Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have ...Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in tempo ral lobe epile psy.However,their role in the cognitive impairment of temporal lobe epilepsy remains unclear.In this study,we found that patients with temporal lobe epile psy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory,but had no impairment in nonverbal memory.The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tra cts measured by diffusion tensor imaging.In a mouse model of chronic temporal lobe epilepsy induced by kainic acid,the number of medial septum choline rgic neurons was reduced and acetylcholine release was reduced in the hippocampus.Furthermore,selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice,and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid-and kindling-induced epile psy models.These res ults suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.展开更多
Cholinergic system associated DOPA-refractory motor and cognitive symptoms-a need for novel therapeutic approaches:Accumulating evidence points to significant motor and non-motor morbidities associated with hypocholin...Cholinergic system associated DOPA-refractory motor and cognitive symptoms-a need for novel therapeutic approaches:Accumulating evidence points to significant motor and non-motor morbidities associated with hypocholinergic deficits in central and peripheral neural systems in Parkinson’s disease(PD)(Bohnen et al.,2018,2022).This so-called“malignant”hypocholinergic disease phenotype is associated with DOPA-refractory dementia and mobility disturbances,such as falls and freezing of gait,and augur novel therapeutic approaches targeting cholinergic systems in PD.Cholinergic pharmacotherapy in PD has been an interest for a long time.However,the development of cholinergic augmentation pharmacotherapy has been hampered by limited clinical efficacy,the presumption that changes in cholinergic activity are homogeneous in the central nervous system(CNS)and peripheral nervous system,tolerance or safety of cholinesterase inhibitor drugs,low CNS penetrance,high rate of peripheral autonomic side-effects and clinical contra-indications.The development of nicotinic or muscarinic receptor modulating drugs appears more promising but is still in the development stage.Given the current unmet need for managing DOPA-refractory cognitive and mobility impairments associated with hypocholinergic neural systems,there is a need for novel and complementary therapeutic and more personalized approaches.展开更多
Chrysanthellum americanum (L.) Vatke is a medicinal plant used by the traditional healers to treat epilepsy and associated memory impairment. This work aims at evaluating the anticonvulsant effects of Chrysanthellum a...Chrysanthellum americanum (L.) Vatke is a medicinal plant used by the traditional healers to treat epilepsy and associated memory impairment. This work aims at evaluating the anticonvulsant effects of Chrysanthellum americanum aqueous extract in mice pilocarpine model of epilepsy and associated memory loss. Mice were administered orally Chrysanthellum americanum aqueous extract (27.69, 69.22, 138.45, 276.9 mg/kg, prepared from the whole part) for test groups, intraperitoneally 300 mg/kg sodium valproate for the positive control group or orally 10 mL/kg distilled water for the negative control group, respectively, during a period of seven consecutive days. On the first day, temporal lobe epilepsy was induced by intraperitoneal injection of 360 mg/kg pilocarpine one hour after the administration of different treatment to mice, and the occurrence of status epilepticus was evaluated. On the second day, the anticonvulsant property was measured after the intraperitoneal injection of a sub-convulsive dose of picrotoxin (1 mg/kg). On the seventh day, the anti-amnesic properties of the extract were evaluated in the epileptic mice using the T-maze and open field paradigms. The results show that Chrysanthellum americanum extract significantly (p Chrysanthellum americanum (276.9 mg/kg) likewise sodium valproate (300 mg/kg) significantly (p Chrysanthellum americanum aqueous extract has anticonvulsant effects against pilocarpine induced-epileptic seizures and memory impairment. These properties could be mediated by the amelioration of antioxidant defense system and cholinergic neurotransmission in epileptic mice, which could partly justify the use of Chrysanthellum americanum in the traditional medicine for the treatment of epilepsy.展开更多
The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent bu...The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.展开更多
Myasthenia gravis(MG)is an autoimmune disorder that affects the neuromuscular junction.The primary pathology in MG involves the presence of autoantibodies to acetylcholine receptors(AChRs),which results in qualitative...Myasthenia gravis(MG)is an autoimmune disorder that affects the neuromuscular junction.The primary pathology in MG involves the presence of autoantibodies to acetylcholine receptors(AChRs),which results in qualitative and quantitative reductions in the availability of functional AChRs.Cardiac muscles are also affected,resulting in various perioperative cardiac complications.Antistriational antibodies are commonly reported in MG cases with cardiac involvement.In the presence of thymoma,the prevalence of cardiac manifestations in patients with MG increases to approximately 10%-15%.Cardiac involvement in MG may range from asymptomatic electrocardiogram changes to ventricular tachycardia,myocarditis,conduction disorders,heart failure,and sudden death.Increased incidence of atrial fibrillation,ventricular and supraventricular extra systoles,and prolonged QTc have also been reported in patients with MG.Clinicians should consider the evaluation of autonomic dysfunction and risk of cardiovascular disease in patients with MG.展开更多
