerative condition that disrupts nerve cell function due to the misfolding and buildup of proteins,resulting in cognitive loss and aberrant behavior.Microglia cellsare one of the crucial immune cells in the central nervous system.Depending on their activation levels,microglia cells in the degenerative phase of AD can serve either neuroprotective or neurotoxic roles.Microglia cells express several neurotransmitter receptors that play distinct functions in the degenerative progression of AD.These receptors facilitate bidirectional communication between microglia and nerve cells.The neurotransmitter receptors on microglia cells can mediate or affect the neuroprotective or toxic effects of microglia cells,thereby affecting AD pathology.This paper focuses on the gamma-aminobutyric acid,glutaminergic,cannabinoid,cholinergic,and adrenergic receptors on microglia cells and their relationship with AD.Understanding how neurotransmitter receptors on microglia function in AD will be crucial for identifying potential treatment targets.

Plastic Changes of Synapses and Excitatory Neurotransmitter Receptors in Facial Nucleus Following Facial-facial Anastomosis

The remodeling process of synapses and neurotransmitter receptors of facial nucleus were observed. Models were set up by facial-facial anastomosis in rat. At post-surgery day （PSD） 0,7,21and 60, synaptophysin （p38）, NMDA receptor subunit 2A and AMPA receptor subunit 2 （GluR2） were observed by immunohistochemical method and semi-quantitative RT-PCR, respectively. Mean-while, the synaptic structure of the facial motorneurons was observed under a transmission electron microscope （TEM）. The intensity of p38 immunoreactivity was decreased, reaching the lowest value at PSD day 7, and then increased slightly at PSD 21. Ultrastructurally, the number of synapses in nucleus of the operational side decreased, which was consistent with the change in P38 immunoreactivity. NMDAR2A mRNA was down-regulated significantly in facial nucleus after the operation （P〈0.05）, whereas AMPAR2 mRNA levels remained unchanged （P〉0.05）. The synapses innervation and the expression of NMDAR2A and AMPAR2 mRNA in facial nucleus might be modified to suit for the new motor tasks following facial-facial anastomosis, and influenced facial nerve regeneration and recovery.

Effects of free radicals and amyloid β protein on the currents of expressed rat receptors in Xenopus oocytes

Objective To investigate the effects of free radicals (FRs) and amyloid β protein 1 40 (Aβ 1 40 ) on the functions of expressed neurotransmitter receptors (NRs) in Xenopus oocytes Methods Total RNA and messenger RNA (mRNA) was prepared from 3 month old Wistar rat brain tissues with Promega kits and microinjected into maturated Xenopus oocytes (stages Ⅴ Ⅵ) with 50?nl (50?ng) for each oocyte The microinjected oocytes were incubated with modified Bath's solution at 19 0℃±1 0℃ for receptor expression and their currents were recorded with double electrode voltage clamp technique Superoxide anion free radicals (SAFRs) were produced via a reaction system (HPX/XO) with hypoxanthine (HPX, 0 05?mol/L) and xanthine oxidase (XO, 0 1?U/L) In order to observe the effects of Aβ and SAFRs on the expressed glutamate receptor, HPX/XO and Aβ 1 40 were added to incubation solution at 12?h, 24?h and 96?h before recording Results The results showed that the oocytes expressed functional NRs originating from rat brain tissues These NRs included muscarinic acetylcholine (mACh), glutamate (Glu), dopamine (DA), serotonin (5 HT) and γ aminobutyric acid (GABA) The current characteristics of expressed receptors were inward currents carried by chloride ion with their equibrilium potentials close to -22?mV The extent of effect on the current of expressed glutamate receptor from rat brain was different among different Aβ concentrations and incubation times Aβ 1 40 at a concentration of 20?nmol/L had little effect on the currents of expressed rat brain glutamate receptors up to 24?h of incubation period; but the currents of glutamate receptor were significantly decreased (25% off, P <0 01) in the treatment of 60?nmol/L Aβ 1 40 over 24?h Moreover, when 20?nmol/L Aβ 1 40 was co incubated over 12?h with SAFRs produced by the reaction system of HPX/XO, it was found that the currents of expressed rat brain glutamate receptors had been changed markedly When the oocytes were co treated with 60?nmol/L Aβ 1 40 and SAFRs over a period of 12?h, the currents of glutamate receptor significantly decreased (21% off, P <0 05), and the decreased percentage reached 52% over 24?h co treatment with 60?nmol/L Aβ 1 40 and SAFRs In addition, vitamin E had a partial effect against this inhibitory effect Conclusion The results suggest that Aβ has a kind of inhibitory effect upon the current of the glutamate receptor, similar to the effects of free radicals The effects can be antagonized by vitamin E These imply that Aβ may play a role via inhibiting receptor function in the pathophysiology of Alzheimer's disease

