CCL

Összesen 9 találat.
#/oldal:
Részletezés:
Rendezés:

1.

001-es BibID:BIBFORM101050
Első szerző:Balasubramanian, Priya
Cím:Obesity-induced cognitive impairment in older adults : a microvascular perspective / Balasubramanian Priya, Kiss Tamas, Tarantini Stefano, Nyúl-Tóth Ádám, Ahire Chetan, Yabluchanskiy Andriy, Csipo Tamas, Lipecz Agnes, Tabak Adam, Institoris Adam, Csiszar Anna, Ungvari Zoltan
Dátum:2021
ISSN:0363-6135
Megjegyzések:Over two-thirds of individuals aged 65 and older are obese or overweight in the United States. Epidemiological data show an association between the degree of adiposity and cognitive dysfunction in the elderly. In this review, the pathophysiological roles of microvascular mechanisms, including impaired endothelial function and neurovascular coupling responses, microvascular rarefaction, and blood-brain barrier disruption in the genesis of cognitive impairment in geriatric obesity are considered. The potential contribution of adipose-derived factors and fundamental cellular and molecular mechanisms of senescence to exacerbated obesity-induced cerebromicrovascular impairment and cognitive decline in aging are discussed.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:American Journal Of Physiology-Heart And Circulatory Physiology. - 320 : 2 (2021), p. H740-H761. -
További szerzők:Kiss Tamás (1950-) (vegyész) Tarantini, Stefano Nyúl-Tóth Ádám Ahire, Chetan Yabluchanskiy, Andriy Csípő Tamás (1990-) Lipécz Ágnes Tabák Ádám Institóris Ádám Csiszár Anna Ungvári Zoltán
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

2.

001-es BibID:BIBFORM099947
035-os BibID:(WOS)000493706100001 (Scopus)85074834329
Első szerző:Csípő Tamás
Cím:Assessment of age-related decline of neurovascular coupling responses by functional near-infrared spectroscopy (fNIRS) in humans / Csipo Tamas, Mukli Peter, Lipecz Agnes, Tarantini Stefano, Bahadli Dhay, Abdulhussein Osamah, Owens Cameron, Kiss Tamas, Balasubramanian Priya, Nyúl-Tóth Ádám, Hand Rachel A., Yabluchanska Valeriya, Sorond Farzaneh A., Csiszar Anna, Ungvari Zoltan, Yabluchanskiy Andriy
Dátum:2019
ISSN:2509-2715 2509-2723
Megjegyzések:Preclinical studies provide strong evidence that age-related impairment of neurovascular coupling (NVC) plays a causal role in the pathogenesis of vascular cognitive impairment (VCI). NVC is a critical homeostatic mechanism in the brain, responsible for adjustment of local cerebral blood flow to the energetic needs of the active neuronal tissue. Recent progress in geroscience has led to the identification of critical cellular and molecular mechanisms involved in neurovascular aging, identifying these pathways as targets for intervention. In order to translate the preclinical findings to humans, there is a need to assess NVC in geriatric patients as an endpoint in clinical studies. Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging technique that enables the investigation of local changes in cerebral blood flow, quantifying task-related changes in oxygenated and deoxygenated hemoglobin concentrations. In the present overview, the basic principles of fNIRS are introduced and the application of this technique to assess NVC in older adults with implications for the design of studies on the mechanistic underpinnings of VCI is discussed.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Aging
Cognitive aging
Functional near-infrared spectroscopy
Neurovascular coupling
VCI
VCID
Vascular cognitive impairment and dementia
fNIRS
Megjelenés:GeroScience. - 41 : 5 (2019), p. 495-509. -
További szerzők:Mukli Péter Lipécz Ágnes Tarantini, Stefano Bahadli, Dhay Abdulhussein, Osamah Owens, Cameron D. Kiss Tamás (1950-) (vegyész) Balasubramanian, Priya Nyúl-Tóth Ádám Hand, Rachel A. Yabluchanska, Valeriya Sorond, Farzaneh A. Csiszár Anna Ungvári Zoltán Yabluchanskiy, Andriy
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

3.

