Neurobiology of Aging最新文献

{"title":"Targeting neuronal activity and neuroinflammation for the treatment of Alzheimer’s disease in a mouse model","authors":"Chongzhen Yuan ,&nbsp;Long Li ,&nbsp;Hsiao-yun Lin ,&nbsp;Antonio v. Aubry ,&nbsp;Lyonna F. Parise ,&nbsp;Carole Morel ,&nbsp;Fiona Chen ,&nbsp;Jean Wong ,&nbsp;Scott J. Russo ,&nbsp;Jun Wang","doi":"10.1016/j.neurobiolaging.2025.10.006","DOIUrl":"10.1016/j.neurobiolaging.2025.10.006","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is characterized by progressive cognitive decline driven by complex pathological processes, including tau hyperphosphorylation (p-Tau), amyloid-beta (Aβ) accumulation, and neuroinflammation. In this study, we investigated the effects of two bioactive compounds, dihydrocaffeic acid (DHCA) and malvidin-glucoside (Mal-gluc), targeting inflammation and neuronal activity, respectively, on cognitive function and AD pathology in a mouse model of AD. Our results demonstrate that chronic DHCA/Mal-gluc treatment significantly improves recognition memory in 3xTg-AD mice without reducing p-Tau or Aβ burden. Employing a newly developed whole-brain cFOS and IBA-1 mapping technique, we found that this combination treatment enhances neuronal activity and promotes microglial homeostasis across multiple brain regions in 3xTg-AD mice. These findings underscore the potential of restoring neuronal function and immune homeostasis as a therapeutic approach for AD. Future study will explore the underlying mechanisms and evaluate whether DHCA/Mal-gluc, combined with currently approved Aβ monoclonal therapy, can synergistically prevent or delay AD onset and progression.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"157 ","pages":"Pages 111-118"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467021","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}

{"title":"EEG slow waves and cognitive decline in Isolated Rapid Eye Movements Behavior Disorder: A multicenter longitudinal study","authors":"Caterina Leitner ,&nbsp;Dario Arnaldi ,&nbsp;Francesca Casoni ,&nbsp;Michela Figorilli ,&nbsp;Beatrice Orso ,&nbsp;Pietro Mattioli ,&nbsp;Valter Rustioni ,&nbsp;Monica Puligheddu ,&nbsp;Luigi De Gennaro ,&nbsp;Michele Terzaghi ,&nbsp;Luigi Ferini-Strambi ,&nbsp;Andrea Galbiati","doi":"10.1016/j.neurobiolaging.2025.11.001","DOIUrl":"10.1016/j.neurobiolaging.2025.11.001","url":null,"abstract":"<div><div>This multicenter retrospective longitudinal study aims to evaluate the association between electroencephalographic slow oscillations (0.3–1 Hz) and slow waves (1–4 Hz) with cognitive performance, and their impact on phenoconversion in patients affected by isolated rapid eye movement (REM) sleep behavior disorder (iRBD). 69 iRBD patients underwent baseline overnight video-polysomnography, clinical assessment, and a neuropsychological evaluation. Phenoconversion was assessed with a follow-up clinical evaluation. Automatic detection of slow oscillations and slow waves was performed during non-REM sleep stage 2 (N2) and 3 (N3) on frontal and central derivations. Clinical, neuropsychological and electrophysiological measures were compared between converters and non-converters. Correlations were computed between cognitive performance and slow oscillations and slow wave densities, as well as between N2 slow oscillation density and N3 slow/fast wave densities. Time-to-event analyses, including Kaplan-Meier and Cox proportional hazards model were performed to assess phenoconversion risk and potential predictors. 30.36 % of patients phenoconverted to an overt alpha-synucleinopathy with a mean follow-up of 45.57 ± 37.26 months. Both slow wave and slow oscillation densities were significantly associated with cognitive performance. Moreover, slow oscillation density in N2 positively correlated with slow oscillation and slow wave density in N3. At baseline, patients who phenoconverted at follow-up showed significantly lower executive function performance and reduced N2 slow oscillation density. In the Cox model including covariates, only executive functions remained a significant predictor. Baseline differences in executive functions may help identify iRBD patients at greater risk of phenoconversion, whereas reduced N2 slow oscillation density may reflect early neurophysiological alterations preceding overt disease.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"157 ","pages":"Pages 119-126"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467022","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}

