Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiet...Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety.However,the underlying mechanism remains unclear.In this study,we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors.We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion.We found that unlike in humans,the combination of harmonic tones and vibrations did not improve anxietylike behaviors in mice,while individual vibration components did.Additionally,the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice,decreased the level ofγ-aminobutyric acid A(GABA)receptorα1 subtype,reduced the level of CaMKII in the prefrontal cortex,and increased the number of GABAergic interneurons.At the same time,electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation.Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.展开更多
Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive ...Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive functioning.Executive functions help us plan,organize,and control our actions based on our goals.The brain area responsible for executive functions is called the prefrontal co rtex.It acts as the command center for the brain,especially when it comes to regulating executive functions.The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine.However,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s disease.In this article,the authors review the latest research on this topic.They start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive dysfunction.Then,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal cortex.The authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive issues.This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.展开更多
Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the pr...Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.展开更多
Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and cortex.Patients can present with a variety of symptoms that can broadly be classified into motor symptoms...Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and cortex.Patients can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive decline.The causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.展开更多
Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and...Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.展开更多
Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-met...Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.展开更多
Stroke is a physiological alteration associated with changes in blood flow that can result in sudden-onset cognitive impairment. It has a heterogenous clinical presentation with varying degrees of severity correlated ...Stroke is a physiological alteration associated with changes in blood flow that can result in sudden-onset cognitive impairment. It has a heterogenous clinical presentation with varying degrees of severity correlated with specific central nervous system zones or areas, and its prognosis is uncertain. This case study describes a 62-year-old male patient with acquired brain damage of the anterior cingulate cortex as a result of an ischemic event in the territory of the left anterior cerebral artery. Cognitive function was assessed using the neuropsychological executive function and frontal lobe test battery (BANFE-2) as well as other neuropsychological tests. The results show a profile of higher mental functions characterized by the presence of dysexecutive syndrome with marked behavioral alteration and diencephalic amnesia. .展开更多
针对采用控制器局域网络(CAN:Controller Area Network)总线的自动操舵系统和采用串口通讯的航海导航设备之间通讯的不匹配问题,设计了一种基于Cortex-M3嵌入式平台的通信转换模块,实现了串口与CAN总线数据的双向转换功能。同时对传统CA...针对采用控制器局域网络(CAN:Controller Area Network)总线的自动操舵系统和采用串口通讯的航海导航设备之间通讯的不匹配问题,设计了一种基于Cortex-M3嵌入式平台的通信转换模块,实现了串口与CAN总线数据的双向转换功能。同时对传统CAN收发器CTM1050存在的信号稳定性不足、波特率精准度低等问题,提出并实现了一种硬件电路的替代方案,提高了数据通讯的时效性和稳定性。基于CAN2.0B扩展帧,设计了自动操舵系统内部CAN总线协议。该协议可根据报文信息优先级分配标识帧,保证了总线数据的有序传输。实验结果表明,该通讯模块功能使用正常且通讯效果良好,具有一定通用性,可在多种需要转换的设备系统上推广使用。展开更多
Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases.Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral org...Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases.Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral organoids,we interrogated the cis-regulatory activity of 102,767 open chromatin regions,including thousands of sequences with cell type-specific accessibility and variants associated with brain gene regulation.In primary cells,we identified 46,802 active enhancer sequences and 164 variants that alter enhancer activity.Activity was comparable in organoids and primary cells,suggesting that organoids provide an adequate model for the developing cortex.Using deep learning we decoded the sequence basis and upstream regulators of enhancer activity.This work establishes a comprehensive catalog of functional gene regulatory elements and variants in human neuronal development.展开更多
Background: Transcranial direct current stimulation (tDCS) across cortical brain areas appears to improve various forms of pain, yet evidence of tDCS efficiency and ideal stimulation target is lacking. This study aime...Background: Transcranial direct current stimulation (tDCS) across cortical brain areas appears to improve various forms of pain, yet evidence of tDCS efficiency and ideal stimulation target is lacking. This study aimed to compare the add-on analgesic efficacy of concentric electrode transcranial direct current stimulation (CE-tDCS) stimulation over the primary motor cortex versus the insular cortex on the management of chronic postmastectomy pain. Method: Prospective randomized double-blind sham-controlled study enrolled eighty patients with chronic postmastectomy pain that were randomly assigned to four groups: active motor (AM), sham motor (SM), active insula (AI) and sham insula (SI) group, each received 5 sessions for 20-minute duration with 2 mA tDCS over the targeted area of the contralateral side of pain. Our primary outcome was VAS score, the secondary outcomes were VDS score, LANSS score and depression symptoms by HAM-D scores, assessment was done at 4 time points (prestimulation, after 5<sup>th</sup> session, 15<sup>th</sup> day and one month after the last session). Results: Both active tDCS groups (motor and insula) showed reduction of VAS (P Conclusion: Active tDCS stimulation either targeting the primary motor cortex or the insula cortex has add-on analgesic effect for controlling neuropathic chronic post mastectomy pain and the maximum effect was at 15 days after the last session.展开更多
