Aging brain最新文献

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Evaluation of candidate RT-qPCR reference genes in the aging African turquoise killifish brain 老化非洲绿松石鳉脑中候选RT-qPCR内参基因的评价
IF 2.7
Aging brain Pub Date : 2025-01-01 Epub Date: 2025-09-09 DOI: 10.1016/j.nbas.2025.100151
Emily Whisenant, Arne C. Lekven
{"title":"Evaluation of candidate RT-qPCR reference genes in the aging African turquoise killifish brain","authors":"Emily Whisenant,&nbsp;Arne C. Lekven","doi":"10.1016/j.nbas.2025.100151","DOIUrl":"10.1016/j.nbas.2025.100151","url":null,"abstract":"<div><div>Reference genes (RGs) are typically used to normalize gene expression from RT-qPCR experiments. However, the expression of commonly used RGs can vary across different physiological conditions, such as aging, and potentially lead to inaccurate interpretations of results. In African turquoise killifish (<em>Nothobranchius furzeri</em>), the stability of reference genes has not been evaluated during aging. Here, we evaluate six candidate reference genes used in other models of aging (<em>actb</em>, <em>cyc1</em>, <em>gapdh</em>, <em>gusb</em>, <em>oaz1a</em>, and <em>tbp</em>) and examine their brain expression stability in adult males and females from young (10 weeks post-hatching) to old (25 weeks post-hatching). To examine RG stability, we used a combination of summary statistics based on analyses of Cq values, normalized fold change of tyrosine hydroxylase (<em>th</em>), and available computational programs. Overall, we found that <em>cyc1</em>, <em>oaz1a</em>, and <em>gusb</em> were the most stable reference genes during aging across both sexes, with specific rankings reflecting sex-dependent differences, while <em>gapdh</em> and <em>actb</em> were the least reliable. Importantly, when <em>th</em> expression was normalized to our selected RGs, we found that only female samples had an age-related decrease in expression, and expression analysis was highly dependent on the choice of reference gene. Taken together, our findings provide the first systematic evaluation of RG stability in the killifish brain and highlight <em>cyc1</em>, <em>oaz1a</em>, and <em>gusb</em> as reliable RGs for studies of aging. We recommend that future studies use at least two of these RGs in combination for accurate normalization and evaluate RGs for selected experimental conditions within the framework established in this study.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"8 ","pages":"Article 100151"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Complex span measures of working memory do not mediate the effects of age on the P3 and N400 ERPs 工作记忆的复杂广度测量不介导年龄对P3和N400 erp的影响
IF 1.7
Aging brain Pub Date : 2025-01-01 Epub Date: 2025-05-09 DOI: 10.1016/j.nbas.2025.100140
Jasmin Joshi, Chandlyr M. Denaro, Alan A. Hartley, Catherine L. Reed
{"title":"Complex span measures of working memory do not mediate the effects of age on the P3 and N400 ERPs","authors":"Jasmin Joshi,&nbsp;Chandlyr M. Denaro,&nbsp;Alan A. Hartley,&nbsp;Catherine L. Reed","doi":"10.1016/j.nbas.2025.100140","DOIUrl":"10.1016/j.nbas.2025.100140","url":null,"abstract":"<div><div>Working memory (WM), the temporary maintenance of a limited amount of information in an accessible state, is required for the performance of many tasks. Studies have shown that WM demands are related to the neural processing of tasks requiring attention: Age affects the ERP components associated with WM context updating processes in the visual oddball task (P3) and semantic processing in the word-pair judgment task (N400). This study investigated whether WM capacity measured by complex span tasks mediates the effects of age on these ERPs. Younger adults (YA, n = 44, ages 18–23 yr) and older adults (OA, n = 41, ages 69–89 yr) completed operation, reading, and symmetry complex span tasks and two ERP tasks (P3/visual oddball; N400/word-pair judgment). Results