胃肠道的大部分区域都存在着一种特殊的间质细胞——Cajal间质细胞(interstitial cells of Cajal,ICCs)。尽管在100多年前它们的存在就已被发现,但是直到最近几十年的研究才逐渐揭示了它们的功能。在胃肠道,ICCs被认为是平滑肌自发性节...胃肠道的大部分区域都存在着一种特殊的间质细胞——Cajal间质细胞(interstitial cells of Cajal,ICCs)。尽管在100多年前它们的存在就已被发现,但是直到最近几十年的研究才逐渐揭示了它们的功能。在胃肠道,ICCs被认为是平滑肌自发性节律性电活动,即"基本电节律"(又称"慢波")的起搏细胞,并介导神经至平滑肌的神经信号传递活动。除胃肠道外,ICC样细胞同样存在于其它内脏平滑肌,如泌尿、生殖系统以及血管平滑肌等。本文仅就这些内脏平滑肌ICCs的功能做一简单综述。展开更多
目的探讨法尼醇X受体(farnesoid X receptor,FXR)作为一种核激素受体对情感、社交或记忆等神经行为的调节作用。方法通过一系列行为学测试,包括高架十字迷宫,强迫游泳、社交活动和避暗,以及LC-MS/MS法检测大脑不同区域的神经递质,评估FX...目的探讨法尼醇X受体(farnesoid X receptor,FXR)作为一种核激素受体对情感、社交或记忆等神经行为的调节作用。方法通过一系列行为学测试,包括高架十字迷宫,强迫游泳、社交活动和避暗,以及LC-MS/MS法检测大脑不同区域的神经递质,评估FXR基因敲除(knockout,KO)对♀小鼠中枢神经系统功能的影响。结果 FXR KO导致小鼠在强迫游泳中不动时间延长(P<0.01),进入高架十字迷宫开放臂次数增加(P<0.01),逗留时间延长,同时社交活动增强(P<0.01),但对避暗行为中的潜伏期和错误次数无明显影响。FXR KO亦导致小鼠海马γ-氨基丁酸(GABA,P<0.05)、谷氨酸(Glu,P<0.05)、去甲肾上腺素(NE,P<0.01)以及GABA/Glu(P<0.05)明显降低,但对前额叶相关神经递质无明显影响。结论 FXR可能参与调控中枢神经系统中神经递质稳态平衡,进而影响动物的情感和社交行为。展开更多
Therapeutic progress in neurodegenerative conditions such as Parkinson’s disease has been hampered by a lack of detailed knowledge of its molecular etiology.The advancements in genetics and genomics have provided fun...Therapeutic progress in neurodegenerative conditions such as Parkinson’s disease has been hampered by a lack of detailed knowledge of its molecular etiology.The advancements in genetics and genomics have provided fundamental insights into specific protein players and the cellular processes involved in the onset of disease.In this respect,the autophagy-lysosome system has emerged in recent years as a strong point of convergence for genetics,genomics,and pathologic indications,spanning both familial and idiopathic Parkinson’s disease.Most,if not all,genes linked to familial disease are involved,in a regulatory capacity,in lysosome function(e.g.,LRRK2,alpha-synuclein,VPS35,Parkin,and PINK1).Moreover,the majority of genomic loci associated with increased risk of idiopathic Parkinson’s cluster in lysosome biology and regulation(GBA as the prime example).Lastly,neuropathologic evidence showed alterations in lysosome markers in autoptic material that,coupled to the alpha-synuclein proteinopathy that defines the disease,strongly indicate an alteration in functionality.In this Brief Review article,I present a personal perspective on the molecular and cellular involvement of lysosome biology in Parkinson’s pathogenesis,aiming at a larger vision on the events underlying the onset of the disease.The attempts at targeting autophagy for therapeutic purposes in Parkinson’s have been mostly aimed at“indiscriminately”enhancing its activity to promote the degradation and elimination of aggregate protein accumulations,such as alpha-synuclein Lewy bodies.However,this approach is based on the assumption that protein pathology is the root cause of disease,while pre-pathology and pre-degeneration dysfunctions have been largely observed in clinical and pre-clinical settings.In addition,it has been reported that unspecific boosting of autophagy can be detrimental.Thus,it is important to understand the mechanisms of specific autophagy forms and,even more,the adjustment of specific lysosome functionalities.Indeed,lysosomes ex展开更多
N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine quinone(6PPDQ)has attracted significant attention due to its highly acute lethality to sensitive salmonids.However,studies investigating the mechanisms underlying it...N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine quinone(6PPDQ)has attracted significant attention due to its highly acute lethality to sensitive salmonids.However,studies investigating the mechanisms underlying its acute toxicity have been lacking.In this work,we demonstrated the sensitivity of rainbow trout to 6PPDQ-induced mortality.Moribund trout exhibited significantly higher brain concentrations of 6PPDQ compared to surviving