Correlation analysis of Toll-like receptor 3 content in peripheral blood with electroencephalogram parameters and neurotransmitter content in children with intractable epilepsy

Objective:To detect the content of Toll-like receptor 3 (TLR3) in peripheral blood of children with intractable epilepsy, explore the correlation between TLR3 content and EEG parameters, neurotransmitter contents.Methods:37 cases of Intractable epilepsy children in our hospital during September 2016to June 2018 were chosen as Intractable epilepsy group, 30 cases of healthy volunteers who underwent physical examination in our hospital were treated as Normal control group. The levels of TLR3, neurotransmitter [5-hydroxytryptamine (5-HT), dopamine (DA), epinephrine (E), norepinephrine (NE)] and electroencephalogram parameters [alpha, beta, delta, theta] in peripheral blood of two groups were compared. Pearson test was used to evaluate the correlation of TLR3 content in peripheral blood with EEG parameters and neurotransmitter content in children with intractable epilepsy.Results: Content of TLR3 in peripheral blood of Intractable epilepsy group was significantly higher than that of Normal control group;the alpha power and theta power of EEG parameters were lower than those of Normal control group;contents of neurotransmitters such as 5-HT, DA, E and NE were significantly lower than those of Normal control group (P<0.05). The correlation analysis showed that content of TLR3 in peripheral blood of children with intractable epilepsy was negatively correlated with levels of alpha and theta power of EEG, positively correlated with content of neurotransmitters such as 5-HT, DA, E and NE (P<0.05), but had no significant correlation was found with level of beta and delta power (P>0.05).Conclusion: The abnormal increase of TLR3 in peripheral blood of children with intractable epilepsy may be one of the direct causes of neurological impairment in children with intractable epilepsy.

Wake-promoting effects of vagus nerve stimulation after traumatic brain injury: upregulation of orexin-A and orexin receptor type 1 expression in the prefrontal cortex

Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expres- sion coincides with the projection area of the vagus nerve in the brain. Vagus nerve stimulation has been shown to decrease the amounts of daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury. In the present study, we investigated whether vagus nerve stimulation promotes wakefulness and affects orexin expression. A rat model of traumatic brain injury was established using the free fall drop method. In the stimulated group, rats with traumatic brain injury received vagus nerve stimulation （frequency, 30 Hz, current, 1.0 mA; pulse width, 0.5 ms; total stimulation time, 15 minutes）. In the antagonist group, rats with traumatic brain injury were intracerebroventricularly injected with the orexin receptor type 1 （OXIR） antagonist SB334867 and received vagus nerve stimulation. Changes in consciousness were observed after stimulation in each group. Enzyme-linked immunosorbent assay, western blot assay and immunohistochemistry were used to assess the levels of orexin-A and OX1R expression in the prefrontal cortex. In the stimulated group, consciousness was substantially improved, orexin-A protein expression gradually increased within 24 hours after injury and OX1R expres- sion reached a peak at 12 hours, compared with rats subjected to traumatic brain injury only. In the antagonist group, the wake-promoting effect of vagus nerve stimulation was diminished, and orexin-A and OX1R expression were decreased, compared with that of the stim- ulated group. Taken together, our findings suggest that vagus nerve stimulation promotes the recovery of consciousness in comatose rats after traumatic brain injury. The upregulation of orexin-A and OXIR expression in the prefrontal cortex might be involved in the wake-promoting effects of vagus nerve stimulation.