showed age-related differences for all complex span tests. Principal components analysis of these tests showed a single factor for both groups, so a combined WM capacity factor score was created. Regressions of age group and WM factor score on P3 and N400 amplitudes and latencies showed that OAs had relatively lower amplitudes and longer latencies. However complex span was not related to P3 or N400 amplitudes or latencies and that result was the same for younger and older adults; that is, complex span did not mediate the age effects. WM processes indexed by the P3 and N400 components appear to be different from those elicited by complex span tasks. Attentional control processes of WM influence oddball and semantic judgement tasks more than storage components.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"7 ","pages":"Article 100140"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Influence of aging and task-related activation on descending cortical modulation of spinal sensorimotor circuitry 衰老和任务相关激活对脊髓感觉运动回路下行皮质调节的影响
IF 2.7
Aging brain Pub Date : 2025-01-01 Epub Date: 2025-10-28 DOI: 10.1016/j.nbas.2025.100153
Alejandro J. Lopez , Terrence J. Glover , Taylor M. Leone , Catherine F. Mason , Camille Guzman , Lena H. Ting , Michael R. Borich , Trisha M. Kesar
{"title":"Influence of aging and task-related activation on descending cortical modulation of spinal sensorimotor circuitry","authors":"Alejandro J. Lopez ,&nbsp;Terrence J. Glover ,&nbsp;Taylor M. Leone ,&nbsp;Catherine F. Mason ,&nbsp;Camille Guzman ,&nbsp;Lena H. Ting ,&nbsp;Michael R. Borich ,&nbsp;Trisha M. Kesar","doi":"10.1016/j.nbas.2025.100153","DOIUrl":"10.1016/j.nbas.2025.100153","url":null,"abstract":"<div><div>The objective of this study was to evaluate the effects of aging on descending modulation of spinal reflexes across different task conditions. In healthy young (YA; age 27 ± 4 years) and older (OA; age 63 ± 10 years) adults, we utilized paired subthreshold transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) to elicit unconditioned (PNS only) and conditioned (TMS paired with PNS) soleus Hoffmann (H-)reflexes at 3 inter-stimulus intervals (ISIs) (−1.5, +10 ms, +40 ms) and during 3 task conditions − sit rest (SR), sit active (SA), and quiet stance (QS). Our results showed that at the + 40 ms ISI, compared to YA, the OA group showed significant differences in modulation (and reversal from facilitation to inhibition) of soleus H-reflexes during both SA and QS tasks (p &lt; 0.0001). Correlation analysis showed a significant negative relationship between age and the magnitude of H-reflex modulation at the + 40 ms ISI, such that older individuals showed a larger magnitude of H-reflex inhibition. In conclusion, altered task-related modulation of spinal reflexes at the + 40 ms ISI may reflect specific aging-related effects on spinal sensorimotor integration, likely mediated via complex interactions between the influence of polysynaptic slower-conducting descending pathways, sensory afferents, and local spinal circuits, on spinal reflex activity during motor task performance.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"8 ","pages":"Article 100153"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145416164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of novel candidate loci for Alzheimer’s disease and related dementias by leveraging the shared genetic basis with hippocampal volume 利用与海马体积共享的遗传基础,鉴定阿尔茨海默病和相关痴呆的新候选基因座
IF 2.7
Aging brain Pub Date : 2025-01-01 Epub Date: 2025-07-30 DOI: 10.1016/j.nbas.2025.100147
Chenyang Jiang , Sven J. van der Lee , Niccolò Tesi , Wiesje M. van der Flier , Betty M. Tijms , Lianne M. Reus