trout.In an in vitro model using human brain microvascular endothelial cells,6PPDQ can penetrate the blood–brain barrier and enhance blood–brain barrier permeability without compromising cell viability.The time spent in the top of the tank increased with rising6PPDQ concentrations,as indicated by locomotion behavior tests.Furthermore,6PPDQ influenced neurotransmitter levels and m RNA expression of neurotransmission-related genes in the brain and exhibited strong binding affinity to target neurotransmission-related proteins using computational simulations.The integrated biomarker response value associated with neurotoxicity showed a positive linear correlation with trout mortality.These findings significantly contribute to filling the knowledge gap between neurological impairments and apical outcomes,including behavioral effects and mortality,induced by6PPDQ.展开更多
Cortical spreading depression is a technique used to depolarize neurons. During focal or global ischemia, cortical spreading depression-induced preconditioning can enhance tolerance of further injury. However, the und...Cortical spreading depression is a technique used to depolarize neurons. During focal or global ischemia, cortical spreading depression-induced preconditioning can enhance tolerance of further injury. However, the underlying mechanism for this phenomenon remains relatively unclear. To date, numerous issues exist regarding the experimental model used to precondition the brain with cortical spreading depression, such as the administration route, concentration of potassium chloride, induction time, duration of the protection provided by the treatment, the regional distribution of the protective effect, and the types of neurons responsible for the greater tolerance. In this review, we focus on the mechanisms underlying cor- tical spreading depression-induced tolerance in the brain, considering excitatory neurotransmission and metabolism, nitric oxide, genomic reprogramming, inflammation, neurotropic factors, and cellular stress response. Specifically, we clarify the procedures and detailed information regarding cortical spreading depression-induced preconditioning and build a foundation for more comprehensive investigations in the field of neural regeneration and clinical application in the future.展开更多
The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions a...The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.展开更多
目的:探索前列腺Cajal间质细胞(interstitial cells of Cajal,ICCs)与交感神经及平滑肌细胞之间的形态及功能学联系。方法:(1)制作豚鼠前列腺组织冰冻切片并进行双重免疫荧光染色。使用酪氨酸激酶受体(c-Kit)作为ICCs的标记物,酪氨酸羟...目的:探索前列腺Cajal间质细胞(interstitial cells of Cajal,ICCs)与交感神经及平滑肌细胞之间的形态及功能学联系。方法:(1)制作豚鼠前列腺组织冰冻切片并进行双重免疫荧光染色。使用酪氨酸激酶受体(c-Kit)作为ICCs的标记物,酪氨酸羟化酶(tyrosine hydroxylase,TH)和多巴胺β羟化酶(dopamineβ-hydroxylase,DβH)作为交感神经纤维的标记物,α肌动蛋白(α-actin)作为平滑肌细胞的标记物。另外,分别对α1-肾上腺素受体与c-Kit以及缝隙连接蛋白Connexin43(Cx43)与c-Kit进行免疫荧光双重标记。(2)将前列腺肌条固定于灌流槽中,记录去甲肾上腺素(norepinephrine,NE)诱发的肌条收缩幅度和频率,以及加入Glivec后肌条收缩幅度和频率的变化。结果:(1)免疫荧光组织化学标记结果显示:ICCs与交感神经纤维、平滑肌细胞平行分布,ICCs边缘与交感神经、平滑肌细胞边缘密切接触,c-Kit标记的ICCs上存在α1-肾上腺素受体和缝隙连接蛋白Cx43的共表达。(2)在去甲肾上腺素的刺激下前列腺平滑肌肌条收缩幅度为(0.98±0.16)g,收缩频率为(2.54±0.28)次/min。使用Glivec后肌条收缩幅度显著下降,50μmol/L组为(0.56±0.07)g(P<0.01),200μmol/L组为(0.25±0.05)g(P<0.01),收缩频率未见明显改变,50μmol/L组为(2.67±0.32)次/min(P>0.05),200μmol/L组为(2.75±0.31)次/min(P>0.05)。结论:豚鼠前列腺ICCs具有介导前列腺交感神经信号,支配平滑肌活动的形态和功能学基础。展开更多
