Neurons can be abstractly represented as skeletons due to the filament nature of neurites.With the rapid development of imaging and image analysis techniques,an increasing amount of neuron skeleton data is being produ...Neurons can be abstractly represented as skeletons due to the filament nature of neurites.With the rapid development of imaging and image analysis techniques,an increasing amount of neuron skeleton data is being produced.In some scienti fic studies,it is necessary to dissect the axons and dendrites,which is typically done manually and is both tedious and time-consuming.To automate this process,we have developed a method that relies solely on neuronal skeletons using Geometric Deep Learning(GDL).We demonstrate the effectiveness of this method using pyramidal neurons in mammalian brains,and the results are promising for its application in neuroscience studies.展开更多
OBJECTIVE Takeda G protein-coupled receptor 5(TGR5)is recognized as a promising target for type 2 diabetes and metabolic syndrome;its expression has been demonstrat⁃ed in the brain and is thought to be neuroprotec⁃tiv...OBJECTIVE Takeda G protein-coupled receptor 5(TGR5)is recognized as a promising target for type 2 diabetes and metabolic syndrome;its expression has been demonstrat⁃ed in the brain and is thought to be neuroprotec⁃tive.Here,we hypothesize that dysfunction of central TGR5 may contribute to the pathogene⁃sis of depression.METHODS In well-established chronic social defeat stress(CSDS)and chronic restraint stress(CRS)models of depression,we investigated the functional roles of TGR5 in CA3 pyramidal neurons(PyNs)and underlying mech⁃anisms of the neuronal circuit in depression(for in vivo studies,n=10;for in vitro studies,n=5-10)using fiber photometry;optogenetic,chemoge⁃netic,pharmacological,and molecular profiling techniques;and behavioral tests.RESULTS Both CSDS and CRS most significantly reduced TGR5 expression of hippocampal CA3 PyNs.Genetic overexpression of TGR5 in CA3 PyNs or intra-CA3 infusion of INT-777,a specific agonist,protected against CSDS and CRS,exerting sig⁃nificant antidepressant-like effects that were mediated via CA3 PyN activation.Conversely,genetic knockout or TGR5 knockdown in CA3 facilitated stress-induced depression-like behav⁃iors.Re-expression of TGR5 in CA3 PyNs rather than infusion of INT-777 significantly improved depression-like behaviors in Tgr5 knockout mice exposed to CSDS or CRS.Silencing and stimula⁃tion of CA3 PyNs→somatostatin-GABAergic(gamma-aminobutyric acidergic)neurons of the dorsolateral septum circuit bidirectionally regulat⁃ed depression-like behaviors,and blockade of this circuit abrogated the antidepressant-like effects from TGR5 activation of CA3 PyNs.CON⁃CLUSION TGR5 can regulate depression via CA3 PyNs→somatostatin-GABAergic neurons of dorsolateral septum transmission,suggesting that TGR5 could be a novel target for developing antidepressants.展开更多
Subjective tinnitus is the most common type of tinnitus, which is the manifestation of pathologicalactivities in the brain. It happens in a substantial portion of the general population and brings significantburden to...Subjective tinnitus is the most common type of tinnitus, which is the manifestation of pathologicalactivities in the brain. It happens in a substantial portion of the general population and brings significantburden to the society. Severe subjective tinnitus can lead to depression and insomnia and severely affectspatients’ quality of life. However, due to poor understanding of its etiology and pathogenesis, treatmentof subjective tinnitus remains challenging. In recent decades, a growing number of studies have shownthat subjective tinnitus is related to lesion-induced neural plasticity of auditory and non-auditory centralsystems. This article reviews cellular mechanisms of neural plasticity in subjective tinnitus to providefurther understanding of its pathogenesis.展开更多
BACKGROUND： Exhaustive exercise can lead to apoptosis of skeletal muscle cells and myocardial cells as a result of pathological changes in the corresponding cellular ultrastructure. It is hypothesized that such chang...BACKGROUND： Exhaustive exercise can lead to apoptosis of skeletal muscle cells and myocardial cells as a result of pathological changes in the corresponding cellular ultrastructure. It is hypothesized that such changes could also occur in neurons. OBJECTIVE： To observe brain cell apoptosis and ultrastructural changes in hippocampal neurons in rats following endurance training and acute exhaustive exercise. DESIGN, TIME AND SETTING： A randomized, controlled, morphological analysis was performed at the Medical Laboratory Center of Zhengzhou University between July and November 2007. MATERIALS： Forty male, 8-week-old, Sprague Dawley rats were included in this study. METHODS： Endurance training consisted of treadmill running once a day, 6 days a week, for 4. weeks. For acute exhaustive exercise, graded treadmill running was conducted. Rats were exposed to exercise at an increasing speed （10 m/min, increasing to 20 and 36 m/min for moderate- and high-intensity exhaustive exercise, respectively, and then was continued until exhaustion）. A total of 40 rats were evenly distributed into the following 4. groups： Group A rats were not exercised; Group B rats were not trained but sacrificed 24 hours after acute exhaustive treadmill running exercise; Group C-rats were subjected to endurance training and sacrificed immediately after acute exhaustive treadmill running exercise; Group D rats were subjected to endurance training and sacrificed 24 hours after acute exhaustive treadmill running exercise. MAIN OUTCOME MEASURES： Apoptotic cell death was detected by the TUNEL method and hippocampal neuronal ultrastructural change was observed through using transmission electron microscopy. RESULTS： All 40 rats were included in the final analysis. Subsequent to exhaustive exercise, rat cerebral cortex and hippocampal neurons appeared contracted and degenerated. In addition, high amount of lipofuscin was visible in the hippocampal region, Necrotic neurons encased by glial cells appeared in the cerebral cortex and hip展开更多
基金supported by the Simons Foundation,the National Natural Science Foundation of China(No.NSFC61405038)the Fujian provincial fund(No.2020J01453).