{"title":"Identification of novel candidate loci for Alzheimer’s disease and related dementias by leveraging the shared genetic basis with hippocampal volume","authors":"Chenyang Jiang ,&nbsp;Sven J. van der Lee ,&nbsp;Niccolò Tesi ,&nbsp;Wiesje M. van der Flier ,&nbsp;Betty M. Tijms ,&nbsp;Lianne M. Reus","doi":"10.1016/j.nbas.2025.100147","DOIUrl":"10.1016/j.nbas.2025.100147","url":null,"abstract":"<div><div>Alzheimer’s disease and related dementias (ADRD) are complex neurodegenerative disorders of which the genetic basis remains incompletely understood. Hippocampal volume loss is a core hallmark of AD. Hippocampal volume also has a strong heritable component and its genetic underpinnings may help us to understand the complex biological mechanism underlying ADRD. To identify shared genetic risk loci across late-onset ADRD and bilateral hippocampal volumes, we conducted a cross-trait analysis of existing GWAS data on the two traits using the conjunctional false discovery rate (conjFDR) framework. Functional annotation and phenome-wide association studies (PheWAS) were performed on the identified shared loci to characterize their biological relevance. We identified 11 unique lead genetic loci, of which 7 loci showed discordant directional effects (loci associated with increased risk for ADRD and smaller hippocampal volumes). We found that <em>SHARPIN</em> and <em>TNIP1</em> genes play a role in ADRD by affecting hippocampal volumes. In addition, we observed 9 novel ADRD-hippocampus loci in genes previously implicated in AD (<em>IGIP</em> and <em>ACE</em>) and novel ADRD-genes (<em>KCTD13</em>, <em>HINT1</em>, <em>SH3TC2</em>, <em>FAM53B</em>, <em>TPM1</em>, <em>IL34</em> and <em>SSH2</em>). PheWAS results show that most shared loci associated with neuroimaging measurements, white blood cell markers, red blood cell markers, and lipids. This study shows a shared genetic basis between ADRD and bilateral hippocampal volumes. By integrating summary statistics for these two traits, we identified both novel and previously reported ADRD-hippocampus loci. Functional analysis highlights the role of immune cells and lipid markers in the shared loci, suggesting a shared neurobiological basis for ADRD and bilateral hippocampal volumes.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"8 ","pages":"Article 100147"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cellular senescence, neuroinflammation, and microRNAs: Possible interactions driving aging and neurodegeneration in the hippocampal neurogenic niche 细胞衰老、神经炎症和microrna:海马神经源性生态位中驱动衰老和神经变性的可能相互作用
IF 1.7
Aging brain Pub Date : 2025-01-01 Epub Date: 2025-06-12 DOI: 10.1016/j.nbas.2025.100141
O. Polzer , E. Kinloch , C.P. Fitzsimons
{"title":"Cellular senescence, neuroinflammation, and microRNAs: Possible interactions driving aging and neurodegeneration in the hippocampal neurogenic niche","authors":"O. Polzer ,&nbsp;E. Kinloch ,&nbsp;C.P. Fitzsimons","doi":"10.1016/j.nbas.2025.100141","DOIUrl":"10.1016/j.nbas.2025.100141","url":null,"abstract":"<div><div>Cellular senescence influences normal physiology and ageing-related diseases, including neurodegeneration. Senescent cells accumulate with age in the brain, secreting pro-inflammatory factors that promote neuroinflammation, which has been linked to disorders like Alzheimer’s and Parkinson’s. Neurons and other brain cells such as microglia, astrocytes, and neural stem/progenitor cells (NSPCs), exhibit senescence in aged brains. NSPCs, essential for neurogenesis, may enter senescence due to inflammatory signals and other factors and microRNAs may regulate this process. Here we discuss senescence mechanisms, neuroinflammation, and potential therapeutic targets, proposing that modulating senescence by microRNA-mediated pathways could help combat neurodegenerative diseases.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"8 ","pages":"Article 100141"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144262539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Selenium deficiency negatively affects survival and integrity of human hippocampal progenitor cells 缺硒对人海马祖细胞的存活和完整性有负面影响
IF 1.7
