Neurobiology of Aging最新文献

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Age-related differences in long-term memory performance and astrocyte morphology in rat hippocampus

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-02-27 DOI: 10.1016/j.neurobiolaging.2025.02.006

Yandara A. Martins, Camila A.E.F. Cardinali, Andréa S. Torrão

Astrocytes are neuromodulator cells. Their complex and dynamic morphology regulates neuronal signaling, synaptic plasticity, and neurogenesis. The impact of aging on astrocyte morphology is still under ongoing debate. Therefore, this study aimed to characterize astrocyte morphology in the hippocampus of older rats. 2-, 18-, and 20-month-old male Wistar rats were submitted to the object recognition test to assess their short- and long-term memories. CA1, CA2, CA3, and the dentate gyrus were collected for immunohistochemistry analysis and glial fibrillary acid protein (GFAP) immunostaining. Our results indicate that 20-month-old rats did not recognize or discriminate the novel object in the long-term memory test. Also, GFAP staining was greater in the oldest group for all analyzed areas. Morphometric and fractal analysis indicated shorter branch lengths and smaller sizes for astrocytes of 20-month-old rats. Overall, our results suggest that 20-month-old rats have long-term memory impairment, increased GFAP staining, and astrocyte dystrophy. These age-related alterations in astrocyte morphology are a resource for future studies exploring the role of astrocytes in age-related cognitive decline and age-related diseases.

{"title":"Age-related differences in long-term memory performance and astrocyte morphology in rat hippocampus","authors":"Yandara A. Martins, Camila A.E.F. Cardinali, Andréa S. Torrão","doi":"10.1016/j.neurobiolaging.2025.02.006","DOIUrl":"10.1016/j.neurobiolaging.2025.02.006","url":null,"abstract":"<div><div>Astrocytes are neuromodulator cells. Their complex and dynamic morphology regulates neuronal signaling, synaptic plasticity, and neurogenesis. The impact of aging on astrocyte morphology is still under ongoing debate. Therefore, this study aimed to characterize astrocyte morphology in the hippocampus of older rats. 2-, 18-, and 20-month-old male Wistar rats were submitted to the object recognition test to assess their short- and long-term memories. CA1, CA2, CA3, and the dentate gyrus were collected for immunohistochemistry analysis and glial fibrillary acid protein (GFAP) immunostaining. Our results indicate that 20-month-old rats did not recognize or discriminate the novel object in the long-term memory test. Also, GFAP staining was greater in the oldest group for all analyzed areas. Morphometric and fractal analysis indicated shorter branch lengths and smaller sizes for astrocytes of 20-month-old rats. Overall, our results suggest that 20-month-old rats have long-term memory impairment, increased GFAP staining, and astrocyte dystrophy. These age-related alterations in astrocyte morphology are a resource for future studies exploring the role of astrocytes in age-related cognitive decline and age-related diseases.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"150 ","pages":"Pages 19-43"},"PeriodicalIF":3.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CSF α-synuclein aggregation is associated with APOE ε4 and progressive cognitive decline in Alzheimer's disease

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-02-27 DOI: 10.1016/j.neurobiolaging.2025.02.008

Qiang Qiang , Loren Skudder-Hill , Tomoko Toyota , Zhe Huang , Wenshi Wei , Hiroaki Adachi , Alzheimer’s Disease Neuroimaging Initiative

At autopsy, around half of the Alzheimer's disease (AD) brains exhibit Lewy body pathology, and the main component of Lewy body pathology is α-synuclein aggregates. This study investigated the prevalence of cerebrospinal fluid (CSF) α-synuclein aggregation and its association with demographic factors and cognitive decline among 1619 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), with the test for α-synuclein aggregation by seed amplification assay (SAA). This cohort consisted of 595 cognitively normal (CN) individuals, 765 with mild cognitive impairment (MCI), and 259 with AD dementia. The results showed a higher prevalence of positive α-synuclein aggregation status in the AD dementia group (37.07 %) and the MCI group (22.75 %) compared to CN controls (16.13 %). Additionally, APOE ε4 carriers exhibited a higher prevalence of α-synuclein aggregation compared to non-carriers: 20.12 % for APOE ε4-/- (non-carriers), 24.82 % for APOE ε4 + /-, and 30.92 % for APOE ε4 + /+ . Longitudinally, positive CSF α-synuclein aggregation associated with accelerated cognitive decline, especially in the MCI and AD groups. Notably, positive aggregation status did not significantly affect cognitive trajectories in CN individuals. Moreover, APOE ε4 carriers with positive CSF α-synuclein aggregation experienced more pronounced cognitive decline. This study provides evidence that CSF α-synuclein aggregation is associated with cognitive function and the APOE ε4 allele. These findings suggest that CSF α-synuclein SAA, in combination with APOE ε4 status, could serve as biomarkers for predicting cognitive decline in AD.