文摘Neurons can be abstractly represented as skeletons due to the filament nature of neurites.With the rapid development of imaging and image analysis techniques,an increasing amount of neuron skeleton data is being produced.In some scienti fic studies,it is necessary to dissect the axons and dendrites,which is typically done manually and is both tedious and time-consuming.To automate this process,we have developed a method that relies solely on neuronal skeletons using Geometric Deep Learning(GDL).We demonstrate the effectiveness of this method using pyramidal neurons in mammalian brains,and the results are promising for its application in neuroscience studies.
文摘OBJECTIVE Takeda G protein-coupled receptor 5(TGR5)is recognized as a promising target for type 2 diabetes and metabolic syndrome;its expression has been demonstrat⁃ed in the brain and is thought to be neuroprotec⁃tive.Here,we hypothesize that dysfunction of central TGR5 may contribute to the pathogene⁃sis of depression.METHODS In well-established chronic social defeat stress(CSDS)and chronic restraint stress(CRS)models of depression,we investigated the functional roles of TGR5 in CA3 pyramidal neurons(PyNs)and underlying mech⁃anisms of the neuronal circuit in depression(for in vivo studies,n=10;for in vitro studies,n=5-10)using fiber photometry;optogenetic,chemoge⁃netic,pharmacological,and molecular profiling techniques;and behavioral tests.RESULTS Both CSDS and CRS most significantly reduced TGR5 expression of hippocampal CA3 PyNs.Genetic overexpression of TGR5 in CA3 PyNs or intra-CA3 infusion of INT-777,a specific agonist,protected against CSDS and CRS,exerting sig⁃nificant antidepressant-like effects that were mediated via CA3 PyN activation.Conversely,genetic knockout or TGR5 knockdown in CA3 facilitated stress-induced depression-like behav⁃iors.Re-expression of TGR5 in CA3 PyNs rather than infusion of INT-777 significantly improved depression-like behaviors in Tgr5 knockout mice exposed to CSDS or CRS.Silencing and stimula⁃tion of CA3 PyNs→somatostatin-GABAergic(gamma-aminobutyric acidergic)neurons of the dorsolateral septum circuit bidirectionally regulat⁃ed depression-like behaviors,and blockade of this circuit abrogated the antidepressant-like effects from TGR5 activation of CA3 PyNs.CON⁃CLUSION TGR5 can regulate depression via CA3 PyNs→somatostatin-GABAergic neurons of dorsolateral septum transmission,suggesting that TGR5 could be a novel target for developing antidepressants.
基金This work was supported by the National Natural Science Foundation of China under Grant[81820108009]Beijing Municipal Science and Technology Commission under Grant[Z161100000116038]+3 种基金Beijing Municipal Health Commission under Grant[2016-1-5014]Beijing Nova Program[Z201100006820133]the National Key Research and Development Project[2019YFC0121302]the National Key Research and Development Project[2019YFC0840707].
文摘Subjective tinnitus is the most common type of tinnitus, which is the manifestation of pathologicalactivities in the brain. It happens in a substantial portion of the general population and brings significantburden to the society. Severe subjective tinnitus can lead to depression and insomnia and severely affectspatients’ quality of life. However, due to poor understanding of its etiology and pathogenesis, treatmentof subjective tinnitus remains challenging. In recent decades, a growing number of studies have shownthat subjective tinnitus is related to lesion-induced neural plasticity of auditory and non-auditory centralsystems. This article reviews cellular mechanisms of neural plasticity in subjective tinnitus to providefurther understanding of its pathogenesis.
文摘BACKGROUND： Exhaustive exercise can lead to apoptosis of skeletal muscle cells and myocardial cells as a result of pathological changes in the corresponding cellular ultrastructure. It is hypothesized that such changes could also occur in neurons. OBJECTIVE： To observe brain cell apoptosis and ultrastructural changes in hippocampal neurons in rats following endurance training and acute exhaustive exercise. DESIGN, TIME AND SETTING： A randomized, controlled, morphological analysis was performed at the Medical Laboratory Center of Zhengzhou University between July and November 2007. MATERIALS： Forty male, 8-week-old, Sprague Dawley rats were included in this study. METHODS： Endurance training consisted of treadmill running once a day, 6 days a week, for 4. weeks. For acute exhaustive exercise, graded treadmill running was conducted. Rats were exposed to exercise at an increasing speed （10 m/min, increasing to 20 and 36 m/min for moderate- and high-intensity exhaustive exercise, respectively, and then was continued until exhaustion）. A total of 40 rats were evenly distributed into the following 4. groups： Group A rats were not exercised; Group B rats were not trained but sacrificed 24 hours after acute exhaustive treadmill running exercise; Group C-rats were subjected to endurance training and sacrificed immediately after acute exhaustive treadmill running exercise; Group D rats were subjected to endurance training and sacrificed 24 hours after acute exhaustive treadmill running exercise. MAIN OUTCOME MEASURES： Apoptotic cell death was detected by the TUNEL method and hippocampal neuronal ultrastructural change was observed through using transmission electron microscopy. RESULTS： All 40 rats were included in the final analysis. Subsequent to exhaustive exercise, rat cerebral cortex and hippocampal neurons appeared contracted and degenerated. In addition, high amount of lipofuscin was visible in the hippocampal region, Necrotic neurons encased by glial cells appeared in the cerebral cortex and hip