Aging brain Pub Date : 2025-01-01 Epub Date: 2025-04-30 DOI: 10.1016/j.nbas.2025.100138
Sahand Farmand, Emaan Ahmed, Hadisa Azizi Zawar, Sandrine Thuret
{"title":"Selenium deficiency negatively affects survival and integrity of human hippocampal progenitor cells","authors":"Sahand Farmand,&nbsp;Emaan Ahmed,&nbsp;Hadisa Azizi Zawar,&nbsp;Sandrine Thuret","doi":"10.1016/j.nbas.2025.100138","DOIUrl":"10.1016/j.nbas.2025.100138","url":null,"abstract":"<div><div>Selenium has been shown to be a key regulatory element in the health, survival and proliferation of neural stem and progenitor cells, with various studies underlining its anti-aging properties. However, most of this knowledge is derived from rodent models, leaving its effects on human hippocampal progenitor cells unclear. In this study, we utilized a human hippocampal progenitor cell (HPC) line to examine the effects of varying concentrations of sodium selenite, an inorganic form of selenium (0 µM, 0.1 µM, 0.23 µM, 0.5 µM, and 1.0 µM), on the proliferation, apoptosis, and progenitor integrity of these cells. To do this, HPCs were exposed to these concentrations for 48 h, followed by immunocytochemistry to quantify, cell number (DAPI-positive cells), proliferation (KI67-positve cells), apoptosis (CC3-positve cells), and progenitor integrity (SOX2- and Nestin-positive cells). While our results indicated no significant effects of selenium concentrations on proliferation or apoptosis, we demonstrated that absence of selenium (0 μM) in the culture media significantly reduced both cell number and percentage of Nestin-positive cells, but only when compared to the condition with the highest selenium concentration (1.0 μM). Our findings underscore the role of selenium in regulating the survival and integrity of human HPCs. Lastly, we emphasize the need for further research to uncover the mechanisms underlying these observed changes.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"7 ","pages":"Article 100138"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The association of late-life depressive symptoms with brain amyloid-β deposition: the ARIC-PET study 老年抑郁症状与脑淀粉样蛋白-β沉积的关系:ARIC-PET研究
IF 2.7
Aging brain Pub Date : 2025-01-01 Epub Date: 2025-10-30 DOI: 10.1016/j.nbas.2025.100152
Sylee Kanetkar , Valerie N. Morrill , Marco T. Egle , Keenan A. Walker , Dean F. Wong , Rebecca F. Gottesman
{"title":"The association of late-life depressive symptoms with brain amyloid-β deposition: the ARIC-PET study","authors":"Sylee Kanetkar ,&nbsp;Valerie N. Morrill ,&nbsp;Marco T. Egle ,&nbsp;Keenan A. Walker ,&nbsp;Dean F. Wong ,&nbsp;Rebecca F. Gottesman","doi":"10.1016/j.nbas.2025.100152","DOIUrl":"10.1016/j.nbas.2025.100152","url":null,"abstract":"<div><div>Late-life depression is associated with an increased risk of developing dementia related to Alzheimer’s disease, yet the mechanism underlying this relationship remains poorly understood. This study investigated the association of late-life depressive symptoms (LLDS) with brain amyloid deposition by PET. 334 dementia-free individuals from the Atherosclerosis Risk in Communities Study had Florbetapir-PET scans in late-life (ages 67–89). Elevated global and regional brain amyloid deposition was defined as a Florbetapir standardized uptake value ratio (SUVR) &gt; 1.2. <em>LLDS</em> was assessed using the 11-item Center for Epidemiological Studies Depression Scale (CES-D) and defined as late-life CES-D ≥ 9. Several secondary depression measures (e.g., antidepressant use) were also explored. Stratified analyses across race, sex, and cognitive status groups were conducted. Participants (median age 76 years; 57.2 % female; 42.5 % Black; 26.9 % mild cognitive impairment) showed no association of LLDS with global amyloid deposition. Although antidepressant use was not associated with global amyloid overall, antidepressant use was associated with elevated global amyloid in individuals with normal cognition but not mild cognitive impairment. There was no effect modification by race and sex. Overall, our findings suggest that LLDS are generally not associated with global amyloid deposition, but further investigation of this relationship in larger sample sizes is warranted.