Ion Transport Signal Pathways Mediated by Neurotransmitter(Biogenic Amines) of Litopenaeus vannamei Under Low Salinity Challenge

The Pacific white shrimp, Litopenaeus vannamei, is widely farmed in China. Salinity is a major environmental factor that affects its growth and distribution. Crustacean hyperglycemic hormone is verified to participate in ion transport in response to the salinity challenge mediated by endocrine neurotransmitters(biogenic amines, BAs). In the present study, the contents of BAs and expressions of their receptors were detected in gills of Litopenaeus vannamei exposed to low salinity. The intracellular signaling molecules such as cyclic adenosine monophosphate(cAMP), protein kinase A(PKA), 14-3-3 protein, FXYD2 protein and cAMP response element-binding protein(CREB) were detected. The effects of low salinity on the expressions of Na^+-K^+-ATPase, Na^+/K^+/2 Cl-co-transporter and Cl-transporter and activity of Na^+-K^+-ATPase were also analyzed. The results showed that dopamine and epinephrine concentrations and their receptor expressions were significantly affected by low salinity. The changes of c AMP and PKA were obvious and the expressions of 14-3-3 and FXYD2 peaked at early stages. However, the expression of CREB was only significantly up-regulated on day 9. The activity and expression of Na^+-K^+-ATPase(α subunit) reached a peak on day 1. The expressions of Na^+/K^+/2 Cl-co-transporter and Cl-transporter up-regulated obviously. It suggests that BAs can activate the cAMP-PKA pathway, which further acts on the 14-3-3 and FXYD2 proteins, and ultimately improve the activity of Na^+-K^+-ATPase. Furthermore, after BAs stimulate the cAMP-PKA pathway, PKA phosphorylates the transcription factor CREB and regulates the expressions of ion transport enzymes/transporters. The results in this study are helpful for understanding the response mechanism of endocrine neurotransmitters on osmoregulation in crustaceans.

The dopaminergic system and Alzheimer's disease

Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.

Effects of Kaixin Jieyu Decoction(开心解郁汤)on Behavior, Monoamine Neurotransmitter Levels, and Serotonin Receptor Subtype Expression in the Brain of A Rat Depression Model

Objective： To determine the mechanisms underlying the anti-depressant effects of Kaixin JieyuDecoction （开心解郁汤, KJD） by investigating the effects of KJD on behavior, monoamine neurotransmitterlevels, and serotonin （5-HT） receptor subtype expression in the brain in a rat model of depression. Methods：The rat depression model was established using chronic unpredictable mild stress （CUMS）. Forty-eight SpragueDawley rats were randomly divided into control, depression model （CUMS）, CUMS＋KJD （7.7 g/kgl-d1 ofcrude drug）, and CUMS＋fluoxetine （2.4 mg/kgl.d1） groups （n=12 in each group）, and the treatments lastedfor 21 days. We regularly evaluated body weight, sucrose consumption, and horizontal and vertical activityscores in open-field tests. The content of the monoamine neurotransmitters 5-HT, norepinephrine （NE）, anddopamine （DA） and the DA metabolite homovanillic acid in the cerebral cortex, and 5-HT1A and 5-HT2A receptormRNA in the cerebral cortex and the hippocampus, were determined respectively by high-performance liquidchromatography-coularray electrochemical detector and real-time polymerase chain reaction. Results： Comparedwith the control group, CUMS rats showed a variety of depression-like behavioral changes, including a significantreduction in body weight, sucrose consumption, and horizontal and vertical activity scores in open-field tests（P〈0.05 or ,P〈0.01）, and a significant decrease in 5-HT and NE levels and 5-HT2A receptor mRNA expression.In contrast, they showed a significant increase in 5-HT1A receptor mRNA expression in the cerebral cortex. Inthe hippocampus, 5-HT1A receptor mRNA expression was lower whereas 5-HT2A receptor mRNA expressionwas higher than in the control group （P〈0.05 or P〈0.01）. Treatment with KJD or fluoxetine partially attenuatedthese changes （,P〈0.05 or ,P〈0.01）. Conclusion： KJD could normalize the levels of 5-HT and NE and adjust thebalance of 5-HT2A and 5-HT2A receptor expression in rat cerebrum, and this may be one of mechanisms ofantidepressant effects of KJD.

