Denervation often results in skeletal muscle atrophy.Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy.At the epigenetic level,mi RNAs are thought t...Denervation often results in skeletal muscle atrophy.Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy.At the epigenetic level,mi RNAs are thought to be highly involved in the pathophysiological progress of denervated muscles.We used mi RNA microarrays to determine mi RNA expression profiles from a typical slow muscle（soleus muscle） and a typical fast muscle（tibialis anterior muscle） at an early denervation stage in a rat model.Results showed that mi R-206,mi R-195,mi R-23 a,and mi R-30 e might be key factors in the transformation process from slow to fast muscle in denervated slow muscles.Additionally,certain mi RNA molecules（mi R-214,mi R-221,mi R-222,mi R-152,mi R-320,and Let-7e） could be key regulatory factors in the denervated atrophy process involved in fast muscle.Analysis of signaling pathway networks revealed the mi RNA molecules that were responsible for regulating certain signaling pathways,which were the final targets（e.g.,p38 MAPK pathway; Pax3/Pax7 regulates Utrophin and follistatin by HDAC4; IGF1/PI3K/Akt/m TOR pathway regulates atrogin-1 and Mu RF1 expression via Fox O phosphorylation）.Our results provide a better understanding of the mechanisms of denervated skeletal muscle pathophysiology.展开更多
Orthodontic pain is an inflammatory pain that is initiated by orthodontic force-induced vascular occlusion followed by a cascade of inflammatory responses, including vascular changes, the recruitment of inflammatory a...Orthodontic pain is an inflammatory pain that is initiated by orthodontic force-induced vascular occlusion followed by a cascade of inflammatory responses, including vascular changes, the recruitment of inflammatory and immune cells, and the release of neurogenic and pro-inflammatory mediators. Ultimately, endogenous analgesic mechanisms check the inflammatory response and the sensation of pain subsides. The orthodontic pain signal, once received by periodontal sensory endings, reaches the sensory cortex for pain perception through three-order neurons： the trigeminal neuron at the trigeminal ganglia, the trigeminal nucleus caudalis at the medulla oblongata and the ventroposterior nucleus at the thalamus. Many brain areas participate in the emotion, cognition and memory of orthodontic pain, including the insular cortex, amygdala, hippocampus, locus coeruleus and hypothalamus. A built-in analgesic neural pathway--periaqueductal grey and dorsal raphe---has an important role in alleviating orthodontic pain. Currently, several treatment modalities have been applied for the relief of orthodontic pain, including pharmacological, mechanical and behavioural approaches and low-level laser therapy. The effectiveness of nonsteroidal anti- inflammatory drugs for pain relief has been validated, but its effects on tooth movement are controversial. However, more studies are needed to verify the effectiveness of other modalities. Furthermore, gene therapy is a novel, viable and promising modality for alleviatin~ orthodontic oain in the future.展开更多