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"8 ","pages":"Article 100152"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145416163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nigrostriatal dopaminergic neurotransmission and resilience to peripheral systemic risk factors for gait slowing upon transition to uneven surfaces in older adult 黑质纹状体多巴胺能神经传递和对周围系统危险因素的恢复能力在老年人过渡到不平整的表面时步态减慢
IF 1.7
Aging brain Pub Date : 2025-01-01 Epub Date: 2025-06-20 DOI: 10.1016/j.nbas.2025.100143
Lana M. Chahine , Andrea Rosso , Ian Troidl , Mary Ganguli , Anne Newman , Steven Cummings , Stephanie Studenski , Brian Lopresti , Sarah Royse , Theodore Huppert , Mark Redfern , Patrick J. Sparto , Nico I. Bohnen , Caterina Rosano
{"title":"Nigrostriatal dopaminergic neurotransmission and resilience to peripheral systemic risk factors for gait slowing upon transition to uneven surfaces in older adult","authors":"Lana M. Chahine ,&nbsp;Andrea Rosso ,&nbsp;Ian Troidl ,&nbsp;Mary Ganguli ,&nbsp;Anne Newman ,&nbsp;Steven Cummings ,&nbsp;Stephanie Studenski ,&nbsp;Brian Lopresti ,&nbsp;Sarah Royse ,&nbsp;Theodore Huppert ,&nbsp;Mark Redfern ,&nbsp;Patrick J. Sparto ,&nbsp;Nico I. Bohnen ,&nbsp;Caterina Rosano","doi":"10.1016/j.nbas.2025.100143","DOIUrl":"10.1016/j.nbas.2025.100143","url":null,"abstract":"<div><div>Identifying mechanisms that compensate for slow gait speed in older adults is crucial. Dopaminergic neurotransmission curbs deleterious associations of cerebrovascular disease with gait, but whether it compensates for peripheral systemic risk factors (PSRF) for gait slowing has not been studied. In this cross-sectional study of community-dwelling older adults, we examined the relationship between nigrostriatal dopaminergic terminal integrity and gait speed in individuals with and without ≥ 1 PSRF for gait slowing: obesity, joint pain, or reduced muscle strength. The primary outcome was gait speed cost (%GSC) on transition from even to uneven surface. Participants underwent dopaminergic imaging with dihydrotetrabenazine [<sup>11</sup>C]DTBZ positron emission tomography. Among 197 individuals, (mean (SD) age 74.92 (4.53) years; 61.93 % female; 90.86 % White), 130 (65.99 %) had ≥ 1 PSRF. Relationship between posterior putamen [<sup>11</sup>C]DTBZ binding and %GSC was modified by PSRF; in those with ≥ 1 PSRF (but not in those with no PSRF), posterior putamen [<sup>11</sup>C]DTBZ binding was associated with %GSC (β = 0.198, p = 0.03) independent of potential confounders. This cross-sectional study indicates that higher striatal dopaminergic neurotransmission may compensate for the effects of PSRF on gait slowing.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"8 ","pages":"Article 100143"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of global Ripk2 genetic deficiency in aged mice following experimental ischemic stroke Ripk2基因缺失对实验性缺血性脑卒中老年小鼠的影响
IF 1.7
Aging brain Pub Date : 2025-01-01 Epub Date: 2025-03-29 DOI: 10.1016/j.nbas.2025.100135
John Aaron Howell , Jonathan Larochelle , Rachel E. Gunraj , Sofia M. Stansbury , Lei Liu , Changjun Yang , Eduardo Candelario-Jalil