Antidepressant effect of bioactive compounds from Paecilomyces tenuipes in mice and rats

A bioactive compound from Paecilomyces tenuipes（BCPT）has an inhibitory effect on monoamine oxidase A（MAO-A）in vitro.Researchers have thought that BCPT may be a potential antidepressant.The MAO-A suppressor moclobemide served as a control,and this study investigated the mechanisms of BCPT as an antidepressant.Results demonstrated that BCPT induced significantly increased sucrose intake in chronic unpredictable stressed rats,shortened immobility time in forced swimming mice,improved the scores of blepharoptosis and akinesia in reserpine-treated mice,increased the number of 5-hydroxy tryptophan-induced head-twitches,remarkably enhanced the expression of hippocampus mineralcorticoid receptor and glucocorticoid receptor mRNA,decreased the ratio of mineralcorticoid receptor to glucocorticoid receptor and raised the levels of dopamine,norepinephrine and 5-hydroxytryptamine,while decreasing hydroxyindole acetic acid levels or dihydroxy-phenyl acetic acid in chronic unpredictable stressed rats.Behavioral test results suggested that BCPT potentially had antidepressant-like activity.Meanwhile,BCPT increased the levels of neurotransmitters,and mineralcorticoid receptor and glucocorticoid receptor mRNA in the hippocampus,which may be an important mechanism of its antidepressant effect.

恶心呕吐的分子机制及神经回路研究进展

恶心和呕吐是常见的临床症状,通常与多种疾病和治疗过程相关。这些症状的主观性使其难以准确描述,且其发生机制复杂,涉及多种组织器官、受体和神经回路。恶心和呕吐的药物治疗效果有限,且常伴有不良反应。恶心呕吐对多种手术病人的早期康复产生了显著影响,因此了解其发生机制并改善预防和治疗措施是当前研究的重要方向。近年来的相关研究集中在恶心和呕吐的分子及神经回路机制上,取得了重要进展。此外,围手术期尤其是术后恶心呕吐(postoperative nausea and vomiting, PONV)的临床因素和研究现状也得到了关注,以期改善病人的治疗体验和康复效果。本文综述恶心呕吐病理发生相关受体和神经回路机制以及PONV的研究进展,为临床预防及治疗PONV提供理论参考。

针灸治疗偏头痛作用机制研究进展

针灸治疗偏头痛的机制主要包括调节脑部血流速度、影响神经递质释放、抑制炎性反应、调节中枢镇痛机制、抑制神经元激活、抑制胶质细胞活化、促进阿片类受体、调节脑-肠-菌轴等。目前,针灸治疗偏头痛临床研究逐渐丰富,但仍存在以下问题:治法相对单一,主要集中在针刺研究方向;没有区别证型,未发挥最大疗效;缺乏对机制之间联系及整体的研究等。今后,可加强对灸法治疗偏头痛机制的研究,促进临床治疗多样性,充分发挥针灸治疗偏头痛的作用;研究针灸治疗不同证型偏头痛机制的区别,充分考虑患者个体差异性,提高临床疗效;进一步挖掘不同机制之间的内在联系,促进针灸治疗偏头痛整体机制研究的发展。

Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury

Human umbilical cord mesenchymal stem cells(hUC-MSCs)are a promising candidate for spinal cord injury(SCI)repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources.However,modest clinical efficacy hampered the progression of these cells to clinical translation.This discrepancy may be due to many variables,such as cell source,timing of implantation,route of administration,and relevant efficacious cell dose,which are critical factors that affect the efficacy of treatment of patients with SCI.Previously,we have evaluated the safety and efficacy of 4×10^(6) hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models.To search for a more accurate dose range for clinical translation,we compared the effects of three different doses of hUC-MSCs-low(0.25×10^(6) cells/kg),medium(1×10^(6) cells/kg)and high(4×10^(6) cells/kg)-on subacute SCI repair through an elaborate combination of behavioral analyses,anatomical analyses,magnetic resonance imaging-diffusion tensor imaging(MRI-DTI),biotinylated dextran amine(BDA)tracing,electrophysiology,and quantification of mRNA levels of ion channels and neurotransmitter receptors.Our study demonstrated that the medium dose,but not the low dose,is as efficient as the high dose in producing the desired therapeutic outcomes.Furthermore,partial restoration of theγ-aminobutyric acid type A(GABAA)receptor expression by the effective doses indicates that GABAA receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord.Overall,this study revealed that intrathecal implantation of 1×10^(6) hUC-MSCs/kg is an alternative approach for treating subacute SCI.

踝三针对腰椎间盘突出根性痛大鼠中枢镇痛递质的影响

目的:探讨踝三针对腰椎间盘突出根性痛镇痛作用的机制。方法:雄性SD大鼠60只随机分为正常对照组、假手术对照组、模型对照组、来比林对照组、常规体针组、踝三针治疗组,分别采用肌肉注射药物来比林、常规穴针刺、踝三针穴位针刺治疗。测各组机械痛阈值和5-羟色胺(5-HT)含量。结果:大鼠痛阈值踝三针治疗组与模型对照组同时点比较显著增高(P<0.05);30 min时点痛阈值来比林对照组、常规体针组显著高于模型对照组,踝三针治疗组与来比林对照组、常规体针组比显著增加(均P<0.05)。5-HT测量值踝三针治疗组与模型对照组、来比林对照组在相同时点比较差异具有非常显著性意义(P<0.01);30 min时点5-HT测量值踝三针治疗组显著高于常规体针组(P<0.05)。结论:踝三针镇痛作用与脑内5-HT递质含量增加密切相关。

The effects of pinellia total alkaloids on the amino acid concentration and the GABAA receptor expression in hippocampus region of epileptic rats

The antiepileptic effect of pinellia total alkaloids（PTA） on penicillin（PNC） chronically kindled rats was investigated. We investigated the effects of PTA on Glu,Asp,Gly andγ-aminobutyric acid（GABA） concentrations and the expression level of cerebral GABA_A receptor in hippocampus.The influence of PTA on epilepsy seizure latency and degree in PNC chronically kindled rats were observed.High performance liquid chromatography（HPLC） was adopted to measure the concentrations of Glu, Asp,Gly and GABA in hippocampus. Reverse transcriptase-polymerase chain reaction （RT-PCR） was used to determine the expression of cerebral GABAA receptor mRNA. Compared with normal rats, the levels of GABA and Gly decreased obviously while the level of Glu and Asp increased significantly in model rats. The cerebral GABAA receptor mRNA level was also decreased at the same time. The difference was statistically different compared to the control group. PTA could prolong the latent period of the penicillin induced seizure and weaken the extent of seizure, compared with the model group without PTA treatment. Moreover, PTA increased the level of GABA and the expression level of GABAA receptor, while decreased the level of Glu significantly. However, it had no obvious effect on the level of Gly and Asp. Pre-treatment of PTA can also increase the GABAA receptor mRNA level. In conclusion, PTA could alleviate the PNC chronically kindled rat seizure. It increased the GABA level and the expression of GABAA receptor, and it decreased the Glu concentration.