001-es BibID:BIBFORM099943
035-os BibID:(WOS)000469877700003 (Scopus)85066471327
Első szerző:Csípő Tamás
Cím:Age-related decline in peripheral vascular health predicts cognitive impairment / Csipo Tamas, Lipecz Agnes, Fulop Gabor A., Hand Rachel A., Ngo Bich-Thy N., Dzialendzik Mikita, Tarantini Stefano, Balasubramanian Priya, Kiss Tamas, Yabluchanska Valeriya, Silva-Palacios Federico, Courtney Donald L., Dasari Tarun W., Sorond Farzaneh, Sonntag William E., Csiszar Anna, Ungvari Zoltan, Yabluchanskiy Andriy
Dátum:2019
ISSN:2509-2715 2509-2723
Megjegyzések:Preclinical studies demonstrate that generalized endothelial cell dysfunction and microvascular impairment are potentially reversible causes of age-related vascular cognitive impairment and dementia (VCID). The present study was designed to test the hypothesis that severity of age-related macro- and microvascular dysfunction measured in the peripheral circulation is an independent predictor of cognitive performance in older adults. In this study, we enrolled 63 healthy individuals into young (< 45 years old) and aged (> 65 years old) groups. We used principal component analysis (PCA) to construct a comprehensive peripheral vascular health index (VHI) encompassing peripheral microvascular reactivity, arterial endothelial function, and vascular stiffness, as a marker of aging-induced generalized vascular dysfunction. Peripheral macrovascular and microvascular endothelial function were assessed using flow-mediated dilation (FMD) and laser speckle contrast imaging tests. Pulse waveform analysis was used to evaluate the augmentation index (AIx), a measure of arterial stiffness. Cognitive function was measured using a panel of CANTAB cognitive tests, and PCA was then applied to generate a cognitive impairment index (CII) for each participant. Aged subjects exhibited significantly impaired macrovascular endothelial function (FMD, 5.6 ? 0.7% vs. 8.3 ? 0.6% in young, p = 0.0061), increased arterial stiffness (AIx 29.3 ? 1.8% vs 4.5 ? 2.6% in young, p < 0.0001), and microvascular dysfunction (2.8 ? 0.2 vs 3.4 ? 0.1-fold change of perfusion in young, p = 0.032). VHI showed a significant negative correlation with age (r = - 0.54, p < 0.0001) and CII significantly correlated with age (r = 0.79, p < 0.0001). VHI significantly correlated with the CII (r = - 0.46, p = 0.0003). A decline in peripheral vascular health may reflect generalized vascular dysfunction and predict cognitive impairment in older adults.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Aging
Endothelial function
Cognitive impairment
Microvascular dysfunction
VCID
Megjelenés:GeroScience. - 41 : 2 (2019), p. 125-136. -
További szerzők:Lipécz Ágnes Fülöp Gábor Áron (1988-) (általános orvos) Hand, Rachel A. Ngo, Bich-Thy N. Dzialendzik, Mikita Tarantini, Stefano Balasubramanian, Priya Kiss Tamás (1950-) (vegyész) Yabluchanska, Valeriya Silva-Palacios, Federico Courtney, Donald L. Dasari, Tarun W. Sorond, Farzaneh A. Sonntag, William E. Csiszár Anna Ungvári Zoltán Yabluchanskiy, Andriy
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

4.

001-es BibID:BIBFORM099929
035-os BibID:(WOS)000531041500024 (Scopus)85082710654
Első szerző:Kiss Tamás (vegyész)
Cím:Circulating anti-geronic factors from heterochonic parabionts promote vascular rejuvenation in aged mice : transcriptional footprint of mitochondrial protection, attenuation of oxidative stress, and rescue of endothelial function by young blood / Kiss Tamas, Tarantini Stefano, Csipo Tamas, Balasubramanian Priya, Nyúl-Tóth Ádám, Yabluchanskiy Andriy, Wren Jonathan D., Garman Lori, Huffman Derek M., Csiszar Anna, Ungvari Zoltan
Dátum:2020
ISSN:2509-2715 2509-2723
Megjegyzések:Aging-induced functional and phenotypic alterations of the vasculature (e.g., endothelial dysfunction, oxidative stress) have a central role in morbidity and mortality of older adults. It has become apparent in recent years that cell autonomous mechanisms alone are inadequate to explain all aspects of vascular aging. The present study was designed to test the hypothesis that age-related changes in circulating anti-geronic factors contribute to the regulation of vascular aging processes in a non-cell autonomous manner. To test this hypothesis, through heterochronic parabiosis we determined the extent, if any, to which endothelial function, vascular production of ROS, and shifts in the vascular transcriptome (RNA-seq) are modulated by the systemic environment. We found that in aortas isolated from isochronic parabiont aged (20-month-old) C57BL/6 mice [A-(A); parabiosis for 8 weeks] acetylcholine-induced endothelium-dependent relaxation was impaired and ROS production (dihydroethidium fluorescence) was increased as compared with those in aortas from young isochronic parabiont (6-month-old) mice [Y-(Y)]. The presence of young blood derived from young parabionts significantly improved endothelium-dependent vasorelaxation and attenuated ROS production in vessels of heterochronic parabiont aged [A-(Y)] mice. In aortas derived from heterochronic parabiont young [Y-(A)] mice, acetylcholine-induced relaxation and ROS production were comparable with those in aortas derived from Y-(Y) mice. Using RNA-seq we assessed transcriptomic changes in the aortic arch associated with aging and heterochronic parabiosis. We identified 347 differentially expressed genes in A-(A) animals compared with Y-(Y) controls. We have identified 212 discordant genes, whose expression levels differed in the aged phenotype, but have shifted back toward the young phenotype by the presence of young blood in aged A-(Y) animals. Pathway analysis shows that vascular protective effects mediated by young blood-regulated genes include mitochondrial rejuvenation. In conclusion, a relatively short-term exposure to young blood can rescue vascular aging phenotypes, including attenuation of oxidative stress, mitochondrial rejuvenation, and improved endothelial function. Our findings provide additional evidence supporting the significant plasticity of vascular aging and evidence for the existence of anti-geronic factors capable of exerting rejuvenating effects on the aging vasculature.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:GeroScience. - 42 : 2 (2020), p. 727-748. -
További szerzők:Tarantini, Stefano Csípő Tamás (1990-) Balasubramanian, Priya Nyúl-Tóth Ádám Yabluchanskiy, Andriy Wren, Jonathan D. Garman, Lori Huffman, Derek M. Csiszár Anna Ungvári Zoltán
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

