The triple transgenic mouse model of Alzheimer’s disease(3×Tg-AD)is a widely used model that exhibits region-dependent patterns of progressive amyloid-βand tau pathology.Although structural brain abnormalities ...The triple transgenic mouse model of Alzheimer’s disease(3×Tg-AD)is a widely used model that exhibits region-dependent patterns of progressive amyloid-βand tau pathology.Although structural brain abnormalities on magnetic resonance imaging have been observed in 3×Tg-AD mice at later disease stages(>12 months)and as early as 2 months,few studies have investigated changes in these mice during the stage with extensive amyloid-βdeposition and onset of tau pathology(around 9 months).This study aimed to assess brain morphometry and microstructure alterations in 9 month-old 3×Tg-AD mice to better understand the neural mechanisms underlying these specific pathological features.Voxel-based analyses were employed on T2-weighted and diffusion tensor imaging to identify differences between 3×Tg-AD and control mice.Compared with controls,3×Tg-AD mice exhibited lower gray matter volume in several regions including both hippocampal regions,the right thalamus,the left caudoputamen,and the cortex.Reduced white matter volume was observed in fiber tracts including the corpus callosum,internal capsule,stria terminalis,and olfactory tract.Whole-brain diffusion tensor imaging analysis revealed a significant decrease in fractional anisotropy and an increase in both radial and mean diffusivity within the left dentate gyrus of the hippocampal region and right striatum-like amygdala nuclei,with no significant difference in axial diffusivity.Correlation analyses demonstrated significant associations between behavioral performance measures,with both gray and white matter volumes within regions showing significant morphometric differences.Notably,behavioral performance also exhibited significant correlations with diffusion tensor imaging measures particularly within the left dentate gyrus of the hippocampal region and right striatum-like amygdala nuclei.Immunofluorescence analysis confirmed increased amyloid-βplaques and p-Tau protein expression in the hippocampal regions of 3×Tg-AD mice,which corroborated the magnetic resonance imaging findings.Transcriptome analysis in hippocampus tissue identified 1389 differentially expressed genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that numerous differentially expressed genes were enriched in biological processes relevant to synapse structure,cognition,learning,and memory,with particular emphasis on Wnt and mitogen-activated protein kinase signaling pathways.Collectively,these findings suggest that intricate anatomical and microstructural alterations occur in 3×Tg-AD model mice at the onset of pathology around 9 months,potentially driven by gene expression alterations.Moreover,our results support the potential utility of brain volume and diffusion metrics as biomarkers for Alzheimer’s disease pathology,which could have significant implications for clinical diagnosis of Alzheimer’s disease patients.展开更多
目的:探讨行为激活团体心理治疗改善非典型抑郁症青少年的脑网络特征的效果。方法:纳入2023年7月至2024年7月于我院诊断的非典型抑郁症青少年120例。通过双重差分模型(difference in difference,DID)验证治疗的净效果;分析脑网络拓扑指...目的:探讨行为激活团体心理治疗改善非典型抑郁症青少年的脑网络特征的效果。方法:纳入2023年7月至2024年7月于我院诊断的非典型抑郁症青少年120例。通过双重差分模型(difference in difference,DID)验证治疗的净效果;分析脑网络拓扑指标与生活质量评分、抑郁评分的关联。结果:DID分析显示治疗后研究组的生活质量综合评定问卷(generic quality of life inventory-74,GQOL-74)评分上升幅度及17项汉密尔顿抑郁量表(Hamilton depression scale-17 item,HAMD-17)评分下降幅度均优于对照组(P均<0.001);治疗后对照组脑网络拓扑指标显著高于研究组(P<0.05);不同脑网络拓扑指标对HAMD-17、GQOL-74评分均存在不同程度影响。结论:行为激活团体心理治疗能够显著改善非典型抑郁症青少年的抑郁症状,提升其生活质量,并对脑网络特征产生积极影响。同时脑网络结构与患者生活质量和抑郁程度密切相关。展开更多
基金supported by the National Key R&D Program of China,No.2023YFE0209500(to ZQ)the Natural Science Foundation of Guangdong Province,China,Nos.2023A1515010772(to YL),2025A1515011720(to YL)+1 种基金the Medical Science and Technology Research Foundation of Guangdong Province,No.A2024120(to YL)the National Natural Science Foundation of China,No.U22A20371(to ZQ).