Hepatic encephalopathy is a serious neuropsychiatric complication caused by liver failure,which is characterized by the development of cognitive and motor disorders into coma.Typically,hepatic encephalopathy can be di...Hepatic encephalopathy is a serious neuropsychiatric complication caused by liver failure,which is characterized by the development of cognitive and motor disorders into coma.Typically,hepatic encephalopathy can be divided into three types(A,B,and C)according to the etiology.Type A hepatic encephalopathy(AHE)caused by acute liver failure seriously affects the prognosis of patients,ranging from mild neuropsychological changes to coma,brain edema,and even death.So far,the research on the pathogenesis of AHE has focused on the toxic effects of ammonia on the central nervous system,metabolic disorders(glutamine and lactate accumulation),neurotransmission alteration,systemic inflammation,especially neuro-inflammation.All these mechanisms are not independent,but mutually have synergistic effects.In clinic,treatment of AHE based on only one mechanism is often ineffective.To clarify the pathogenesis and the interaction among the mechanisms will be beneficial to the effective treatment of AHE and reduce the mortality.The aim of this review is to provide comprehensive scientific evidence for the clinical treatment of AHE via collecting and analyzing the latest mechanism of AHE,and clarifying the relationship among these mechanisms combing the investigation of the latest research progress of drug treatment of acute liver failure.Consequently,we find that the pathogenesis of AHE is a complex neurocognitive disorder shaped by interactions among hyperammonemia,inflammation,and changes in neurotransmission,the signaling pathways thereby integrating the inflammatory and neurological inputs to impact pathophysiological or neurobehavioral outcomes.展开更多
目的观察黄芩素对阿尔茨海默病(AD)大鼠发病早期认知功能和皮层、海马组织蛋白表达谱的影响,探讨其作用机制。方法实验大鼠随机分为对照组、模型组、黄芩素组,每组12只。黄芩素组大鼠予黄芩素药液灌胃,模型组和对照组大鼠予等量生理盐...目的观察黄芩素对阿尔茨海默病(AD)大鼠发病早期认知功能和皮层、海马组织蛋白表达谱的影响,探讨其作用机制。方法实验大鼠随机分为对照组、模型组、黄芩素组,每组12只。黄芩素组大鼠予黄芩素药液灌胃,模型组和对照组大鼠予等量生理盐水灌胃。灌胃体积均为2 m L,连续10 d。利用Morris水迷宫评估治疗效果,并运用双向凝胶电泳技术对脑组织蛋白进行分离,考马斯蓝染显色,应用PDQuest8.0软件对双向电泳图谱进行差异分析,通过MALDI-TOF-MS/MS和数据库查询鉴定差异明显的蛋白质点,并利用String在线分析软件对差异表达蛋白进行生物信息学分析。结果黄芩素可显著缓解β-淀粉样蛋白(Aβ)1-40导致的认知功能减退。黄芩素作用下,位于大鼠大脑皮层和海马组织的8种蛋白表达水平变化明显。质谱鉴定结果显示,差异蛋白涉及4种生物学功能,与神经传导关系最为密切,其中3种蛋白与其他蛋白存在相互作用关系。结论黄芩素对AD大鼠早期认知功能损伤的改善作用与其能够调节神经传导相关蛋白的表达相关。展开更多
AIM To investigate whether the adipocytes derived hormone adiponectin(ADPN) affects the mechanical responses in strips from the mouse gastric fundus. METHODS For functional experiments, gastric strips from the fundal ...AIM To investigate whether the adipocytes derived hormone adiponectin(ADPN) affects the mechanical responses in strips from the mouse gastric fundus. METHODS For functional experiments, gastric strips from the fundal region were cut in the direction of the longitudinal muscle layer and placed in organ baths containing KrebsHenseleit solution. Mechanical responses were recorded via force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrical field stimulation(EFS) was applied via two platinum wire rings through which the preparation was threaded. The effects of ADPN were investigated on the neurally-induced contractile and relaxant responses elicited by EFS. The expression of ADPN receptors, Adipo-R1 and Adipo-R2, was also evaluated by touchdown-PCR analysis. RESULTS In the functional experiments, EFS(4-16 Hz) elicited tetrodotoxin(TTX)-sensitive contractile responses. Addition of ADPN to the bath medium caused a reduction in amplitude of the neurally-induced contractile responses(P < 0.05). The effects of ADPN were no longer observed in the presence of the nitric oxide(NO) synthesis inhibitor L-NG-nitro arginine(L-NNA)(P > 0.05). The direct smooth muscle response to methacholine was not influenced by ADPN(P > 0.05). In carbachol precontracted strips and in the presence of guanethidine, EFS induced relaxant responses. Addition of ADPN to the bath medium, other than causing a slight and progressive decay of the basal tension, increased the amplitude of the neurally-induced relaxant responses(P < 0.05). Touchdown-PCR analysis revealed the expression of both Adipo-R1 and Adipo-R2 in the gastric fundus.CONCLUSION The results indicate for the first time that ADPN is able to influence the mechanical responses in strips from the mouse gastric fundus.展开更多