5.

001-es BibID:BIBFORM099926
035-os BibID:(WOS)000522703800001 (Scopus)85083217977
Első szerző:Kiss Tamás (vegyész)
Cím:Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain / Kiss Tamas, Nyúl-Tóth Ádám, Balasubramanian Priya, Tarantini Stefano, Ahire Chetan, DelFavero Jordan, Yabluchanskiy Andriy, Csipo Tamas, Farkas Eszter, Wiley Graham, Garman Lori, Csiszar Anna, Ungvari Zoltan
Dátum:2020
ISSN:2509-2715 2509-2723
Megjegyzések:Age-related phenotypic changes of cerebromicrovascular endothelial cells lead to dysregulation of cerebral blood flow and blood-brain barrier disruption, promoting the pathogenesis of vascular cognitive impairment (VCI). In recent years, endothelial cell senescence has emerged as a potential mechanism contributing to microvascular pathologies opening the avenue to the therapeutic exploitation of senolytic drugs in preclinical studies. However, difficulties with the detection of senescent endothelial cells in wild type mouse models of aging hinder the assessment of the efficiency of senolytic treatments. To detect senescent endothelial cells in the aging mouse brain, we analyzed 4233 cells in fractions enriched for cerebromicrovascular endothelial cells and other cells associated with the neurovascular unit obtained from young (3-month-old) and aged (28-month-old) C57BL/6 mice. We define 13 transcriptomic cell types by deep, single-cell RNA sequencing. We match transcriptomic signatures of cellular senescence to endothelial cells identified on the basis of their gene expression profile. Our study demonstrates that with advanced aging, there is an increased ratio of senescent endothelial cells (~ 10%) in the mouse cerebral microcirculation. We propose that our single-cell RNA sequencing-based method can be adapted to study the effect of aging on senescence in various brain cell types as well as to evaluate the efficiency of various senolytic regimens in multiple tissues.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Aging
Blood-brain barrier
Geroscience
Senescence
Vascular cognitive impairment
Megjelenés:GeroScience. - 42 : 2 (2020), p. 429-444. -
További szerzők:Nyúl-Tóth Ádám Balasubramanian, Priya Tarantini, Stefano Ahire, Chetan DelFavero, Jordan Yabluchanskiy, Andriy Csípő Tamás (1990-) Farkas Eszter Wiley, Graham Garman, Lori Csiszár Anna Ungvári Zoltán
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

6.

