Spinal cord injury is a devastating condition that is followed by long and often unsuccessful recovery after trauma. The state of the art approach to manage paralysis and concomitant impairments is rehabilitation, whi...Spinal cord injury is a devastating condition that is followed by long and often unsuccessful recovery after trauma. The state of the art approach to manage paralysis and concomitant impairments is rehabilitation, which is the only strategy that has proven to be effective and beneficial for the patients over the last decades. How rehabilitation influences the remodeling of spinal axonal connections in patients is important to understand, in order to better target these changes and define the optimal timing and onset of training. While clinically the answers to these questions remain difficult to obtain, rodent models of rehabilitation like bicycling, treadmill training, swimming, enriched environments or wheel running that mimic clinical rehabilitation can be helpful to reveal the axonal changes underlying motor recovery. This review will focus on the different animal models of spinal cord injury rehabilitation and the underlying changes in neuronal networks that are improved by exercise and rehabilitation.展开更多
Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia.However,given its inherent complexity,few animal models of delir...Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia.However,given its inherent complexity,few animal models of delirium have been established and the mechanism underlying the onset of delirium remains elusive.Here,we conducted a comparison of three mouse models of delirium induced by clinically relevant risk factors,including anesthesia with surgery(AS),systemic inflammation,and neurotransmission modulation.We found that both bacterial lipopolysaccharide(LPS)and cholinergic receptor antagonist scopolamine(Scop)induction reduced neuronal activities in the delirium-related brain network,with the latter presenting a similar pattern of reduction as found in delirium patients.Consistently,Scop injection resulted in reversible cognitive impairment with hyperactive behavior.No loss of cholinergic neurons was found with treatment,but hippocampal synaptic functions were affected.These findings provide further clues regarding the mechanism underlying delirium onset and demonstrate the successful application of the Scop injection model in mimicking delirium-like phenotypes in mice.展开更多
The prefrontal cortex(PFC)is thought to be involved in higher order cognitive functions,such as in working memory,abstract categorization,and reward processing.It has been reported that two distinct neuron classes(put...The prefrontal cortex(PFC)is thought to be involved in higher order cognitive functions,such as in working memory,abstract categorization,and reward processing.It has been reported that two distinct neuron classes(putative pyramidal cells and interneurons)in the PFC played different functional roles in neural circuits involved in forming working memory and abstract categories.However,it remains elusive how the two types of neurons process reward information in the PFC.To investigate this issue,the activity of single neurons was extracellularly recorded in the PFC of the monkey performing a reward predicting task.PFC neurons were classified into putative pyramidal cells and interneurons,respectively,based on the waveforms of action potentials.Both the two types of neurons encoded reward information and discriminated two reward conditions(the preferred reward condition vs.the nonpreferred reward condition).However,the putative pyramidal neurons had better and more reliable discriminability than the putative interneurons.Also,the pyramidal cells represented reward information in the preferred reward condition,but not in the nonpreferred reward condition by raising their firing rates relative to the baseline rates.In contrast,the interneurons encoded reward information in the nonpreferred reward condition,but not in the preferred reward condition by inhibiting their discharge rates relative to the baseline rates.These results suggested that the putative pyramidal cells and interneurons had complementary functions in reward processing.These findings may help to clarify individual functions of each type of neurons in PFC neuronal circuits involved in reward processing.展开更多