The adult cortex has long been regarded as non-neurogenic.Whether injury can induce neurogenesis in the adult cortex is still controversial.Here,we report that focal ischemia stimulates a transient wave of local neuro...The adult cortex has long been regarded as non-neurogenic.Whether injury can induce neurogenesis in the adult cortex is still controversial.Here,we report that focal ischemia stimulates a transient wave of local neurogenesis.Using 5′-bromo-2′-deoxyuridine labeling,we demonstrated a rapid generation of doublecortin-positive neuroblasts that died quickly in mouse cerebral cortex following ischemia.Nestin-Cre^(ER)-based cell ablation and fate mapping showed a small contribution of neuroblasts by subventricular zone neural stem cells.Using a mini-photothrombotic ischemia mouse model and retrovirus expressing green fluorescent protein labeling,we observed maturation of locally generated new neurons.Furthermore,fate tracing analyses using PDGFRα-,GFAP-,and Sox2-Cre^(ER) mice showed a transient wave of neuroblast generation in mild ischemic cortex and identified that Sox2-positive astrocytes were the major neurogenic cells in adult cortex.In addition,a similar upregulation of Sox2 and appearance of neuroblasts were observed in the focal ischemic cortex of Macaca mulatta.Our findings demonstrated a transient neurogenic response of Sox2-positive astrocytes in ischemic cortex,which suggests the possibility of inducing neuronal regeneration by amplifying this intrinsic response in the future.展开更多
基金supported by the National Natural Science Foundation of ChinaNos.32170950(to LY),31970915(to LY),31871170(to CL)+4 种基金the Natural Science Foundation of Guangdong Province for Major Cultivation ProjectNo.2018B030336001(to LY)the Natural Science Foundation of Guangdong Province,Nos.2021A1515010804(to CL),2023A1515010899(to CL)the Guangdong Grant‘Key Technologies for Treatment of Brain Disorders’No.2018B030332001(to CL)。
文摘Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety.However,the underlying mechanism remains unclear.In this study,we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors.We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion.We found that unlike in humans,the combination of harmonic tones and vibrations did not improve anxietylike behaviors in mice,while individual vibration components did.Additionally,the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice,decreased the level ofγ-aminobutyric acid A(GABA)receptorα1 subtype,reduced the level of CaMKII in the prefrontal cortex,and increased the number of GABAergic interneurons.At the same time,electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation.Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.
基金supported by the National Natural Science Foundation of China,No.82101263Jiangsu Province Science Foundation for Youths,No.BK20210903Research Foundation for Talented Scholars of Xuzhou Medical University,No.RC20552114(all to CT)。
文摘Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive functioning.Executive functions help us plan,organize,and control our actions based on our goals.The brain area responsible for executive functions is called the prefrontal co rtex.It acts as the command center for the brain,especially when it comes to regulating executive functions.The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine.However,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s disease.In this article,the authors review the latest research on this topic.They start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive dysfunction.Then,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal cortex.The authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive issues.This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.
基金supported by the STI 2030-Major Projects 2022ZD0208500(to DY)the National Natural Science Foundation of China,Nos.82072011(to YX),82121003(to DY),82271120(to YS)+2 种基金Sichuan Science and Technology Program,No.2022ZYD0066(to YS)a grant from Chinese Academy of Medical Science,No.2019-12M-5-032(to YS)the Fundamental Research Funds for the Central Universities,No.ZYGX2021YGLH219(to KC)。
文摘Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.
文摘Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and cortex.Patients can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive decline.The causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.
基金supported by the National Natural Science Foundation of China,Nos.62027812(to HS),81771470(to HS),and 82101608(to YL)Tianjin Postgraduate Research and Innovation Project,No.2020YJSS122(to XD)。
文摘Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.
基金supported by the National Natural Science Foundation of China,Nos.82030071 (to JH),82272495 (to YC)Science and Technology Major Project of Changsha,No.kh2103008 (to JH)Graduate Students’ Independent Innovative Projects of Hunan Province,No.CX20230311 (to YJ)。
文摘Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.