{"title":"Verbal learning in logopenic variant Primary Progressive Aphasia: An EEG investigation","authors":"Kyriaki Neophytou ,&nbsp;Panteleimon Chriskos ,&nbsp;Jessica Gallegos ,&nbsp;Alexandros Afthinos ,&nbsp;Constantine E. Frangakis ,&nbsp;Nathan E. Crone ,&nbsp;Panagiotis D. Bamidis ,&nbsp;Argye E. Hillis ,&nbsp;Kyrana Tsapkini","doi":"10.1016/j.neurobiolaging.2025.10.002","DOIUrl":"10.1016/j.neurobiolaging.2025.10.002","url":null,"abstract":"<div><div>The logopenic variant of PPA (lvPPA) is characterized by impaired single-word retrieval and impaired repetition, which suggests a phonological working memory impairment. Phonological working memory is an essential mechanism for verbal learning; thus, one would expect that the verbal learning skills of this population would be thoroughly investigated. Nonetheless, the relevant research is scarce. As a preliminary investigation aiming to deepen our understanding of verbal learning in lvPPA, we studied how resting-state electroencephalographic (EEG) activity relates to the verbal learning abilities in this group. Specifically, short low-density (i.e., 8 channels, bilaterally) EEG recordings were collected from nine lvPPA individuals at resting-state. Activity at the five frequency bands (delta, theta, alpha, beta, gamma) was extracted and correlated with <em>Sum of Trials</em> performance on the Rey Auditory Verbal Learning Test (RAVLT). Our results showed a statistically significant association between delta band activity and verbal learning across the brain, particularly in the left parietal region. Specifically, higher delta power (on average across channels, as well as at each of the eight channels separately) was associated with lower RAVLT scores. EEG activity at the other frequency bands did not show a statistically significant association with verbal learning. These findings provide the first insights into the association of resting-state electrophysiological activity with verbal learning in lvPPA. The findings of this preliminary investigation can be used as guiding evidence in future neuromodulation studies to target activity at specific frequency bands for electrical stimulation both in lvPPA, as well as in other populations with similar learning impairments.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"157 ","pages":"Pages 60-67"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293142","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}

{"title":"Zinc transporter proteins in the retina as potential biomarkers for staging early Alzheimer’s disease: Comparative analysis in human and mouse models","authors":"Seyed Mostafa Hosseinpour Mashkani ,&nbsp;David Bishop ,&nbsp;Paul A. Adlard ,&nbsp;S. Mojtaba Golzan","doi":"10.1016/j.neurobiolaging.2025.09.010","DOIUrl":"10.1016/j.neurobiolaging.2025.09.010","url":null,"abstract":"<div><div>Zinc plays a critical role in memory, learning, and neuronal function, with dysregulation increasingly implicated in neurodegenerative diseases such as Alzheimer’s disease (AD). This study aimed to investigate whether changes in the expression of zinc transporter proteins, ZnT3 and ZIP3, in the retina mirror those in the brain, and to explore their potential as non-invasive biomarkers for early AD detection. Immunofluorescence and Western blotting were used to assess ZnT3 and ZIP3 expression in the retina and hippocampus of APP/PS1 and WT mice (9 and 18 months), as well as in human post-mortem tissues (9 AD and 6 control cases). To further investigate the regulatory role of ZnT3 in zinc homeostasis and its influence on tissue zinc concentrations, we quantified zinc levels in retinal and hippocampal tissues from WT and ZnT3 knockout mice using inductively coupled plasma-mass spectrometry (ICP-MS). ZnT3 and ZIP3 levels were significantly higher in the retina and hippocampus of healthy controls compared to AD cases across both mouse and human samples. ICP-MS analysis confirmed significantly lower zinc concentrations in ZnT3 knockout mice compared to WT controls in both the These findings demonstrate that retinal ZnT3 and ZIP3 expression changes mirror those observed in the hippocampus during AD progression. This suggests their potential as retinal biomarkers for Alzheimer's disease. Notably, ZnT3 shows strong promise for early, non-invasive detection of AD. Further validation in larger cohorts is warranted.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"157 ","pages":"Pages 26-35"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222924","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}