{"title":"CSF α-synuclein aggregation is associated with APOE ε4 and progressive cognitive decline in Alzheimer's disease","authors":"Qiang Qiang , Loren Skudder-Hill , Tomoko Toyota , Zhe Huang , Wenshi Wei , Hiroaki Adachi , Alzheimer’s Disease Neuroimaging Initiative","doi":"10.1016/j.neurobiolaging.2025.02.008","DOIUrl":"10.1016/j.neurobiolaging.2025.02.008","url":null,"abstract":"<div><div>At autopsy, around half of the Alzheimer's disease (AD) brains exhibit Lewy body pathology, and the main component of Lewy body pathology is α-synuclein aggregates. This study investigated the prevalence of cerebrospinal fluid (CSF) α-synuclein aggregation and its association with demographic factors and cognitive decline among 1619 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), with the test for α-synuclein aggregation by seed amplification assay (SAA). This cohort consisted of 595 cognitively normal (CN) individuals, 765 with mild cognitive impairment (MCI), and 259 with AD dementia. The results showed a higher prevalence of positive α-synuclein aggregation status in the AD dementia group (37.07 %) and the MCI group (22.75 %) compared to CN controls (16.13 %). Additionally, APOE ε4 carriers exhibited a higher prevalence of α-synuclein aggregation compared to non-carriers: 20.12 % for APOE ε4-/- (non-carriers), 24.82 % for APOE ε4 + /-, and 30.92 % for APOE ε4 + /+ . Longitudinally, positive CSF α-synuclein aggregation associated with accelerated cognitive decline, especially in the MCI and AD groups. Notably, positive aggregation status did not significantly affect cognitive trajectories in CN individuals. Moreover, APOE ε4 carriers with positive CSF α-synuclein aggregation experienced more pronounced cognitive decline. This study provides evidence that CSF α-synuclein aggregation is associated with cognitive function and the APOE ε4 allele. These findings suggest that CSF α-synuclein SAA, in combination with APOE ε4 status, could serve as biomarkers for predicting cognitive decline in AD.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"150 ","pages":"Pages 9-18"},"PeriodicalIF":3.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Relation of MRI visible perivascular spaces with global and regional brain structural connectivity measures: The Framingham Heart Study (FHS)

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-02-27 DOI: 10.1016/j.neurobiolaging.2025.02.007

Oluchi Ekenze , Stephan Seiler , Adlin Pinheiro , Charles DeCarli , Pedram Parva , Mohamad Habes , Andreas Charidimou , Pauline Maillard , Alexa Beiser , Sudha Seshadri , Serkalem Demissie , Jose Rafael Romero

MRI visible perivascular spaces (PVS) are associated with cognitive impairment and dementia, which are also associated with disrupted network connectivity. PVS may relate to dementia risk through disruption in brain connectivity. We studied the relation between PVS grade and global and regional structural connectivity in Framingham Heart Study participants free of stroke and dementia. PVS were rated on axial T2 sequences in the basal ganglia (BG) and centrum semiovale (CSO). We assessed structural global and regional network architecture using global efficiency, local efficiency and modularity. Analysis of covariance was used to relate PVS grades with structural network measures. Models adjusted for age, sex (model 1), and vascular risk factors (model 2). Effect modification on the associations by age, sex, hypertension and APOE-ɛ4 status was assessed. Among 2525 participants (mean age 54 ± 13 years, 53 % female), significant associations were observed between grade III and IV PVS in the BG and CSO with reduced global efficiency. Grade III (β −0.0030; 95 % confidence interval [CI] −0.0041, −0.0019) and IV (β −0.0033, CI −0.0060, −0.0007) PVS in the BG and grade IV (β −0.0015; CI −0.0024, −0.0007) PVS in the CSO were associated with reduced local efficiency. We observed shared and different strength of association by age, hypertension, sex and APOE-ɛ4 in the relationship between high burden PVS in the BG and CSO with structural network measures. Findings suggest that higher grade PVS are associated with disruption of global and regional structural brain networks.