Establishment of animal models of schizophrenia is critical for both understanding the mechanisms underlying this severe mental disease and developing new antipsychotics. This paper starts from the theoretical root of...Establishment of animal models of schizophrenia is critical for both understanding the mechanisms underlying this severe mental disease and developing new antipsychotics. This paper starts from the theoretical root of sensory gating, the 損rotection-of-processing?theory, then thoroughly describes the representative studies over the past decade on the mechanism underlying prepulse inhibition and on those underlying modulation of prepulse inhibition, which is the normal startle suppression caused by the weak stimulus preceding the intense startling stimulus. The main methods for inducing prepulse inhibition deficits in experimental animals include: ⅰ) modulations of neuro- transmission that are closely associated with schizophrenia; ⅱ) focal lesions or pharmacological manipulations of brain structures in the cortico-striato-pallido-pontine circuit; and ⅲ) maternal deprivation or social isolation. Six essential topics for studies in modeling schizophrenia are suggested at the last part of this review.展开更多
In recent years,many studies have investigated the correlations between Parkinson's disease(PD)and vitamin D status,but the conclusion remains elusive.The present review focuses on the associations between PD and ...In recent years,many studies have investigated the correlations between Parkinson's disease(PD)and vitamin D status,but the conclusion remains elusive.The present review focuses on the associations between PD and serum vitamin D levels by reviewing studies on the associations of PD with serum vitamin D levels and vitamin D receptor(VDR)gene polymorphisms from PubMed,Web of Science,Cochrane Library,and Embase databases.We found that PD patients have lower vitamin D levels than healthy controls and that the vitamin D concentrations are negatively correlated with PD risk and severity.Furthermore,higher vitamin D concentrations are linked to better cognitive function and mood in PD patients.Findings on the relationship between VDR gene polymorphisms and the risk of PD are inconsistent,but the Fokl(C/M)polymorphism is significantly linked with PD.The occurrence of Fokl(CT)gene polymorphism may influence the risk,severity,and cognitive ability of PD patients,while also possibly influencing the effect of Vitamin D3 supplementation in PD patients.In view of the neuroprotective effects of vitamin D and the close association between vitamin D and dopaminergic neurotransmission,interventional prospective studies on vitamin D supplementation in PD patients should be conducted in the future.展开更多
Background Neuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject t...Background Neuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters, which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters （inhibitory GABA transporters GAT and excitatory glutamate transporters GT）. Neuronal hyper-excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission. SNAP-25, which is one of the SNARE complexes, can modulate the release of neurotransmitters. Glia glutamate transporter （GLT） is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS. The role of SNAP-25 and GLT as well as GAT is not clearly understood.展开更多
基金supported by the National Natural Science Foundation of China(No.10672103)
文摘胃肠道的大部分区域都存在着一种特殊的间质细胞——Cajal间质细胞(interstitial cells of Cajal,ICCs)。尽管在100多年前它们的存在就已被发现,但是直到最近几十年的研究才逐渐揭示了它们的功能。在胃肠道,ICCs被认为是平滑肌自发性节律性电活动,即"基本电节律"(又称"慢波")的起搏细胞,并介导神经至平滑肌的神经信号传递活动。除胃肠道外,ICC样细胞同样存在于其它内脏平滑肌,如泌尿、生殖系统以及血管平滑肌等。本文仅就这些内脏平滑肌ICCs的功能做一简单综述。
基金supported by grants from Parkinson Canada,The Weston Brain Foundation and the Euregio Science Fund(to MV).