Butyrylcholinesterase(BChE;EC 3.1.1.8),an enzyme structurally related to acetylcholinesterase,is widely distributed in the human body.It plays a role in the detoxification of chemicals such as succinylcholine,a muscle...Butyrylcholinesterase(BChE;EC 3.1.1.8),an enzyme structurally related to acetylcholinesterase,is widely distributed in the human body.It plays a role in the detoxification of chemicals such as succinylcholine,a muscle relaxant used in anesthetic practice.BChE is well-known due to variant forms of the enzyme with little or no hydrolytic activity which exist in some endogamous communities and result in prolonged apnea following the administration of succinylcholine.Its other functions include the ability to hydrolyze acetylcholine,the cholinergic neurotransmitter in the brain,when its primary hydrolytic enzyme,acetylcholinesterase,is absent.To assess its potential roles,BChE was studied in relation to insulin resistance,type 2 diabetes mellitus,cognition,hepatic disorders,cardiovascular and cerebrovascular diseases,and inflammatory conditions.Individuals who lack the enzyme activity of BChE are otherwise healthy,until they are given drugs hydrolyzed by this enzyme.Therefore,BChE is a candidate for the study of loss-of-function mutations in humans.Studying individuals with variant forms of BChE can provide insights into whether they are protected against metabolic diseases.The potential utility of the enzyme as a biomarker for Alzheimer’s disease and the response to its drug treatment can also be assessed.展开更多
非痴呆型血管性认知障碍(vascular cognitive impairment no dementia,VCIND)是认知障碍的早期阶段,认知损害尚未达到痴呆的标准。本文从中医“虚、痰、瘀”的病因病机进行阐述,脾肾亏虚为发病基础,痰瘀互结为致病因素,导致髓海不足,清...非痴呆型血管性认知障碍(vascular cognitive impairment no dementia,VCIND)是认知障碍的早期阶段,认知损害尚未达到痴呆的标准。本文从中医“虚、痰、瘀”的病因病机进行阐述,脾肾亏虚为发病基础,痰瘀互结为致病因素,导致髓海不足,清窍失养,发为痴呆。胆碱能通路与认知障碍的发生发展密切相关,包括神经递质乙酰胆碱的缺乏、脑白质病变影响胆碱能通路的网络连接以及胆碱能抗炎通路等。探讨中医虚痰瘀的病机演变与胆碱能通路发病机制之间的关系,有助于进一步发掘中医中药治疗在胆碱能通路的作用。展开更多
基金National Natural Science Foundation of China,Nos.82003 729 (to Ying W),82022071 (to YiW)Natural Science Foundation of Shandong Province of China,No.ZR2020QH357 (to Ying W)Public Welfare Technology Research Program of Zhejiang Province,No.LGF20H09001 1 (to JF)。
文摘Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in tempo ral lobe epile psy.However,their role in the cognitive impairment of temporal lobe epilepsy remains unclear.In this study,we found that patients with temporal lobe epile psy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory,but had no impairment in nonverbal memory.The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tra cts measured by diffusion tensor imaging.In a mouse model of chronic temporal lobe epilepsy induced by kainic acid,the number of medial septum choline rgic neurons was reduced and acetylcholine release was reduced in the hippocampus.Furthermore,selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice,and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid-and kindling-induced epile psy models.These res ults suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.
基金supported by the National Institute of Health,No.P50 NS123067The Farmer Family Foundation+2 种基金supported by the NIHR Newcastle Biomedical Research Centre(BRC)The NIHR BRC is a partnership between Newcastle Hospitals NHS Foundation Trust and Newcastle Universityfunded by the National Institute for Health and Care Research(NIHR)。
文摘Cholinergic system associated DOPA-refractory motor and cognitive symptoms-a need for novel therapeutic approaches:Accumulating evidence points to significant motor and non-motor morbidities associated with hypocholinergic deficits in central and peripheral neural systems in Parkinson’s disease(PD)(Bohnen et al.,2018,2022).This so-called“malignant”hypocholinergic disease phenotype is associated with DOPA-refractory dementia and mobility disturbances,such as falls and freezing of gait,and augur novel therapeutic approaches targeting cholinergic systems in PD.Cholinergic pharmacotherapy in PD has been an interest for a long time.However,the development of cholinergic augmentation pharmacotherapy has been hampered by limited clinical efficacy,the presumption that changes in cholinergic activity are homogeneous in the central nervous system(CNS)and peripheral nervous system,tolerance or safety of cholinesterase inhibitor drugs,low CNS penetrance,high rate of peripheral autonomic side-effects and clinical contra-indications.The development of nicotinic or muscarinic receptor modulating drugs appears more promising but is still in the development stage.Given the current unmet need for managing DOPA-refractory cognitive and mobility impairments associated with hypocholinergic neural systems,there is a need for novel and complementary therapeutic and more personalized approaches.