{"title":"Relation of MRI visible perivascular spaces with global and regional brain structural connectivity measures: The Framingham Heart Study (FHS)","authors":"Oluchi Ekenze , Stephan Seiler , Adlin Pinheiro , Charles DeCarli , Pedram Parva , Mohamad Habes , Andreas Charidimou , Pauline Maillard , Alexa Beiser , Sudha Seshadri , Serkalem Demissie , Jose Rafael Romero","doi":"10.1016/j.neurobiolaging.2025.02.007","DOIUrl":"10.1016/j.neurobiolaging.2025.02.007","url":null,"abstract":"<div><div>MRI visible perivascular spaces (PVS) are associated with cognitive impairment and dementia, which are also associated with disrupted network connectivity. PVS may relate to dementia risk through disruption in brain connectivity. We studied the relation between PVS grade and global and regional structural connectivity in Framingham Heart Study participants free of stroke and dementia. PVS were rated on axial T2 sequences in the basal ganglia (BG) and centrum semiovale (CSO). We assessed structural global and regional network architecture using global efficiency, local efficiency and modularity. Analysis of covariance was used to relate PVS grades with structural network measures. Models adjusted for age, sex (model 1), and vascular risk factors (model 2). Effect modification on the associations by age, sex, hypertension and APOE-ɛ4 status was assessed. Among 2525 participants (mean age 54 ± 13 years, 53 % female), significant associations were observed between grade III and IV PVS in the BG and CSO with reduced global efficiency. Grade III (β −0.0030; 95 % confidence interval [CI] −0.0041, −0.0019) and IV (β −0.0033, CI −0.0060, −0.0007) PVS in the BG and grade IV (β −0.0015; CI −0.0024, −0.0007) PVS in the CSO were associated with reduced local efficiency. We observed shared and different strength of association by age, hypertension, sex and APOE-ɛ4 in the relationship between high burden PVS in the BG and CSO with structural network measures. Findings suggest that higher grade PVS are associated with disruption of global and regional structural brain networks.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"150 ","pages":"Pages 1-8"},"PeriodicalIF":3.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Editorial Advisory Board

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-02-25 DOI: 10.1016/S0197-4580(25)00031-4

引用次数: 0

Advancing age and sex modulate antidyskinetic efficacy of striatal CaV1.3 gene therapy in a rat model of Parkinson’s disease

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-02-20 DOI: 10.1016/j.neurobiolaging.2025.02.003

Margaret E. Caulfield , Molly J. Vander Werp , Jennifer A. Stancati , Timothy J. Collier , Caryl E. Sortwell , Ivette M. Sandoval , Jeffrey H. Kordower , Fredric P. Manfredsson , Kathy Steece-Collier

We previously demonstrated that viral vector-mediated striatal Ca_V1.3 calcium channel downregulation in young adult (3mo) male parkinsonian rats provides uniform, robust protection against levodopa-induced dyskinesias (LID). Acknowledging the association of PD with aging and incidence in male and female sexes, we have expanded our studies to include rats of advancing age of both sexes. The current study directly contrasts age and sex, determining their impact on efficacy of intrastriatal AAV-Ca_V1.3-shRNA to prevent LID induction, removing the variable of levodopa-priming. Considering both sexes together, late-middle-aged (‘aged’; 15mo) parkinsonian rats receiving AAV-Ca_V1.3-shRNA developed significantly less severe LID compared control AAV-scramble(SCR)-shRNA rats, however therapeutic benefit was significantly less robust than observed in young males. When considered separately, females showed significantly less therapeutic benefit than males. Furthermore, aged non-cycling/proestrous-negative female rats were refractory to LID induction, regardless of vector. This study provides novel insight into the impact of age and sex on the variable antidyskinetic responses of Ca_V1.3-targeted gene therapy, highlighting the importance of including clinically relevant age and sex populations in PD studies.