文摘Therapeutic progress in neurodegenerative conditions such as Parkinson’s disease has been hampered by a lack of detailed knowledge of its molecular etiology.The advancements in genetics and genomics have provided fundamental insights into specific protein players and the cellular processes involved in the onset of disease.In this respect,the autophagy-lysosome system has emerged in recent years as a strong point of convergence for genetics,genomics,and pathologic indications,spanning both familial and idiopathic Parkinson’s disease.Most,if not all,genes linked to familial disease are involved,in a regulatory capacity,in lysosome function(e.g.,LRRK2,alpha-synuclein,VPS35,Parkin,and PINK1).Moreover,the majority of genomic loci associated with increased risk of idiopathic Parkinson’s cluster in lysosome biology and regulation(GBA as the prime example).Lastly,neuropathologic evidence showed alterations in lysosome markers in autoptic material that,coupled to the alpha-synuclein proteinopathy that defines the disease,strongly indicate an alteration in functionality.In this Brief Review article,I present a personal perspective on the molecular and cellular involvement of lysosome biology in Parkinson’s pathogenesis,aiming at a larger vision on the events underlying the onset of the disease.The attempts at targeting autophagy for therapeutic purposes in Parkinson’s have been mostly aimed at“indiscriminately”enhancing its activity to promote the degradation and elimination of aggregate protein accumulations,such as alpha-synuclein Lewy bodies.However,this approach is based on the assumption that protein pathology is the root cause of disease,while pre-pathology and pre-degeneration dysfunctions have been largely observed in clinical and pre-clinical settings.In addition,it has been reported that unspecific boosting of autophagy can be detrimental.Thus,it is important to understand the mechanisms of specific autophagy forms and,even more,the adjustment of specific lysosome functionalities.Indeed,lysosomes ex
基金supported by the National Natural Science Foundation of China(42177254)Science and Technology Planning Project of Guangdong Province(2020B1212030008)。
文摘N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine quinone(6PPDQ)has attracted significant attention due to its highly acute lethality to sensitive salmonids.However,studies investigating the mechanisms underlying its acute toxicity have been lacking.In this work,we demonstrated the sensitivity of rainbow trout to 6PPDQ-induced mortality.Moribund trout exhibited significantly higher brain concentrations of 6PPDQ compared to surviving trout.In an in vitro model using human brain microvascular endothelial cells,6PPDQ can penetrate the blood–brain barrier and enhance blood–brain barrier permeability without compromising cell viability.The time spent in the top of the tank increased with rising6PPDQ concentrations,as indicated by locomotion behavior tests.Furthermore,6PPDQ influenced neurotransmitter levels and m RNA expression of neurotransmission-related genes in the brain and exhibited strong binding affinity to target neurotransmission-related proteins using computational simulations.The integrated biomarker response value associated with neurotoxicity showed a positive linear correlation with trout mortality.These findings significantly contribute to filling the knowledge gap between neurological impairments and apical outcomes,including behavioral effects and mortality,induced by6PPDQ.
基金supported by the National Natural Science Foundation of China,No.H0906-C090201a grant from the National Science and Technology Support Program of China,No.3G013F843428
文摘Cortical spreading depression is a technique used to depolarize neurons. During focal or global ischemia, cortical spreading depression-induced preconditioning can enhance tolerance of further injury. However, the underlying mechanism for this phenomenon remains relatively unclear. To date, numerous issues exist regarding the experimental model used to precondition the brain with cortical spreading depression, such as the administration route, concentration of potassium chloride, induction time, duration of the protection provided by the treatment, the regional distribution of the protective effect, and the types of neurons responsible for the greater tolerance. In this review, we focus on the mechanisms underlying cor- tical spreading depression-induced tolerance in the brain, considering excitatory neurotransmission and metabolism, nitric oxide, genomic reprogramming, inflammation, neurotropic factors, and cellular stress response. Specifically, we clarify the procedures and detailed information regarding cortical spreading depression-induced preconditioning and build a foundation for more comprehensive investigations in the field of neural regeneration and clinical application in the future.
文摘The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.