{"title":"Editorial Advisory Board","authors":"","doi":"10.1016/S0197-4580(25)00194-0","DOIUrl":"10.1016/S0197-4580(25)00194-0","url":null,"abstract":"","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"157 ","pages":"Page IFC"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568817","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}

{"title":"Apraxic deficits in Alzheimer’s disease are associated with altered dynamic connectivity in praxis-related networks","authors":"Taylan D. Kuzu ,&nbsp;Elena Brinkmann ,&nbsp;Anna K. Bonkhoff ,&nbsp;Veronika Wunderle ,&nbsp;Gérard N. Bischof ,&nbsp;Kathrin Giehl ,&nbsp;Maximilian H.T. Schmieschek ,&nbsp;Oezguer A. Onur ,&nbsp;Frank Jessen ,&nbsp;Gereon R. Fink ,&nbsp;Alexander Drzezga ,&nbsp;Peter H. Weiss","doi":"10.1016/j.neurobiolaging.2025.09.007","DOIUrl":"10.1016/j.neurobiolaging.2025.09.007","url":null,"abstract":"<div><div>Apraxia is a common symptom in Alzheimer’s disease (AD) that reduces autonomy and quality of life. However, the neural basis underlying apraxia in AD, for example, reflected by functional connectivity (FC) alterations, remains unexplored. We investigated static and dynamic FC using resting-state functional imaging in 14 patients with biomarker-confirmed AD pathology and 14 matched healthy participants. FC was estimated as average (static) and short-term (dynamic) connectivity strengths between motor- and praxis-related functional networks. Recurring connectivity patterns were clustered into dynamic states to compute temporal connectivity measures. Connectivity measures were used for correlations with apraxic deficits. In AD patients, static connectivity between visual and inferior parietal networks correlated with apraxic imitation (<em>r</em> = 0.762, <em>P</em>_<em>FDR</em> = 0.043) and arm/hand gesture deficits (<em>r</em> = 0.848, <em>P</em>_<em>FDR</em> = 0.020), while dynamic connectivity between these networks correlated with apraxic imitation deficits (<em>r</em> = 0.851, <em>P</em>_<em>FDR</em> = 0.020). Dynamic FC analysis revealed a segregated and integrated state. AD patients spent more time overall (fraction time, <em>P</em>_<em>FDR</em> &lt; 0.001) and remained longer without switching (dwell time, <em>P</em>_<em>FDR</em> = 0.004) in the segregated state. Both fraction (<em>ρ</em> = –0.858, <em>P</em>_<em>FDR</em> = 0.015) and dwell time (<em>ρ</em> = –0.914, <em>P</em>_<em>FDR</em> = 0.003) correlated with apraxic imitation deficits. Connectivity strengths between visual and inferior parietal networks and fraction time in the segregated state predicted apraxic imitation deficits (adjusted <em>R</em>^<em>2</em> = 0.782, <em>P</em> &lt; 0.001). We conclude that apraxia in AD patients is associated with altered FC in praxis-related networks, suggesting FC as a potential clinical indicator for predicting motor-cognitive deficits.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"157 ","pages":"Pages 36-47"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252256","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}