睡眠-觉醒的神经调节机制

睡眠-觉醒是一个涉及多系统、多中枢的生理过程,具有复杂的神经调节机制。促进觉醒的系统大部分起源于一系列明确的细胞群,并且这些细胞群与各自明确的神经递质相关联。促进睡眠的系统主要与大脑中抑制性神经递质γ氨基丁酸(GABA)有关,脑中不同部位的GABA神经元共同起到了促进睡眠的作用。为了更好地理解睡眠-觉醒的神经调节机制以及为新药的开发提供线索,本文对促进觉醒的系统和促进睡眠的系统的功能及其有关的神经递质进行了系统描述。

肉蔻五味丸抗抑郁作用及机制研究

目的:探讨肉蔻五味丸的抗抑郁作用及其作用机制,为临床用药提供依据。方法:雄性C57BL/6小鼠随机分为空白对照组(control)、模型组(model)、盐酸氟西汀(fluoxetine 10 mg/kg)阳性药组、肉蔻五味丸低剂量(rk 0.2 g/kg)组、肉蔻五味丸高剂量(rk0.5 g/kg)组,给予慢性轻度不可预见性加孤养刺激建立抑郁模型,建模同时灌胃给予小鼠药物治疗。给药五周后,进行行为学检测(强迫游泳实验、悬尾实验和高架十字迷宫实验);LC-MS/MS法检测海马内5-羟色胺(5-HT)等神经递质含量;q PCR法检测海马内5-羟色胺1A受体(5-HT1AR)、5-羟色胺7受体(5-HT7R)、GABAA型受体(GABAAR)、GABAB型受体(GABABR)、神经生长因子(NGF)和胶质细胞源神经营养因子(GDNF)基因表达;ELISA法检测小鼠血清内促肾上腺皮质激素(ACTH)和皮质酮(COR)的含量。结果:低剂量肉蔻五味丸有效减少慢性应激导致的小鼠游泳和悬尾不动时间的增加(P<0.05),降低模型组小鼠进入高架中央区活动时间(P<0.05),逆转小鼠海马5-HT(P<0.001)、5-HT/5-HIAA(P<0.001)的降低以及GABABR(P<0.01)、NGF(P<0.01)、GDNF(P<0.001)基因表达的降低(P<0.05),并且降低血清中ACTH的水平(P<0.05)。结论:肉蔻五味丸低剂量具有抗抑郁作用,其机制可能与提高抑郁小鼠海马5-HT含量、GABABR、NGF和GDNF基因表达以及降低血清中ACTH的水平有关。

突触前代谢型谷氨酸受体调节神经递质的释放

谷氨酸通过激活离子型受体(iGluR)介导快速兴奋性突触传递,参与脑内几乎所有生理过程。谷氨酸过量释放可导致与脑缺血、缺氧及变性疾病有关的兴奋毒作用,最终引起神经元的死亡。代谢型谷氨酸受体(mGluRs)是一个与G-蛋白偶联的受体家族,分三型共八个亚型。其中Ⅱ和Ⅲ型mGluRs主要位于突触前,发挥对谷氨酸释放的负反馈调节。Ⅲ型mGluRs中的mGluR,位于谷氨酸能末梢突触前膜的活性区,发挥自身受体的作用,对正常情况下突触传递过程的谷氨酸释放进行负反馈调节;而属于Ⅱ型的mGluR2及属于Ⅲ型的mGluR4和mGluR8,则位于远离突触前膜活性区的外突触区,因而正常突触传递过程中释放的谷氨酸量不能激活它们。只有在突触传递增强的情况下才被激活,抑制递质的释放。另外,mGluRs还分布在GABA能纤维末梢,通过突触前机制抑制GABA的释放。对突触前膜受体尤其是位于外突触区的mGluRs受体的研究,将有可能开发出理想的工具药,从而预防和阻止谷氨酸过量释放引起的神经毒及神经元的死亡。

从受体角度研究睡眠-觉醒调控机制

生物日节律是地球生物受昼夜更替影响的普遍现象,是生命活动的基本组成,几乎涉及机体所有组织与器官的生理活动。这种全身协调的动态变化是多种机制的共同参与和信息整合。在所有参与睡眠觉醒动态循环调控的环节中,受体至关重要,为细胞内信号效应的启动点,同时亦是重要的干预靶点。对目前已知参与睡眠-觉醒循环调节受体的种类进行归纳,并对其功能研究进展进行阐述,有助于进一步了解睡眠-觉醒的生理过程,亦为干预其病理生理变化的研究提供有效信息。