文摘目的:探索前列腺Cajal间质细胞(interstitial cells of Cajal,ICCs)与交感神经及平滑肌细胞之间的形态及功能学联系。方法:(1)制作豚鼠前列腺组织冰冻切片并进行双重免疫荧光染色。使用酪氨酸激酶受体(c-Kit)作为ICCs的标记物,酪氨酸羟化酶(tyrosine hydroxylase,TH)和多巴胺β羟化酶(dopamineβ-hydroxylase,DβH)作为交感神经纤维的标记物,α肌动蛋白(α-actin)作为平滑肌细胞的标记物。另外,分别对α1-肾上腺素受体与c-Kit以及缝隙连接蛋白Connexin43(Cx43)与c-Kit进行免疫荧光双重标记。(2)将前列腺肌条固定于灌流槽中,记录去甲肾上腺素(norepinephrine,NE)诱发的肌条收缩幅度和频率,以及加入Glivec后肌条收缩幅度和频率的变化。结果:(1)免疫荧光组织化学标记结果显示:ICCs与交感神经纤维、平滑肌细胞平行分布,ICCs边缘与交感神经、平滑肌细胞边缘密切接触,c-Kit标记的ICCs上存在α1-肾上腺素受体和缝隙连接蛋白Cx43的共表达。(2)在去甲肾上腺素的刺激下前列腺平滑肌肌条收缩幅度为(0.98±0.16)g,收缩频率为(2.54±0.28)次/min。使用Glivec后肌条收缩幅度显著下降,50μmol/L组为(0.56±0.07)g(P<0.01),200μmol/L组为(0.25±0.05)g(P<0.01),收缩频率未见明显改变,50μmol/L组为(2.67±0.32)次/min(P>0.05),200μmol/L组为(2.75±0.31)次/min(P>0.05)。结论:豚鼠前列腺ICCs具有介导前列腺交感神经信号,支配平滑肌活动的形态和功能学基础。
基金supported by the National Nature Science Foundation of China(Grants 81974533,81530098).
文摘Hepatic encephalopathy is a serious neuropsychiatric complication caused by liver failure,which is characterized by the development of cognitive and motor disorders into coma.Typically,hepatic encephalopathy can be divided into three types(A,B,and C)according to the etiology.Type A hepatic encephalopathy(AHE)caused by acute liver failure seriously affects the prognosis of patients,ranging from mild neuropsychological changes to coma,brain edema,and even death.So far,the research on the pathogenesis of AHE has focused on the toxic effects of ammonia on the central nervous system,metabolic disorders(glutamine and lactate accumulation),neurotransmission alteration,systemic inflammation,especially neuro-inflammation.All these mechanisms are not independent,but mutually have synergistic effects.In clinic,treatment of AHE based on only one mechanism is often ineffective.To clarify the pathogenesis and the interaction among the mechanisms will be beneficial to the effective treatment of AHE and reduce the mortality.The aim of this review is to provide comprehensive scientific evidence for the clinical treatment of AHE via collecting and analyzing the latest mechanism of AHE,and clarifying the relationship among these mechanisms combing the investigation of the latest research progress of drug treatment of acute liver failure.Consequently,we find that the pathogenesis of AHE is a complex neurocognitive disorder shaped by interactions among hyperammonemia,inflammation,and changes in neurotransmission,the signaling pathways thereby integrating the inflammatory and neurological inputs to impact pathophysiological or neurobehavioral outcomes.