{"title":"Proteomic polygenic risk scores of age-related plasma protein levels reveal a role for Metalloproteinase inhibitor 2 (TIMP2) in cognitive performance","authors":"Federica Anastasi ,&nbsp;Patricia Genius ,&nbsp;Blanca Rodriguez-Fernandez ,&nbsp;Chengran Yang ,&nbsp;Priyanka Gorijala ,&nbsp;Jigyasha Timsina ,&nbsp;Felipe Hernández-Villamizar ,&nbsp;Luigi Lorenzini ,&nbsp;Marta del Campo ,&nbsp;Gonzalo Sánchez-Benavides ,&nbsp;Carolina Minguillon ,&nbsp;Arcadi Navarro ,&nbsp;Carlos Cruchaga ,&nbsp;Marc Suárez-Calvet ,&nbsp;Natalia Vilor-Tejedor","doi":"10.1016/j.neurobiolaging.2025.10.003","DOIUrl":"10.1016/j.neurobiolaging.2025.10.003","url":null,"abstract":"<div><div>Several studies in mice have identified blood proteins that influence brain aging, yet translating these findings into humans remains challenging. To address this gap, we conducted a systematic review that identified 12 proteins reported to have an aging or rejuvenating effect in murine brains. Using protein quantitative trait loci data, we computed proteomic polygenic risk scores (protPRSs) capturing the lifelong genetic predisposition to higher or lower plasma protein levels and their regulation. We first validated the prediction accuracy of these protPRSs in two independent cohorts: 10 protPRSs in the Knight-ADRC and 7 protPRSs in the ALFA+ cohort significantly predicted their corresponding protein levels, although effect sizes were modest. We then examined their association with cognitive performance in cognitively unimpaired individuals at risk of Alzheimer’s disease of the ALFA+ cohort. Among the protPRSs tested, the metalloproteinase inhibitor 2 (TIMP2) protPRS was significantly associated with better global cognition and episodic memory. These associations were consistent across stratifications by sex, <em>APOE</em>-ε4, and amyloid-β status, although some did not survive multiple testing corrections. TIMP2 protPRS correlated with measured TIMP2 levels, but actual plasma concentrations were not significantly related to cognition. This finding aligns with murine evidence of TIMP2's brain-rejuvenating role. By leveraging genetic predisposition to protein abundance and regulation, protPRSs may provide complementary insight into long-term biological processes not captured by single protein measurements. Our results support TIMP2 as a candidate for further investigation in the context of brain aging and cognitive decline.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"157 ","pages":"Pages 68-78"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145409655","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}

{"title":"Identification of circular RNAs associated with ageing of the dorsolateral prefrontal cortex across the adult lifespan","authors":"Fatemeh Amjadi-Moheb ,&nbsp;Sumangali Gobhidharan ,&nbsp;Adith Mohan ,&nbsp;Perminder S. Sachdev ,&nbsp;Anbupalam Thalamuthu ,&nbsp;Karen A. Mather","doi":"10.1016/j.neurobiolaging.2025.10.001","DOIUrl":"10.1016/j.neurobiolaging.2025.10.001","url":null,"abstract":"<div><div>Circular RNAs (circRNAs) are emerging as crucial regulators of biological processes and have been implicated in age-related diseases. Few studies have explored age-related circRNA expression in the human brain across the adult lifespan. This study aims to identify age-related differentially expressed circRNAs in human post-mortem dorsolateral prefrontal cortex (DLPFC) samples, a region critically involved in cognition that exhibits early signs of age-related changes. Total RNA sequencing was conducted on a discovery cohort of 67 post-mortem DLPFC samples, from individuals with no neurological disease diagnosis at the time of death (35–103 years). CircRNAs were identified using CIRCexplorer2, with 11,907 circRNAs available for analyses. Linear regression was used to analyse the relationships between circRNA expression and age at death. Replication of the results was performed in an independent neurologically healthy dataset from the CommonMind Consortium (n = 321, age at death: 35–91 years). Co-expression network analysis was performed to identify modules of highly co-expressed circRNAs associated with age. Potential microRNA and RNA-binding protein target sites were predicted. In the discovery dataset, 37 circRNAs were age-associated (FDR &lt;0.05). Seven out of the 37 were successfully replicated. The host genes of replicated age-associated circRNAs are implicated in synapse regulation. Co-expression analysis revealed two circRNA modules significantly correlated with age. We identified 484 microRNA and 99 RNA-binding protein target sites on the replicated circRNAs. In conclusion, seven age-associated circRNAs were identified as important candidates for involvement in post-transcriptional regulatory networks in the DLPFC. Future studies should aim to elucidate their functional roles in brain ageing.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"157 ","pages":"Pages 48-59"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145269708","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}