{"title":"Advancing age and sex modulate antidyskinetic efficacy of striatal CaV1.3 gene therapy in a rat model of Parkinson’s disease","authors":"Margaret E. Caulfield , Molly J. Vander Werp , Jennifer A. Stancati , Timothy J. Collier , Caryl E. Sortwell , Ivette M. Sandoval , Jeffrey H. Kordower , Fredric P. Manfredsson , Kathy Steece-Collier","doi":"10.1016/j.neurobiolaging.2025.02.003","DOIUrl":"10.1016/j.neurobiolaging.2025.02.003","url":null,"abstract":"<div><div>We previously demonstrated that viral vector-mediated striatal Ca<sub>V</sub>1.3 calcium channel downregulation in young adult (3mo) male parkinsonian rats provides uniform, robust protection against levodopa-induced dyskinesias (LID). Acknowledging the association of PD with aging and incidence in male and female sexes, we have expanded our studies to include rats of advancing age of both sexes. The current study directly contrasts age and sex, determining their impact on efficacy of intrastriatal AAV-Ca<sub>V</sub>1.3-shRNA to prevent LID induction, removing the variable of levodopa-priming. Considering both sexes together, late-middle-aged (‘aged’; 15mo) parkinsonian rats receiving AAV-Ca<sub>V</sub>1.3-shRNA developed significantly less severe LID compared control AAV-scramble(SCR)-shRNA rats, however therapeutic benefit was significantly less robust than observed in young males. When considered separately, females showed significantly less therapeutic benefit than males. Furthermore, aged non-cycling/proestrous-negative female rats were refractory to LID induction, regardless of vector. This study provides novel insight into the impact of age and sex on the variable antidyskinetic responses of Ca<sub>V</sub>1.3-targeted gene therapy, highlighting the importance of including clinically relevant age and sex populations in PD studies.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"149 ","pages":"Pages 54-66"},"PeriodicalIF":3.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aging of gray matter microstructure: A brain-wide characterization of, age group differences using NODDI

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-02-19 DOI: 10.1016/j.neurobiolaging.2025.02.004

Danielle Greenman, Ilana J. Bennett

This study aimed to provide a complete characterization of age group differences in cortical lobar, hippocampal, and subcortical gray matter microstructure using a multi-compartment diffusion-weighted MRI (DWI) approach with parameters optimized for gray matter (Neurite Orientation Dispersion and Density Imaging, NODDI). 76 younger (undergraduate students) and 64 older (surrounding communities) adults underwent diffusion-, T1-, and susceptibility-weighted MRI. Results revealed eight unique patterns across the 12 regions of interest in the relative direction and magnitude of age effects across NODDI metrics, which were grouped into three prominent patterns: cortical gray matter had predominantly higher free diffusion in older than younger adults, the hippocampus and amygdala had predominantly higher dispersion of diffusion and intracellular diffusion in older than younger adults, and the putamen and globus pallidus had lower dispersion of diffusion in older than younger adults. Results remained largely unchanged after controlling for normalized regional volume, suggesting that higher free diffusion in older than younger adults in cortical gray matter was not driven by macrostructural atrophy. Results also remained largely unchanged after controlling for iron content (QSM, R₂*), even in iron-rich subcortical regions. Taken together, these patterns of age effects across NODDI metrics provide evidence of region-specific neurobiological substrates of aging of gray matter microstructure.

{"title":"Aging of gray matter microstructure: A brain-wide characterization of, age group differences using NODDI","authors":"Danielle Greenman, Ilana J. Bennett","doi":"10.1016/j.neurobiolaging.2025.02.004","DOIUrl":"10.1016/j.neurobiolaging.2025.02.004","url":null,"abstract":"<div><div>This study aimed to provide a complete characterization of age group differences in cortical lobar, hippocampal, and subcortical gray matter microstructure using a multi-compartment diffusion-weighted MRI (DWI) approach with parameters optimized for gray matter (Neurite Orientation Dispersion and Density Imaging, NODDI). 76 younger (undergraduate students) and 64 older (surrounding communities) adults underwent diffusion-, T1-, and susceptibility-weighted MRI. Results revealed eight unique patterns across the 12 regions of interest in the relative direction and magnitude of age effects across NODDI metrics, which were grouped into three prominent patterns: cortical gray matter had predominantly higher free diffusion in older than younger adults, the hippocampus and amygdala had predominantly higher dispersion of diffusion and intracellular diffusion in older than younger adults, and the putamen and globus pallidus had lower dispersion of diffusion in older than younger adults. Results remained largely unchanged after controlling for normalized regional volume, suggesting that higher free diffusion in older than younger adults in cortical gray matter was not driven by macrostructural atrophy. Results also remained largely unchanged after controlling for iron content (QSM, R<sub>2</sub>*), even in iron-rich subcortical regions. Taken together, these patterns of age effects across NODDI metrics provide evidence of region-specific neurobiological substrates of aging of gray matter microstructure.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"149 ","pages":"Pages 34-43"},"PeriodicalIF":3.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Brain activation in older adults during odor identification is related to ApoE, t-tau/Aβ1–42, and hippocampal volume