文摘The triple transgenic mouse model of Alzheimer’s disease(3×Tg-AD)is a widely used model that exhibits region-dependent patterns of progressive amyloid-βand tau pathology.Although structural brain abnormalities on magnetic resonance imaging have been observed in 3×Tg-AD mice at later disease stages(>12 months)and as early as 2 months,few studies have investigated changes in these mice during the stage with extensive amyloid-βdeposition and onset of tau pathology(around 9 months).This study aimed to assess brain morphometry and microstructure alterations in 9 month-old 3×Tg-AD mice to better understand the neural mechanisms underlying these specific pathological features.Voxel-based analyses were employed on T2-weighted and diffusion tensor imaging to identify differences between 3×Tg-AD and control mice.Compared with controls,3×Tg-AD mice exhibited lower gray matter volume in several regions including both hippocampal regions,the right thalamus,the left caudoputamen,and the cortex.Reduced white matter volume was observed in fiber tracts including the corpus callosum,internal capsule,stria terminalis,and olfactory tract.Whole-brain diffusion tensor imaging analysis revealed a significant decrease in fractional anisotropy and an increase in both radial and mean diffusivity within the left dentate gyrus of the hippocampal region and right striatum-like amygdala nuclei,with no significant difference in axial diffusivity.Correlation analyses demonstrated significant associations between behavioral performance measures,with both gray and white matter volumes within regions showing significant morphometric differences.Notably,behavioral performance also exhibited significant correlations with diffusion tensor imaging measures particularly within the left dentate gyrus of the hippocampal region and right striatum-like amygdala nuclei.Immunofluorescence analysis confirmed increased amyloid-βplaques and p-Tau protein expression in the hippocampal regions of 3×Tg-AD mice,which corroborated the magnetic resonance imaging findings.Transcriptome analysis in hippocampus tissue identified 1389 differentially expressed genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that numerous differentially expressed genes were enriched in biological processes relevant to synapse structure,cognition,learning,and memory,with particular emphasis on Wnt and mitogen-activated protein kinase signaling pathways.Collectively,these findings suggest that intricate anatomical and microstructural alterations occur in 3×Tg-AD model mice at the onset of pathology around 9 months,potentially driven by gene expression alterations.Moreover,our results support the potential utility of brain volume and diffusion metrics as biomarkers for Alzheimer’s disease pathology,which could have significant implications for clinical diagnosis of Alzheimer’s disease patients.
文摘目的:探讨行为激活团体心理治疗改善非典型抑郁症青少年的脑网络特征的效果。方法:纳入2023年7月至2024年7月于我院诊断的非典型抑郁症青少年120例。通过双重差分模型(difference in difference,DID)验证治疗的净效果;分析脑网络拓扑指标与生活质量评分、抑郁评分的关联。结果:DID分析显示治疗后研究组的生活质量综合评定问卷(generic quality of life inventory-74,GQOL-74)评分上升幅度及17项汉密尔顿抑郁量表(Hamilton depression scale-17 item,HAMD-17)评分下降幅度均优于对照组(P均<0.001);治疗后对照组脑网络拓扑指标显著高于研究组(P<0.05);不同脑网络拓扑指标对HAMD-17、GQOL-74评分均存在不同程度影响。结论:行为激活团体心理治疗能够显著改善非典型抑郁症青少年的抑郁症状,提升其生活质量,并对脑网络特征产生积极影响。同时脑网络结构与患者生活质量和抑郁程度密切相关。