{"title":"Effects of global Ripk2 genetic deficiency in aged mice following experimental ischemic stroke","authors":"John Aaron Howell ,&nbsp;Jonathan Larochelle ,&nbsp;Rachel E. Gunraj ,&nbsp;Sofia M. Stansbury ,&nbsp;Lei Liu ,&nbsp;Changjun Yang ,&nbsp;Eduardo Candelario-Jalil","doi":"10.1016/j.nbas.2025.100135","DOIUrl":"10.1016/j.nbas.2025.100135","url":null,"abstract":"<div><div>Besides the loss of blood and oxygen reaching the ischemic tissue, many secondary effects of ischemic stroke can cause additional tissue damage, including inflammation, oxidative stress, and proteomic disturbances. Receptor-interacting serine/threonine kinase 2 (RIPK2) is an important mediator in the post-stroke inflammatory cascade that responds to signals and molecular patterns released by dead or dying cells in the ischemic area. We hypothesize that RIPK2 signaling worsens injury and neurological recovery post-stroke and that global deletion of <em>Ripk2</em> is protective following ischemic stroke in aged mice. Aged (18–24 months) male mice were subjected to permanent middle cerebral artery occlusion (pMCAO). Vertical grid, weight grip, and open field were conducted at baseline and on days 1, 2, 3, 8, 15, and 22 post-stroke. Cognitive tests (novel object recognition and Y-maze) were performed at baseline and day 28 post-stroke. Infarct size was measured using cresyl violet staining, and reactive gliosis was measured using Iba1 and GFAP staining at day 28 post-stroke. Global deletion of <em>Ripk2</em> (<em>Ripk2<sup>-/-</sup></em>) in aged mice resulted in smaller infarct volume and improved performance on vertical grid and weight grip tests compared to aged wildtype (WT) mice. Additionally, aged <em>Ripk2</em><sup>-/-</sup> mice had less Iba1 staining in the ipsilateral cortex than the aged WT control mice. This study further elucidates the role of RIPK2 signaling in the ischemic cascade and expands our knowledge of RIPK2 in stroke to aged mice. These results support the hypothesis that RIPK2 signaling worsens injury post-stroke and may be an attractive candidate for therapeutic intervention.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"7 ","pages":"Article 100135"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
White matter differences between younger and older adults revealed by fixel-based analysis 基于固定颗粒的分析揭示了年轻人和老年人的白质差异
IF 1.7
Aging brain Pub Date : 2024-01-01 Epub Date: 2024-11-23 DOI: 10.1016/j.nbas.2024.100132
Feliberto de la Cruz , Andy Schumann , Katrin Rieger , Daniel Güllmar , Jürgen R. Reichenbach , Karl-Jürgen Bär
{"title":"White matter differences between younger and older adults revealed by fixel-based analysis","authors":"Feliberto de la Cruz ,&nbsp;Andy Schumann ,&nbsp;Katrin Rieger ,&nbsp;Daniel Güllmar ,&nbsp;Jürgen R. Reichenbach ,&nbsp;Karl-Jürgen Bär","doi":"10.1016/j.nbas.2024.100132","DOIUrl":"10.1016/j.nbas.2024.100132","url":null,"abstract":"<div><div>The process of healthy aging involves complex alterations in neural structures, with white matter (WM) changes significantly impacting cognitive and motor functions. Conventional methods such as diffusion tensor imaging provide valuable insights, but their limitations in capturing complex WM geometry advocate for more advanced approaches. In this study involving 120 healthy volunteers, we investigated whole-brain WM differences between young and old individuals using a novel technique called fixel-based analysis (FBA). This approach revealed that older adults exhibited reduced FBA-derived metrics in several WM tracts, with frontal areas particularly affected. Surprisingly, age-related differences in FBA-derived measures showed no significant correlation with risk factors such as alcohol consumption, exercise frequency, or pulse pressure but predicted cognitive performance. These findings emphasize FBA’s potential in characterizing complex WM changes and the link between cognitive abilities and WM alterations in healthy aging. Overall, this study advances our understanding of age-related neurodegeneration, highlighting the importance of comprehensive assessments that integrate advanced neuroimaging techniques, cognitive evaluation, and demographic factors to gain insights into healthy aging.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"6 ","pages":"Article 100132"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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