Parkinson’s disease (PD) is a common neurodegenerative disease with unclear pathogenesis. Currently, there are no disease-modifying neuron-protecting drugs to slow down the neuronal degeneration. Mutations in the leu...Parkinson’s disease (PD) is a common neurodegenerative disease with unclear pathogenesis. Currently, there are no disease-modifying neuron-protecting drugs to slow down the neuronal degeneration. Mutations in the leucine-rich repeat kinase 2 (LRRK2) cause genetic forms of PD and contribute to sporadic PD as well. Disruption of LRRK2 kinase functions has become one of the potential mechanisms underlying disease-linked mutation-induced neuronal degeneration. To further characterize the pharmacological effects of a reported LRRK2 kinase inhibitor, LDN-73794, in vitro cell models and a LRRK2 Drosophila PD model were used. LDN-73794 reduced LRRK2 kinase activity in vitro and in vivo. Moreover, LDN-73794 increased survival, improved locomotor activity, and suppressed DA neuron loss in LRRK2 transgenic flies. These results suggest that inhibition of LRRK2 kinase activity can be a potential therapeutic strategy for PD intervention and LDN-73794 could be a potential lead compound for developing neuroprotective therapeutics.展开更多
观察运动疲劳大鼠黑质致密区(substantia nigra zonacompacta,SNc)多巴胺(dopamine,DA)神经元自发放电特征,探讨运动疲劳产生的中枢机制。方法:采用胞外玻璃微电极技术,在体观察运动疲劳后大鼠SNc区DA神经元自发电活动的变化。结果:运...观察运动疲劳大鼠黑质致密区(substantia nigra zonacompacta,SNc)多巴胺(dopamine,DA)神经元自发放电特征,探讨运动疲劳产生的中枢机制。方法:采用胞外玻璃微电极技术,在体观察运动疲劳后大鼠SNc区DA神经元自发电活动的变化。结果:运动疲劳大鼠SNc区DA能神经元自发单放电频率较对照组显著降低,神经元出现了不规则放电,且爆发式放电比例明显增多,放电间隔直方图成正偏态或随机分布(AI<1),ISI和CV值均显著大于对照组。结论:运动疲劳大鼠SNc区DA能神经元电活动出现明显改变,主要特征为兴奋性和活动规律性降低。SNc和纹状体的腹外侧和背外侧区构成的黑质—纹状体DA能神经通路参与了基底神经节对运动的调节,也是运动疲劳调控的重要中枢脑区之一。展开更多
基金Work in FMB laboratory is supported by grants from the Deutsche Forschungsgemeinschaft(DFG,SFB870)by the Munich Center for Neurosciences(MCN)+2 种基金the Wings for Life foundationsupported by the Munich Center for Systems Neurology(DFG,SyNergyEXC 1010)
文摘Spinal cord injury is a devastating condition that is followed by long and often unsuccessful recovery after trauma. The state of the art approach to manage paralysis and concomitant impairments is rehabilitation, which is the only strategy that has proven to be effective and beneficial for the patients over the last decades. How rehabilitation influences the remodeling of spinal axonal connections in patients is important to understand, in order to better target these changes and define the optimal timing and onset of training. While clinically the answers to these questions remain difficult to obtain, rodent models of rehabilitation like bicycling, treadmill training, swimming, enriched environments or wheel running that mimic clinical rehabilitation can be helpful to reveal the axonal changes underlying motor recovery. This review will focus on the different animal models of spinal cord injury rehabilitation and the underlying changes in neuronal networks that are improved by exercise and rehabilitation.
基金supported by the National Natural Science Foundation of China(82071191,82001129)Natural Science Foundation of Sichuan Province(2022NSFSC1509)+1 种基金National Clinical Research Center for Geriatrics of West China Hospital(Z2021LC001)West China Hospital 1.3.5 Project for Disciplines of Excellence(ZYYC20009)。
文摘Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia.However,given its inherent complexity,few animal models of delirium have been established and the mechanism underlying the onset of delirium remains elusive.Here,we conducted a comparison of three mouse models of delirium induced by clinically relevant risk factors,including anesthesia with surgery(AS),systemic inflammation,and neurotransmission modulation.We found that both bacterial lipopolysaccharide(LPS)and cholinergic receptor antagonist scopolamine(Scop)induction reduced neuronal activities in the delirium-related brain network,with the latter presenting a similar pattern of reduction as found in delirium patients.Consistently,Scop injection resulted in reversible cognitive impairment with hyperactive behavior.No loss of cholinergic neurons was found with treatment,but hippocampal synaptic functions were affected.These findings provide further clues regarding the mechanism underlying delirium onset and demonstrate the successful application of the Scop injection model in mimicking delirium-like phenotypes in mice.