文摘目的观察黄芩素对阿尔茨海默病(AD)大鼠发病早期认知功能和皮层、海马组织蛋白表达谱的影响,探讨其作用机制。方法实验大鼠随机分为对照组、模型组、黄芩素组,每组12只。黄芩素组大鼠予黄芩素药液灌胃,模型组和对照组大鼠予等量生理盐水灌胃。灌胃体积均为2 m L,连续10 d。利用Morris水迷宫评估治疗效果,并运用双向凝胶电泳技术对脑组织蛋白进行分离,考马斯蓝染显色,应用PDQuest8.0软件对双向电泳图谱进行差异分析,通过MALDI-TOF-MS/MS和数据库查询鉴定差异明显的蛋白质点,并利用String在线分析软件对差异表达蛋白进行生物信息学分析。结果黄芩素可显著缓解β-淀粉样蛋白(Aβ)1-40导致的认知功能减退。黄芩素作用下,位于大鼠大脑皮层和海马组织的8种蛋白表达水平变化明显。质谱鉴定结果显示,差异蛋白涉及4种生物学功能,与神经传导关系最为密切,其中3种蛋白与其他蛋白存在相互作用关系。结论黄芩素对AD大鼠早期认知功能损伤的改善作用与其能够调节神经传导相关蛋白的表达相关。
基金the Florence University(No.RTD CO 090101010107 RICATEN14)Fondazione CRF(No.2017.0777)
文摘AIM To investigate whether the adipocytes derived hormone adiponectin(ADPN) affects the mechanical responses in strips from the mouse gastric fundus. METHODS For functional experiments, gastric strips from the fundal region were cut in the direction of the longitudinal muscle layer and placed in organ baths containing KrebsHenseleit solution. Mechanical responses were recorded via force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrical field stimulation(EFS) was applied via two platinum wire rings through which the preparation was threaded. The effects of ADPN were investigated on the neurally-induced contractile and relaxant responses elicited by EFS. The expression of ADPN receptors, Adipo-R1 and Adipo-R2, was also evaluated by touchdown-PCR analysis. RESULTS In the functional experiments, EFS(4-16 Hz) elicited tetrodotoxin(TTX)-sensitive contractile responses. Addition of ADPN to the bath medium caused a reduction in amplitude of the neurally-induced contractile responses(P < 0.05). The effects of ADPN were no longer observed in the presence of the nitric oxide(NO) synthesis inhibitor L-NG-nitro arginine(L-NNA)(P > 0.05). The direct smooth muscle response to methacholine was not influenced by ADPN(P > 0.05). In carbachol precontracted strips and in the presence of guanethidine, EFS induced relaxant responses. Addition of ADPN to the bath medium, other than causing a slight and progressive decay of the basal tension, increased the amplitude of the neurally-induced relaxant responses(P < 0.05). Touchdown-PCR analysis revealed the expression of both Adipo-R1 and Adipo-R2 in the gastric fundus.CONCLUSION The results indicate for the first time that ADPN is able to influence the mechanical responses in strips from the mouse gastric fundus.
基金This work was supported by the National Natural Sciences Foundation of China(Grant No.30200080)the Ministry of Science and Technology of China(Grant No.2002CCA01000)the Ministry of Education of China(Grant No.02170).
文摘Establishment of animal models of schizophrenia is critical for both understanding the mechanisms underlying this severe mental disease and developing new antipsychotics. This paper starts from the theoretical root of sensory gating, the 損rotection-of-processing?theory, then thoroughly describes the representative studies over the past decade on the mechanism underlying prepulse inhibition and on those underlying modulation of prepulse inhibition, which is the normal startle suppression caused by the weak stimulus preceding the intense startling stimulus. The main methods for inducing prepulse inhibition deficits in experimental animals include: ⅰ) modulations of neuro- transmission that are closely associated with schizophrenia; ⅱ) focal lesions or pharmacological manipulations of brain structures in the cortico-striato-pallido-pontine circuit; and ⅲ) maternal deprivation or social isolation. Six essential topics for studies in modeling schizophrenia are suggested at the last part of this review.
基金The authors of this review were supported by the National Natural Science Foundation of China(81971201)the National Science Foundation of Hunan Province(2019J40450).
文摘In recent years,many studies have investigated the correlations between Parkinson's disease(PD)and vitamin D status,but the conclusion remains elusive.The present review focuses on the associations between PD and serum vitamin D levels by reviewing studies on the associations of PD with serum vitamin D levels and vitamin D receptor(VDR)gene polymorphisms from PubMed,Web of Science,Cochrane Library,and Embase databases.We found that PD patients have lower vitamin D levels than healthy controls and that the vitamin D concentrations are negatively correlated with PD risk and severity.Furthermore,higher vitamin D concentrations are linked to better cognitive function and mood in PD patients.Findings on the relationship between VDR gene polymorphisms and the risk of PD are inconsistent,but the Fokl(C/M)polymorphism is significantly linked with PD.The occurrence of Fokl(CT)gene polymorphism may influence the risk,severity,and cognitive ability of PD patients,while also possibly influencing the effect of Vitamin D3 supplementation in PD patients.In view of the neuroprotective effects of vitamin D and the close association between vitamin D and dopaminergic neurotransmission,interventional prospective studies on vitamin D supplementation in PD patients should be conducted in the future.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 81171053）.
文摘Background Neuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters, which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters （inhibitory GABA transporters GAT and excitatory glutamate transporters GT）. Neuronal hyper-excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission. SNAP-25, which is one of the SNARE complexes, can modulate the release of neurotransmitters. Glia glutamate transporter （GLT） is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS. The role of SNAP-25 and GLT as well as GAT is not clearly understood.