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-02-12 DOI: 10.1016/j.neurobiolaging.2025.02.001

Abigail Albertazzi , Claire Murphy

Despite altered odor identification preceding and predicting Alzheimer’s disease (AD) cognitive decline, an inadequate understanding of how AD pathology affects odor memory functions limits its use as a preclinical biomarker. Multivariate linear regression was applied to whole-brain blood-oxygen-level-dependent (BOLD) activations during odor identification task (OID) responses in older adults without dementia (N = 36, 44.4 % ε4 carriers, M_Age= 76.61). Apolipoprotein-E ε4 allele status, cerebrospinal fluid levels of total-tau to Amyloid-β_1–42, and MRI-derived hippocampal volume measures were used as predictors. The predictors described significant BOLD variation in regions that are associated with necessary OID functions and affected by AD neurodegeneration during OID responses; moreover, all predictors were associated with significant (P < .001) negative BOLD effects in essential task regions during at least one response condition. This evidence suggests significant pathological effects of AD biomarkers on OID-response neural activity in older adults without dementia and should motivate future combined-biomarker investigations of OID functions in preclinical populations.

{"title":"Brain activation in older adults during odor identification is related to ApoE, t-tau/Aβ1–42, and hippocampal volume","authors":"Abigail Albertazzi , Claire Murphy","doi":"10.1016/j.neurobiolaging.2025.02.001","DOIUrl":"10.1016/j.neurobiolaging.2025.02.001","url":null,"abstract":"<div><div>Despite altered odor identification preceding and predicting Alzheimer’s disease (AD) cognitive decline, an inadequate understanding of how AD pathology affects odor memory functions limits its use as a preclinical biomarker. Multivariate linear regression was applied to whole-brain blood-oxygen-level-dependent (BOLD) activations during odor identification task (OID) responses in older adults without dementia (<em>N</em> = 36, 44.4 % ε4 carriers, <em>M</em><sub>Age</sub>= 76.61). Apolipoprotein-E ε4 allele status, cerebrospinal fluid levels of total-tau to Amyloid-β<sub>1–42</sub>, and MRI-derived hippocampal volume measures were used as predictors. The predictors described significant BOLD variation in regions that are associated with necessary OID functions and affected by AD neurodegeneration during OID responses; moreover, all predictors were associated with significant (<em>P</em> < .001) negative BOLD effects in essential task regions during at least one response condition. This evidence suggests significant pathological effects of AD biomarkers on OID-response neural activity in older adults without dementia and should motivate future combined-biomarker investigations of OID functions in preclinical populations.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"149 ","pages":"Pages 44-53"},"PeriodicalIF":3.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Normative aging results in degradation of gene networks in a zebra finch basal ganglia nucleus dedicated to vocal behavior

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-02-12 DOI: 10.1016/j.neurobiolaging.2025.02.002

Charles M. Higgins , Sri Harsha Vishwanath , Fiona M. McCarthy , Michelle L. Gordon , Beate Peter , Julie E. Miller

Aging increases brain susceptibility to neurodegenerative diseases, but the mechanisms are not clear. Vocal behavior provides an accessible, reliable, and sensitive biomarker to address this because voice changes in middle age can be early indicators of neurodegenerative diseases. The adult male zebra finch is an excellent model organism for these studies due to well-characterized vocal brain circuitry and strong homology to human brain centers. We performed RNA sequencing of song-dedicated basal ganglia nucleus Area X followed by weighted gene co-expression network analyses to examine changes in gene patterns across younger adult, middle, and older ages. Song-correlated gene networks degrade with age, with modules losing their coherence and migrating to different sets of genes, and changes in connection strength particularly for hub genes including those associated with human speech, Parkinson’s, and Alzheimer’s diseases. Gene pathway enrichment analyses reveal a lack of ongoing metabolic and biogenic processes in older finches. Our findings provide a robust platform for targeting network hubs in the treatment of neurologically driven human vocal disorders.