Due to the complex circuitry and plethora of cell types involved in somatosensation, it is becoming increasingly important to be able to observe cellular activity at the population level. In addition, since cells rely...Due to the complex circuitry and plethora of cell types involved in somatosensation, it is becoming increasingly important to be able to observe cellular activity at the population level. In addition, since cells rely on an intricate variety of extracellular factors, it is important to strive to maintain the physiological environment. Many electrophysiological techniques require the implementation of artificially-produced physiological environments and it can be difficult to assess the activity of many cells simultane- ously. Moreover, imaging Ca^2＋ transients using Ca^2＋- sensitive dyes often requires in vitro preparations or in vivo injections, which can lead to variable expression levels. With the development of more sensitive geneticallyencoded Ca^2＋ indicators （GECIs） it is now possible to observe changes in Ca^2＋ transients in large populations of cells at the same time. Recently, groups have used a GECI called GCaMP to address fundamental questions in somatosensation. Researchers can now induce GCaMP expression in the mouse genome using viral or gene knock- in approaches and observe the activity of populations of cells in the pain pathway such as dorsal root ganglia （DRG）, spinal neurons, or glia. This approach can be used in vivo and thus maintains the organism＇s biological integrity. The implementation of GCaMP imaging has led to many advances in our understanding of somatosensation. Here, we review the current findings in pain research using GCaMP imaging as well as discussing potential method- ological considerations.展开更多
Claudin 14 has been shown to promote nerve repair and regeneration in the early stages of Wallerian degeneration （0-4 days） in rats with sciatic nerve injury, but the mechanism underlying this process remains poorly...Claudin 14 has been shown to promote nerve repair and regeneration in the early stages of Wallerian degeneration （0-4 days） in rats with sciatic nerve injury, but the mechanism underlying this process remains poorly understood. This study reported the effects of claudin 14 on nerve degeneration and regeneration during early Wallerian degeneration. Claudin 14 expression was up-regulated in sciatic nerve 4 days after Wallerian degeneration. The altered expression of claudin 14 in Schwann cells resulted in expression changes of cytokines in vitro. Expression of claudin 14 affected c-Jun, but not Akt anal ERK1/2 patl^ways, l^urther studies reve^ed that enhanced expression of claudin 14 could promote Schwann cell proliferation and migration. Silencing of claudin 14 expression resulted in Schwann cell apoptosis and reduction in Schwann cell proliferation. Our data revealed the role of claudin 14 in early Wallerian degeneration, which may provide new insights into the molecular mechanisms of Wallerian degeneration.展开更多
Psychiatric disorders arc highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points toward D1SCI being one of the genes that i...Psychiatric disorders arc highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points toward D1SCI being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain.展开更多
目的利用纤维束自动定量法探讨高血压对脑白质微结构的影响及其与认知功能的相关性。方法连续性收集2017年1月至2018年7月于南京大学医学院附属鼓楼医院就诊的受试者,分为不伴认知损害的高血压组(hypertension without cognitive impair...目的利用纤维束自动定量法探讨高血压对脑白质微结构的影响及其与认知功能的相关性。方法连续性收集2017年1月至2018年7月于南京大学医学院附属鼓楼医院就诊的受试者,分为不伴认知损害的高血压组(hypertension without cognitive impairment,HTN-nonCI;n=44)、伴认知损害的高血压组(hypertension with cognitive impairment,HTN-CI;n=50)及对照组(n=25)。收集受试者影像学资料及神经心理学量表测试结果,采用纤维束自动定量法得到全脑20条纤维束上各100个节点的弥散参数,比较对照组与HTN-nonCI组以及HTN-nonCI与HTN-CI组各纤维束弥散参数的差异性节段,对HTN-nonCI组与HTN-CI组具有显著差异的脑白质纤维束与各认知域进行相关性分析。结果三组脑白质纤维束的各向异性分数(fractional anisotropy,FA)均呈递减趋势,平均扩散系数(mean diffusivity,MD)均呈递增趋势。对对照组与HTN-nonCI组进行的比较显示,左侧丘脑放射束中点偏脑干侧、胼胝体膝部近脑干侧、胼胝体压部额部及近侧脑室处的FA值差异有统计学意义(P均<0.05);左侧丘脑放射束中部及近脑干部、右侧丘脑放射束近脑干部、左侧皮质脊髓束顶部及近脑干部、右侧扣带束海马中部、胼胝体膝部中部、胼胝体压部近侧脑室处、左侧钩束近额部的MD值差异有统计学意义(P均<0.05)。对HTN-nonCI组与HTN-CI组进行的比较显示,左侧扣带束扣带回的散在分布节段和左侧下额枕束近枕叶侧的FA值差异有统计学意义,其中左侧扣带束扣带回与蒙特利尔认知评估量表评分显著相关(标化β=0.268,P=0.029);右侧丘脑放射束近脑干部、胼胝体压部额部及近侧脑室处、右侧下纵束的散在分布节段的MD值差异有统计学意义,其中右侧下纵束与记忆力(标化β=-0.243,P=0.047)及执行功能(标化β=-0.284,P=0.021)显著相关。结论高血压患者普遍存在脑白质微结构完整性破坏,但部分节段更易受�展开更多
Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target no...Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target novel cellular and molecular mechanisms and mechanisms of action. Increasing evidence suggests that axon guidance molecules play a role in the structural and functional modifications of neural networks and that the dysregulation of these molecules is associated with epilepsy susceptibility. In this review, we discuss the essential role of axon guidance molecules in neuronal activity in patients with epilepsy as well as the impact of these molecules on synaptic plasticity and brain tissue remodeling. Furthermore, we examine the relationship between axon guidance molecules and neuroinflammation, as well as the structural changes in specific brain regions that contribute to the development of epilepsy. Ample evidence indicates that axon guidance molecules, including semaphorins and ephrins, play a fundamental role in guiding axon growth and the establishment of synaptic connections. Deviations in their expression or function can disrupt neuronal connections, ultimately leading to epileptic seizures. The remodeling of neural networks is a significant characteristic of epilepsy, with axon guidance molecules playing a role in the dynamic reorganization of neural circuits. This, in turn, affects synapse formation and elimination. Dysregulation of these molecules can upset the delicate balance between excitation and inhibition within a neural network, thereby increasing the risk of overexcitation and the development of epilepsy. Inflammatory signals can regulate the expression and function of axon guidance molecules, thus influencing axonal growth, axon orientation, and synaptic plasticity. The dysregulation of neuroinflammation can intensify neuronal dysfunction and contribute to the occurrence of epilepsy. This review delves into the mechanisms associated with the pathogenicity of axon guidance molecules in 展开更多
脑小血管病(cerebral small vessel disease, CSVD)是老年人群认知功能下降的主要原因。神经影像学研究表明,CSVD患者存在结构和功能连接异常,且与认知损害相关。因此推测,结构和功能连接改变可能是CSVD相关认知损害的早期影像学标志物...脑小血管病(cerebral small vessel disease, CSVD)是老年人群认知功能下降的主要原因。神经影像学研究表明,CSVD患者存在结构和功能连接异常,且与认知损害相关。因此推测,结构和功能连接改变可能是CSVD相关认知损害的早期影像学标志物。文章就结构和功能连接在CSVD相关认知损害中的意义进行了综述。展开更多
基金supported by the National Natural Science Foundation of China,No.81101365,81171722 and 81000805
文摘Denervation often results in skeletal muscle atrophy.Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy.At the epigenetic level,mi RNAs are thought to be highly involved in the pathophysiological progress of denervated muscles.We used mi RNA microarrays to determine mi RNA expression profiles from a typical slow muscle（soleus muscle） and a typical fast muscle（tibialis anterior muscle） at an early denervation stage in a rat model.Results showed that mi R-206,mi R-195,mi R-23 a,and mi R-30 e might be key factors in the transformation process from slow to fast muscle in denervated slow muscles.Additionally,certain mi RNA molecules（mi R-214,mi R-221,mi R-222,mi R-152,mi R-320,and Let-7e） could be key regulatory factors in the denervated atrophy process involved in fast muscle.Analysis of signaling pathway networks revealed the mi RNA molecules that were responsible for regulating certain signaling pathways,which were the final targets（e.g.,p38 MAPK pathway; Pax3/Pax7 regulates Utrophin and follistatin by HDAC4; IGF1/PI3K/Akt/m TOR pathway regulates atrogin-1 and Mu RF1 expression via Fox O phosphorylation）.Our results provide a better understanding of the mechanisms of denervated skeletal muscle pathophysiology.