文摘Chrysanthellum americanum (L.) Vatke is a medicinal plant used by the traditional healers to treat epilepsy and associated memory impairment. This work aims at evaluating the anticonvulsant effects of Chrysanthellum americanum aqueous extract in mice pilocarpine model of epilepsy and associated memory loss. Mice were administered orally Chrysanthellum americanum aqueous extract (27.69, 69.22, 138.45, 276.9 mg/kg, prepared from the whole part) for test groups, intraperitoneally 300 mg/kg sodium valproate for the positive control group or orally 10 mL/kg distilled water for the negative control group, respectively, during a period of seven consecutive days. On the first day, temporal lobe epilepsy was induced by intraperitoneal injection of 360 mg/kg pilocarpine one hour after the administration of different treatment to mice, and the occurrence of status epilepticus was evaluated. On the second day, the anticonvulsant property was measured after the intraperitoneal injection of a sub-convulsive dose of picrotoxin (1 mg/kg). On the seventh day, the anti-amnesic properties of the extract were evaluated in the epileptic mice using the T-maze and open field paradigms. The results show that Chrysanthellum americanum extract significantly (p Chrysanthellum americanum (276.9 mg/kg) likewise sodium valproate (300 mg/kg) significantly (p Chrysanthellum americanum aqueous extract has anticonvulsant effects against pilocarpine induced-epileptic seizures and memory impairment. These properties could be mediated by the amelioration of antioxidant defense system and cholinergic neurotransmission in epileptic mice, which could partly justify the use of Chrysanthellum americanum in the traditional medicine for the treatment of epilepsy.
基金supported by the National Natural Science Foundation of China,No.82071419Key Research and Development Program of Guangzhou,No.202206010086+1 种基金High-level Hospital Construction Project,No.DFJH201907Supporting Research Funds for Outstanding Young Medical Talents in Guangdong Province,No.KJ012019442(all to YZ)。
文摘The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.
文摘Myasthenia gravis(MG)is an autoimmune disorder that affects the neuromuscular junction.The primary pathology in MG involves the presence of autoantibodies to acetylcholine receptors(AChRs),which results in qualitative and quantitative reductions in the availability of functional AChRs.Cardiac muscles are also affected,resulting in various perioperative cardiac complications.Antistriational antibodies are commonly reported in MG cases with cardiac involvement.In the presence of thymoma,the prevalence of cardiac manifestations in patients with MG increases to approximately 10%-15%.Cardiac involvement in MG may range from asymptomatic electrocardiogram changes to ventricular tachycardia,myocarditis,conduction disorders,heart failure,and sudden death.Increased incidence of atrial fibrillation,ventricular and supraventricular extra systoles,and prolonged QTc have also been reported in patients with MG.Clinicians should consider the evaluation of autonomic dysfunction and risk of cardiovascular disease in patients with MG.
文摘Butyrylcholinesterase(BChE;EC 3.1.1.8),an enzyme structurally related to acetylcholinesterase,is widely distributed in the human body.It plays a role in the detoxification of chemicals such as succinylcholine,a muscle relaxant used in anesthetic practice.BChE is well-known due to variant forms of the enzyme with little or no hydrolytic activity which exist in some endogamous communities and result in prolonged apnea following the administration of succinylcholine.Its other functions include the ability to hydrolyze acetylcholine,the cholinergic neurotransmitter in the brain,when its primary hydrolytic enzyme,acetylcholinesterase,is absent.To assess its potential roles,BChE was studied in relation to insulin resistance,type 2 diabetes mellitus,cognition,hepatic disorders,cardiovascular and cerebrovascular diseases,and inflammatory conditions.Individuals who lack the enzyme activity of BChE are otherwise healthy,until they are given drugs hydrolyzed by this enzyme.Therefore,BChE is a candidate for the study of loss-of-function mutations in humans.Studying individuals with variant forms of BChE can provide insights into whether they are protected against metabolic diseases.The potential utility of the enzyme as a biomarker for Alzheimer’s disease and the response to its drug treatment can also be assessed.
文摘非痴呆型血管性认知障碍(vascular cognitive impairment no dementia,VCIND)是认知障碍的早期阶段,认知损害尚未达到痴呆的标准。本文从中医“虚、痰、瘀”的病因病机进行阐述,脾肾亏虚为发病基础,痰瘀互结为致病因素,导致髓海不足,清窍失养,发为痴呆。胆碱能通路与认知障碍的发生发展密切相关,包括神经递质乙酰胆碱的缺乏、脑白质病变影响胆碱能通路的网络连接以及胆碱能抗炎通路等。探讨中医虚痰瘀的病机演变与胆碱能通路发病机制之间的关系,有助于进一步发掘中医中药治疗在胆碱能通路的作用。