{"title":"Normative aging results in degradation of gene networks in a zebra finch basal ganglia nucleus dedicated to vocal behavior","authors":"Charles M. Higgins , Sri Harsha Vishwanath , Fiona M. McCarthy , Michelle L. Gordon , Beate Peter , Julie E. Miller","doi":"10.1016/j.neurobiolaging.2025.02.002","DOIUrl":"10.1016/j.neurobiolaging.2025.02.002","url":null,"abstract":"<div><div>Aging increases brain susceptibility to neurodegenerative diseases, but the mechanisms are not clear. Vocal behavior provides an accessible, reliable, and sensitive biomarker to address this because voice changes in middle age can be early indicators of neurodegenerative diseases. The adult male zebra finch is an excellent model organism for these studies due to well-characterized vocal brain circuitry and strong homology to human brain centers. We performed RNA sequencing of song-dedicated basal ganglia nucleus Area X followed by weighted gene co-expression network analyses to examine changes in gene patterns across younger adult, middle, and older ages. Song-correlated gene networks degrade with age, with modules losing their coherence and migrating to different sets of genes, and changes in connection strength particularly for hub genes including those associated with human speech, Parkinson’s, and Alzheimer’s diseases. Gene pathway enrichment analyses reveal a lack of ongoing metabolic and biogenic processes in older finches. Our findings provide a robust platform for targeting network hubs in the treatment of neurologically driven human vocal disorders.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"149 ","pages":"Pages 19-33"},"PeriodicalIF":3.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring morphological and microstructural signatures across the Alzheimer's spectrum and risk factors

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-02-07 DOI: 10.1016/j.neurobiolaging.2025.01.011

Aurélie Bussy , Raihaan Patel , Olivier Parent , Alyssa Salaciak , Saashi A. Bedford , Sarah Farzin , Stephanie Tullo , Cynthia Picard , Sylvia Villeneuve , Judes Poirier , John CS Breitner , Gabriel A. Devenyi , PREVENT-AD Research Group, Christine L. Tardif , M. Mallar Chakravarty

Neural alterations, including myelin degeneration and inflammation-related iron burden, may accompany early Alzheimer's disease (AD) pathophysiology. This study aims to identify multi-modal signatures associated with MRI-derived atrophy and quantitative MRI (qMRI) measures of myelin and iron in a unique dataset of 158 participants across the AD spectrum, including those without cognitive impairment, at familial risk for AD, with mild cognitive impairment, and with AD dementia. Our results revealed a brain pattern with decreased cortical thickness, indicating increased neuronal death, and compromised hippocampal integrity due to reduced myelin content. This pattern was associated with lifestyle factors such as smoking, high blood pressure, high cholesterol, and anxiety, as well as older age, AD progression, and APOE-ɛ4 carrier status. These findings underscore the value of qMRI metrics as a non-invasive tool, offering sensitivity to lifestyle-related modifiable risk factors and medical history, even in preclinical stages of AD.

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引用次数: 0

Age-related synaptic signatures of brain and cognitive reserve in the rat hippocampus and parahippocampal regions

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-02-07 DOI: 10.1016/j.neurobiolaging.2025.01.010

David J. Horovitz , Laura A. Askins , Grace M. Regnier, Joseph A. McQuail

Age-related cognitive decline varies widely among individuals, with some showing resilience despite older age. This study examines synaptic markers of glutamatergic and GABAergic neurotransmission in the hippocampus and cortex of older rats with differing cognitive abilities, aiming to uncover mechanisms that contribute to cognitive resilience. We observed significant age-related reductions in vesicular glutamate transporter VGluT1, particularly in the stratum oriens (SO), radiatum (SR), and lacunosum-moleculare (SLM) of the dorsal CA3 and SLM of the dorsal CA1. Furthermore, loss of VGluT1 in the dorsal CA3-SLM correlated with severity of memory impairment. Higher levels of the vesicular GABA transporter (VGAT) were associated with better spatial learning in older rats, across several synaptic zones of the dorsal hippocampus, including the outer molecular layer of the dentate gyrus (DG), and the SO, SR, SLM, and pyramidal cell layers of both CA3 and CA1. This suggests that enhanced inhibitory neurotransmission specific to the dorsal aspect of the hippocampus may protect against age-related cognitive decline. While the dorsal hippocampus showed consistent age- and memory-related changes, markers in the ventral hippocampus remained largely intact. In the perirhinal cortex, VGluT1 declined with no changes in VGAT, while both markers remained unchanged in other cortical regions, including the lateral entorhinal, retrosplenial, and posterior parietal cortices. These findings highlight region-specific patterns of synaptic aging as potential markers of brain and cognitive reserve.

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