基金supported by the National Natural Science Foundation of China (81571004, 81500884 and 81400549)the Orthodontic National Key Clinical Specialty Construction Program of China, West China Hospital of Stomatology, Sichuan University
文摘Orthodontic pain is an inflammatory pain that is initiated by orthodontic force-induced vascular occlusion followed by a cascade of inflammatory responses, including vascular changes, the recruitment of inflammatory and immune cells, and the release of neurogenic and pro-inflammatory mediators. Ultimately, endogenous analgesic mechanisms check the inflammatory response and the sensation of pain subsides. The orthodontic pain signal, once received by periodontal sensory endings, reaches the sensory cortex for pain perception through three-order neurons： the trigeminal neuron at the trigeminal ganglia, the trigeminal nucleus caudalis at the medulla oblongata and the ventroposterior nucleus at the thalamus. Many brain areas participate in the emotion, cognition and memory of orthodontic pain, including the insular cortex, amygdala, hippocampus, locus coeruleus and hypothalamus. A built-in analgesic neural pathway--periaqueductal grey and dorsal raphe---has an important role in alleviating orthodontic pain. Currently, several treatment modalities have been applied for the relief of orthodontic pain, including pharmacological, mechanical and behavioural approaches and low-level laser therapy. The effectiveness of nonsteroidal anti- inflammatory drugs for pain relief has been validated, but its effects on tooth movement are controversial. However, more studies are needed to verify the effectiveness of other modalities. Furthermore, gene therapy is a novel, viable and promising modality for alleviatin~ orthodontic oain in the future.
基金supported by grants from the National Institutes of Health to X.D.(RO1DE022750 and ROINS054791)
文摘Due to the complex circuitry and plethora of cell types involved in somatosensation, it is becoming increasingly important to be able to observe cellular activity at the population level. In addition, since cells rely on an intricate variety of extracellular factors, it is important to strive to maintain the physiological environment. Many electrophysiological techniques require the implementation of artificially-produced physiological environments and it can be difficult to assess the activity of many cells simultane- ously. Moreover, imaging Ca^2＋ transients using Ca^2＋- sensitive dyes often requires in vitro preparations or in vivo injections, which can lead to variable expression levels. With the development of more sensitive geneticallyencoded Ca^2＋ indicators （GECIs） it is now possible to observe changes in Ca^2＋ transients in large populations of cells at the same time. Recently, groups have used a GECI called GCaMP to address fundamental questions in somatosensation. Researchers can now induce GCaMP expression in the mouse genome using viral or gene knock- in approaches and observe the activity of populations of cells in the pain pathway such as dorsal root ganglia （DRG）, spinal neurons, or glia. This approach can be used in vivo and thus maintains the organism＇s biological integrity. The implementation of GCaMP imaging has led to many advances in our understanding of somatosensation. Here, we review the current findings in pain research using GCaMP imaging as well as discussing potential method- ological considerations.
基金supported by grants from the National Natural Science Foundation of China,Grant No.81370982,31170946Key Program,Grant No.81130080+1 种基金the Scientific Research Foundation for Returned Scholars,Ministry of Education of Chinathe Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Claudin 14 has been shown to promote nerve repair and regeneration in the early stages of Wallerian degeneration （0-4 days） in rats with sciatic nerve injury, but the mechanism underlying this process remains poorly understood. This study reported the effects of claudin 14 on nerve degeneration and regeneration during early Wallerian degeneration. Claudin 14 expression was up-regulated in sciatic nerve 4 days after Wallerian degeneration. The altered expression of claudin 14 in Schwann cells resulted in expression changes of cytokines in vitro. Expression of claudin 14 affected c-Jun, but not Akt anal ERK1/2 patl^ways, l^urther studies reve^ed that enhanced expression of claudin 14 could promote Schwann cell proliferation and migration. Silencing of claudin 14 expression resulted in Schwann cell apoptosis and reduction in Schwann cell proliferation. Our data revealed the role of claudin 14 in early Wallerian degeneration, which may provide new insights into the molecular mechanisms of Wallerian degeneration.
文摘Psychiatric disorders arc highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points toward D1SCI being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain.