文摘Stroke is a physiological alteration associated with changes in blood flow that can result in sudden-onset cognitive impairment. It has a heterogenous clinical presentation with varying degrees of severity correlated with specific central nervous system zones or areas, and its prognosis is uncertain. This case study describes a 62-year-old male patient with acquired brain damage of the anterior cingulate cortex as a result of an ischemic event in the territory of the left anterior cerebral artery. Cognitive function was assessed using the neuropsychological executive function and frontal lobe test battery (BANFE-2) as well as other neuropsychological tests. The results show a profile of higher mental functions characterized by the presence of dysexecutive syndrome with marked behavioral alteration and diencephalic amnesia. .
文摘针对采用控制器局域网络(CAN:Controller Area Network)总线的自动操舵系统和采用串口通讯的航海导航设备之间通讯的不匹配问题,设计了一种基于Cortex-M3嵌入式平台的通信转换模块,实现了串口与CAN总线数据的双向转换功能。同时对传统CAN收发器CTM1050存在的信号稳定性不足、波特率精准度低等问题,提出并实现了一种硬件电路的替代方案,提高了数据通讯的时效性和稳定性。基于CAN2.0B扩展帧,设计了自动操舵系统内部CAN总线协议。该协议可根据报文信息优先级分配标识帧,保证了总线数据的有序传输。实验结果表明,该通讯模块功能使用正常且通讯效果良好,具有一定通用性,可在多种需要转换的设备系统上推广使用。
文摘Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases.Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral organoids,we interrogated the cis-regulatory activity of 102,767 open chromatin regions,including thousands of sequences with cell type-specific accessibility and variants associated with brain gene regulation.In primary cells,we identified 46,802 active enhancer sequences and 164 variants that alter enhancer activity.Activity was comparable in organoids and primary cells,suggesting that organoids provide an adequate model for the developing cortex.Using deep learning we decoded the sequence basis and upstream regulators of enhancer activity.This work establishes a comprehensive catalog of functional gene regulatory elements and variants in human neuronal development.
文摘Background: Transcranial direct current stimulation (tDCS) across cortical brain areas appears to improve various forms of pain, yet evidence of tDCS efficiency and ideal stimulation target is lacking. This study aimed to compare the add-on analgesic efficacy of concentric electrode transcranial direct current stimulation (CE-tDCS) stimulation over the primary motor cortex versus the insular cortex on the management of chronic postmastectomy pain. Method: Prospective randomized double-blind sham-controlled study enrolled eighty patients with chronic postmastectomy pain that were randomly assigned to four groups: active motor (AM), sham motor (SM), active insula (AI) and sham insula (SI) group, each received 5 sessions for 20-minute duration with 2 mA tDCS over the targeted area of the contralateral side of pain. Our primary outcome was VAS score, the secondary outcomes were VDS score, LANSS score and depression symptoms by HAM-D scores, assessment was done at 4 time points (prestimulation, after 5<sup>th</sup> session, 15<sup>th</sup> day and one month after the last session). Results: Both active tDCS groups (motor and insula) showed reduction of VAS (P Conclusion: Active tDCS stimulation either targeting the primary motor cortex or the insula cortex has add-on analgesic effect for controlling neuropathic chronic post mastectomy pain and the maximum effect was at 15 days after the last session.
基金supported by the National Natural Science Foundation of China,Nos.82171346(to YZW)82171269(to JLY)+1 种基金82171471(to HF)Beijing Nova Program,No.Z201100006820076(to JLY).
文摘The adult cortex has long been regarded as non-neurogenic.Whether injury can induce neurogenesis in the adult cortex is still controversial.Here,we report that focal ischemia stimulates a transient wave of local neurogenesis.Using 5′-bromo-2′-deoxyuridine labeling,we demonstrated a rapid generation of doublecortin-positive neuroblasts that died quickly in mouse cerebral cortex following ischemia.Nestin-Cre^(ER)-based cell ablation and fate mapping showed a small contribution of neuroblasts by subventricular zone neural stem cells.Using a mini-photothrombotic ischemia mouse model and retrovirus expressing green fluorescent protein labeling,we observed maturation of locally generated new neurons.Furthermore,fate tracing analyses using PDGFRα-,GFAP-,and Sox2-Cre^(ER) mice showed a transient wave of neuroblast generation in mild ischemic cortex and identified that Sox2-positive astrocytes were the major neurogenic cells in adult cortex.In addition,a similar upregulation of Sox2 and appearance of neuroblasts were observed in the focal ischemic cortex of Macaca mulatta.Our findings demonstrated a transient neurogenic response of Sox2-positive astrocytes in ischemic cortex,which suggests the possibility of inducing neuronal regeneration by amplifying this intrinsic response in the future.