基金supported by Grant-in-aid for Scientific Research on Innovative Areas,Grant-in-aid for Scientific Research(A),and Tamagawa Global Center of Excellence,Japanthe National Natural Science Foundation of China(Grant No.11232005)+1 种基金the Fundamental Research Funds for the Central Universities of ChinaShanghai Pujiang Program(Grant No.13PJ1402000)
文摘The prefrontal cortex(PFC)is thought to be involved in higher order cognitive functions,such as in working memory,abstract categorization,and reward processing.It has been reported that two distinct neuron classes(putative pyramidal cells and interneurons)in the PFC played different functional roles in neural circuits involved in forming working memory and abstract categories.However,it remains elusive how the two types of neurons process reward information in the PFC.To investigate this issue,the activity of single neurons was extracellularly recorded in the PFC of the monkey performing a reward predicting task.PFC neurons were classified into putative pyramidal cells and interneurons,respectively,based on the waveforms of action potentials.Both the two types of neurons encoded reward information and discriminated two reward conditions(the preferred reward condition vs.the nonpreferred reward condition).However,the putative pyramidal neurons had better and more reliable discriminability than the putative interneurons.Also,the pyramidal cells represented reward information in the preferred reward condition,but not in the nonpreferred reward condition by raising their firing rates relative to the baseline rates.In contrast,the interneurons encoded reward information in the nonpreferred reward condition,but not in the preferred reward condition by inhibiting their discharge rates relative to the baseline rates.These results suggested that the putative pyramidal cells and interneurons had complementary functions in reward processing.These findings may help to clarify individual functions of each type of neurons in PFC neuronal circuits involved in reward processing.
文摘Parkinson’s disease (PD) is a common neurodegenerative disease with unclear pathogenesis. Currently, there are no disease-modifying neuron-protecting drugs to slow down the neuronal degeneration. Mutations in the leucine-rich repeat kinase 2 (LRRK2) cause genetic forms of PD and contribute to sporadic PD as well. Disruption of LRRK2 kinase functions has become one of the potential mechanisms underlying disease-linked mutation-induced neuronal degeneration. To further characterize the pharmacological effects of a reported LRRK2 kinase inhibitor, LDN-73794, in vitro cell models and a LRRK2 Drosophila PD model were used. LDN-73794 reduced LRRK2 kinase activity in vitro and in vivo. Moreover, LDN-73794 increased survival, improved locomotor activity, and suppressed DA neuron loss in LRRK2 transgenic flies. These results suggest that inhibition of LRRK2 kinase activity can be a potential therapeutic strategy for PD intervention and LDN-73794 could be a potential lead compound for developing neuroprotective therapeutics.
文摘观察运动疲劳大鼠黑质致密区(substantia nigra zonacompacta,SNc)多巴胺(dopamine,DA)神经元自发放电特征,探讨运动疲劳产生的中枢机制。方法:采用胞外玻璃微电极技术,在体观察运动疲劳后大鼠SNc区DA神经元自发电活动的变化。结果:运动疲劳大鼠SNc区DA能神经元自发单放电频率较对照组显著降低,神经元出现了不规则放电,且爆发式放电比例明显增多,放电间隔直方图成正偏态或随机分布(AI<1),ISI和CV值均显著大于对照组。结论:运动疲劳大鼠SNc区DA能神经元电活动出现明显改变,主要特征为兴奋性和活动规律性降低。SNc和纹状体的腹外侧和背外侧区构成的黑质—纹状体DA能神经通路参与了基底神经节对运动的调节,也是运动疲劳调控的重要中枢脑区之一。
基金supported by the Science and Technology Foundation of Education Department of Liaoning ProvinceChina(No.2023101067)+3 种基金the Science and Technology Foundation of Department of Science and TechnologyShenyang MunicipalityChina(No.1022043-1-03F10-205-1-42)