{"title":"Microstructural changes in locus coeruleus-cortical projections in aged bonnet macaques are independent of myelin loss","authors":"Kelsey E. McDermott ,&nbsp;Laurel Dieckhaus ,&nbsp;Courtney Comrie ,&nbsp;Victor Sandrin ,&nbsp;Elizabeth B. Hutchinson ,&nbsp;Carol A. Barnes","doi":"10.1016/j.neurobiolaging.2025.09.009","DOIUrl":"10.1016/j.neurobiolaging.2025.09.009","url":null,"abstract":"<div><div>The locus coeruleus (LC) is a brainstem nucleus best known for being the primary site of noradrenaline production for the forebrain and is involved in the modulation and optimization of behavioral performance. The LC has many targets throughout the cortex, and ascending projections from the LC join the central tegmental tract (CTT), a well-defined white matter brainstem tract in the pons that terminates in the thalamus. Evidence indicates that the LC is one of the first brain regions to show pathological burden in Alzheimer’s disease (AD), and AD patients exhibit structural alterations in the LC and its ascending projections. The extent to which changes occur in the LC and its projections in normal aging, however, is less clear. Analysis of LC-forebrain tractography has historically been difficult due to the small size of the LC as well as the abundance of crossing fibers in the brainstem. <em>Ex vivo</em> magnetic resonance imaging (MRI) allows us to overcome some of these setbacks, as longer scan times can be used to generate higher resolution images than is possible in live subjects. Here, we utilize a cohort of bonnet macaques, an excellent model of normative aging, and analyze the microstructure of the LC and its projections that join the CTT with respect to age. We have been able to overcome issues associated with LC tractography and have found a negative association with age and diffusivity.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"157 ","pages":"Pages 17-25"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207073","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}

{"title":"Age-related ultrastructural differences in the dorsal cortex of the inferior colliculus in the fischer brown Norway rat","authors":"Dakota Z. Smallridge ,&nbsp;Kylee Tenney ,&nbsp;Gillian L. Barach ,&nbsp;Gurveer Singh ,&nbsp;Erin N. Beskitt ,&nbsp;Justine Busby ,&nbsp;Syllissa Duncan ,&nbsp;Alexa Wawrzyniak ,&nbsp;Brenda Vega ,&nbsp;Nick J. Tokar ,&nbsp;Andrew P. Ohl ,&nbsp;Jesse W. Young ,&nbsp;Jeffrey G. Mellott","doi":"10.1016/j.neurobiolaging.2025.09.008","DOIUrl":"10.1016/j.neurobiolaging.2025.09.008","url":null,"abstract":"<div><div>The inferior colliculus (IC) is a nucleus in the auditory midbrain that plays an important role in sound and speech processing through how it encodes temporal precision. Temporal precision depends on the balance of inhibition and excitation within the IC. This balance degrades during aging. Age-related changes in synapses have been described in the lemniscal IC as a contributing factor for this imbalance. However, it is unknown if aging affects synapses throughout the non-lemniscal IC in a similar manner. We sought to determine this by examining the dorsal cortex of the IC (ICd). The ICd is a non-lemniscal nucleus that is well known for its extensive innervation by the auditory cortex. Electron microscopy techniques were used across age groups of younger age (2–3 months), middle age (19–21 months) and older age (27–29 months) Fischer Brown Norway rats. Our data demonstrates a small loss of GABAergic synaptic density in middle age, with a significant (34 %) loss during older age. Unlike previous reports of the aging ultrastructure of the IC, asymmetric synaptic density in the ICd remained unchanged. We also demonstrate decreases with age in terminal area and mitochondrial ultrastructure across both synaptic types. Lastly, far fewer asymmetric inputs were observed onto larger GABAergic dendrites. Collectively our data suggest a net loss of inhibition in the ICd. Thus, the balance of excitation and inhibition in the ICd is likely altered and may contribute to factors underlying age-related hearing loss.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"157 ","pages":"Pages 1-16"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145128264","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}