The cholinergic system is involved in a broad spectrum of brain function, and its failure has been implicated in Alzheimer＇s disease. Acetylcholine transduces signals through muscarinic and nicotinic acetylcholine re...The cholinergic system is involved in a broad spectrum of brain function, and its failure has been implicated in Alzheimer＇s disease. Acetylcholine transduces signals through muscarinic and nicotinic acetylcholine receptors, both of which influence synaptic plasticity and cognition. However, the mechanisms that relate the rapid gating of nicotinic acetylcholine receptors to persistent changes in brain function have remained elusive. Recent evidence indicates that nicotinic acetylcholine receptors activities affect synaptic morphology and density, which result in persistent rearrangements of neural connectivity. Further investigations of the relationships between nicotinic acetylcholine receptors and rearrangements of neural circuitry in the central nervous system may help understand the pathogenesis of Alzheimer＇s disease.展开更多
The peptide Ser-Phe-Gly-Asp-Ile(SFGDI),derived from sea cucumber,has demonstrated neuroprotective effects in cell models;however,the in vivo neuroprotective efficacy of SFGDI remains unexplored.In this study,we utiliz...The peptide Ser-Phe-Gly-Asp-Ile(SFGDI),derived from sea cucumber,has demonstrated neuroprotective effects in cell models;however,the in vivo neuroprotective efficacy of SFGDI remains unexplored.In this study,we utilized a cognitive disorder mouse model induced by scopolamine and observed that daily oral administration of SFGDI at a dosage of 40 mg/kg resulted in improved behavioral performance in the Passive avoidance test,the Channel-type water maze test,and the Novel object recognition test(P<0.05).Furthermore,our investigation into the underlying neuroprotective mechanisms of SFGDI revealed that it reduced oxidative stress levels through the activation of the Sirt3/SOD/ROS pathway,thereby balancing hippocampal unsaturated lipids(P<0.05)in the mouse hippocampus.Moreover,SFGDI significantly decreased hippocampal neuroinflammation by modu-lating the activation of microglia and hypertrophy of astrocytes.Additionally,SFGDI was found to enhance synaptic plasticity in the mouse hippocampus by activating the ChAT/p-CaMKII/BDNF pathway and increasing spine density in neuron cells(P<0.05),particularly mushroom spines(P<0.05).These experiments demon-strate that SFGDI exhibits neuroprotective effects by regulating hippocampal oxidative stress through the Sirt3/SOD/ROS pathway and synaptic plasticity via the ChAT/p-CaMKII/BDNF pathway in the mouse hippocampus,thus emerging as a potential neuro-nutraceutical agent for alleviating memory impairment.展开更多
Dear Editor,The Shank gene family(SHANK1,SHANK2,and SHANK3)comprises high-risk genetic contributors to autism spectrum disorders(ASD)(Durand et al.,2007;Monteiro and Feng,2017).Copy-number variants and truncating muta...Dear Editor,The Shank gene family(SHANK1,SHANK2,and SHANK3)comprises high-risk genetic contributors to autism spectrum disorders(ASD)(Durand et al.,2007;Monteiro and Feng,2017).Copy-number variants and truncating mutations in these genes have been identi ed in~1%of ASD patients(Leblond et al.,2014;Moessner et al.,2007).Research in Shank-de cient mouse models demonstrates that restoring Shank expression in adulthood can enhance synaptic protein levels,correct defects in synaptic morphology and function,and improve ASDrelated behavioral de cits(Guo et al.,2019;Mei et al.,2016).These ndings suggest that targeting the postsynaptic function of SHANK proteins may be a promising therapeutic strategy for ASD.展开更多
基金supported by the Takeda Science Foundation and JSPS KAKENHI Grant Number 19590247
文摘The cholinergic system is involved in a broad spectrum of brain function, and its failure has been implicated in Alzheimer＇s disease. Acetylcholine transduces signals through muscarinic and nicotinic acetylcholine receptors, both of which influence synaptic plasticity and cognition. However, the mechanisms that relate the rapid gating of nicotinic acetylcholine receptors to persistent changes in brain function have remained elusive. Recent evidence indicates that nicotinic acetylcholine receptors activities affect synaptic morphology and density, which result in persistent rearrangements of neural connectivity. Further investigations of the relationships between nicotinic acetylcholine receptors and rearrangements of neural circuitry in the central nervous system may help understand the pathogenesis of Alzheimer＇s disease.
基金supported by the National Key Research and Devel-opment Program of China(2017YFD0400500)the Graduate Inno-vation Fund of Dalian Polytechnic University.
文摘The peptide Ser-Phe-Gly-Asp-Ile(SFGDI),derived from sea cucumber,has demonstrated neuroprotective effects in cell models;however,the in vivo neuroprotective efficacy of SFGDI remains unexplored.In this study,we utilized a cognitive disorder mouse model induced by scopolamine and observed that daily oral administration of SFGDI at a dosage of 40 mg/kg resulted in improved behavioral performance in the Passive avoidance test,the Channel-type water maze test,and the Novel object recognition test(P<0.05).Furthermore,our investigation into the underlying neuroprotective mechanisms of SFGDI revealed that it reduced oxidative stress levels through the activation of the Sirt3/SOD/ROS pathway,thereby balancing hippocampal unsaturated lipids(P<0.05)in the mouse hippocampus.Moreover,SFGDI significantly decreased hippocampal neuroinflammation by modu-lating the activation of microglia and hypertrophy of astrocytes.Additionally,SFGDI was found to enhance synaptic plasticity in the mouse hippocampus by activating the ChAT/p-CaMKII/BDNF pathway and increasing spine density in neuron cells(P<0.05),particularly mushroom spines(P<0.05).These experiments demon-strate that SFGDI exhibits neuroprotective effects by regulating hippocampal oxidative stress through the Sirt3/SOD/ROS pathway and synaptic plasticity via the ChAT/p-CaMKII/BDNF pathway in the mouse hippocampus,thus emerging as a potential neuro-nutraceutical agent for alleviating memory impairment.
基金supported by grants from the National Natural Science Foundation of China(NSFC)(32330038,32394030)the Ministry of Science and Technology(STI2030-2021ZD0202300)。
文摘Dear Editor,The Shank gene family(SHANK1,SHANK2,and SHANK3)comprises high-risk genetic contributors to autism spectrum disorders(ASD)(Durand et al.,2007;Monteiro and Feng,2017).Copy-number variants and truncating mutations in these genes have been identi ed in~1%of ASD patients(Leblond et al.,2014;Moessner et al.,2007).Research in Shank-de cient mouse models demonstrates that restoring Shank expression in adulthood can enhance synaptic protein levels,correct defects in synaptic morphology and function,and improve ASDrelated behavioral de cits(Guo et al.,2019;Mei et al.,2016).These ndings suggest that targeting the postsynaptic function of SHANK proteins may be a promising therapeutic strategy for ASD.