文摘目的利用纤维束自动定量法探讨高血压对脑白质微结构的影响及其与认知功能的相关性。方法连续性收集2017年1月至2018年7月于南京大学医学院附属鼓楼医院就诊的受试者,分为不伴认知损害的高血压组(hypertension without cognitive impairment,HTN-nonCI;n=44)、伴认知损害的高血压组(hypertension with cognitive impairment,HTN-CI;n=50)及对照组(n=25)。收集受试者影像学资料及神经心理学量表测试结果,采用纤维束自动定量法得到全脑20条纤维束上各100个节点的弥散参数,比较对照组与HTN-nonCI组以及HTN-nonCI与HTN-CI组各纤维束弥散参数的差异性节段,对HTN-nonCI组与HTN-CI组具有显著差异的脑白质纤维束与各认知域进行相关性分析。结果三组脑白质纤维束的各向异性分数(fractional anisotropy,FA)均呈递减趋势,平均扩散系数(mean diffusivity,MD)均呈递增趋势。对对照组与HTN-nonCI组进行的比较显示,左侧丘脑放射束中点偏脑干侧、胼胝体膝部近脑干侧、胼胝体压部额部及近侧脑室处的FA值差异有统计学意义(P均<0.05);左侧丘脑放射束中部及近脑干部、右侧丘脑放射束近脑干部、左侧皮质脊髓束顶部及近脑干部、右侧扣带束海马中部、胼胝体膝部中部、胼胝体压部近侧脑室处、左侧钩束近额部的MD值差异有统计学意义(P均<0.05)。对HTN-nonCI组与HTN-CI组进行的比较显示,左侧扣带束扣带回的散在分布节段和左侧下额枕束近枕叶侧的FA值差异有统计学意义,其中左侧扣带束扣带回与蒙特利尔认知评估量表评分显著相关(标化β=0.268,P=0.029);右侧丘脑放射束近脑干部、胼胝体压部额部及近侧脑室处、右侧下纵束的散在分布节段的MD值差异有统计学意义,其中右侧下纵束与记忆力(标化β=-0.243,P=0.047)及执行功能(标化β=-0.284,P=0.021)显著相关。结论高血压患者普遍存在脑白质微结构完整性破坏,但部分节段更易受�
基金supported by the National Natural Science Foundation of China,Nos. 81760247, 82171450the Scientific Research Foundation for Doctors of the Affiliated Hospital of Zunyi Medical University,No.(2016)14 (all to HH)。
文摘Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target novel cellular and molecular mechanisms and mechanisms of action. Increasing evidence suggests that axon guidance molecules play a role in the structural and functional modifications of neural networks and that the dysregulation of these molecules is associated with epilepsy susceptibility. In this review, we discuss the essential role of axon guidance molecules in neuronal activity in patients with epilepsy as well as the impact of these molecules on synaptic plasticity and brain tissue remodeling. Furthermore, we examine the relationship between axon guidance molecules and neuroinflammation, as well as the structural changes in specific brain regions that contribute to the development of epilepsy. Ample evidence indicates that axon guidance molecules, including semaphorins and ephrins, play a fundamental role in guiding axon growth and the establishment of synaptic connections. Deviations in their expression or function can disrupt neuronal connections, ultimately leading to epileptic seizures. The remodeling of neural networks is a significant characteristic of epilepsy, with axon guidance molecules playing a role in the dynamic reorganization of neural circuits. This, in turn, affects synapse formation and elimination. Dysregulation of these molecules can upset the delicate balance between excitation and inhibition within a neural network, thereby increasing the risk of overexcitation and the development of epilepsy. Inflammatory signals can regulate the expression and function of axon guidance molecules, thus influencing axonal growth, axon orientation, and synaptic plasticity. The dysregulation of neuroinflammation can intensify neuronal dysfunction and contribute to the occurrence of epilepsy. This review delves into the mechanisms associated with the pathogenicity of axon guidance molecules in
文摘脑小血管病(cerebral small vessel disease, CSVD)是老年人群认知功能下降的主要原因。神经影像学研究表明,CSVD患者存在结构和功能连接异常,且与认知损害相关。因此推测,结构和功能连接改变可能是CSVD相关认知损害的早期影像学标志物。文章就结构和功能连接在CSVD相关认知损害中的意义进行了综述。