001-es BibID:BIBFORM099925
035-os BibID:(WOS)000516267700001 (Scopus)85079528822
Első szerző:Kiss Tamás (vegyész)
Cím:Nicotinamide mononucleotide (NMN) supplementation promotes neurovascular rejuvenation in aged mice : transcriptional footprint of SIRT1 activation, mitochondrial protection, anti-inflammatory, and anti-apoptotic effects / Kiss Tamas, Nyúl-Tóth Ádám, Balasubramanian Priya, Tarantini Stefano, Ahire Chetan, Yabluchanskiy Andriy, Csipo Tamas, Farkas Eszter, Wren Jonathan D., Garman Lori, Csiszar Anna, Ungvari Zoltan
Dátum:2020
ISSN:2509-2715 2509-2723
Megjegyzések:Aging-induced structural and functional alterations of the neurovascular unit lead to impairment of neurovascular coupling responses, dysregulation of cerebral blood flow, and increased neuroinflammation, all of which contribute importantly to the pathogenesis of age-related vascular cognitive impairment (VCI). There is increasing evidence showing that a decrease in NAD+ availability with age plays a critical role in age-related neurovascular and cerebromicrovascular dysfunction. Our recent studies demonstrate that restoring cellular NAD+ levels in aged mice rescues neurovascular function, increases cerebral blood flow, and improves performance on cognitive tasks. To determine the effects of restoring cellular NAD+ levels on neurovascular gene expression profiles, 24-month-old C57BL/6 mice were treated with nicotinamide mononucleotide (NMN), a key NAD+ intermediate, for 2 weeks. Transcriptome analysis of preparations enriched for cells of the neurovascular unit was performed by RNA-seq. Neurovascular gene expression signatures in NMN-treated aged mice were compared with those in untreated young and aged control mice. We identified 590 genes differentially expressed in the aged neurovascular unit, 204 of which are restored toward youthful expression levels by NMN treatment. The transcriptional footprint of NMN treatment indicates that increased NAD+ levels promote SIRT1 activation in the neurovascular unit, as demonstrated by analysis of upstream regulators of differentially expressed genes as well as analysis of the expression of known SIRT1-dependent genes. Pathway analysis predicts that neurovascular protective effects of NMN are mediated by the induction of genes involved in mitochondrial rejuvenation, anti-inflammatory, and anti-apoptotic pathways. In conclusion, the recently demonstrated protective effects of NMN treatment on neurovascular function can be attributed to multifaceted sirtuin-mediated anti-aging changes in the neurovascular transcriptome. Our present findings taken together with the results of recent studies using mitochondria-targeted interventions suggest that mitochondrial rejuvenation is a critical mechanism to restore neurovascular health and improve cerebral blood flow in aging.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Aging
Geroscience
Mitochondria dysfunction
Transcriptomics
Vascular cognitive impairment
Megjelenés:GeroScience. - 42 : 2 (2020), p. 527-546. -
További szerzők:Nyúl-Tóth Ádám Balasubramanian, Priya Tarantini, Stefano Ahire, Chetan Yabluchanskiy, Andriy Csípő Tamás (1990-) Farkas Eszter Wren, Jonathan D. Garman, Lori Csiszár Anna Ungvári Zoltán
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

7.

001-es BibID:BIBFORM099946
035-os BibID:(WOS)000492656400001 (Scopus)85074498620
Első szerző:Ungvári Zoltán
Cím:Nrf2 dysfunction and impaired cellular resilience to oxidative stressors in the aged vasculature : from increased cellular senescence to the pathogenesis of age-related vascular diseases / Ungvari Zoltan, Tarantini Stefano, Nyúl-Tóth Ádám, Kiss Tamas, Yabluchanskiy Andriy, Csipo Tamas, Balasubramanian Priya, Lipecz Agnes, Benyo Zoltan, Csiszar Anna
Dátum:2019
ISSN:2509-2715 2509-2723
Megjegyzések:Aging is associated with increased oxidative stress in vascular endothelial and smooth muscle cells, which contribute to the development of a wide range of diseases affecting the circulatory system in older adults. There is growing evidence that in addition to increased production of reactive oxygen species (ROS), aging critically impairs pathways determining cellular resilience to oxidative stressors. In young organisms, the evolutionarily conserved nuclear factor-erythroid-2-related factor 2 (Nrf2)-mediated antioxidant response pathway maintains cellular reduction-oxidation homeostasis and promotes a youthful cellular phenotype by regulating the transcription of an array of cytoprotective (antioxidant, pro-survival, anti-inflammatory and macromolecular damage repair) genes. A critical mechanism by which increased ROS production and Nrf2 dysfunction promote vascular aging and exacerbate pathogenesis of age-related vascular diseases is induction of cellular senescence, an evolutionarily conserved cellular stress response mechanism. Senescent cells cease dividing and undergo distinctive phenotypic alterations, contributing to impairment of angiogenic processes, chronic sterile inflammation, remodeling of the extracellular matrix, and barrier dysfunction. Herein, we review mechanisms contributing to dysregulation of Nrf2-driven cytoprotective responses in the aged vasculature and discuss the multifaceted role of Nrf2 dysfunction in the genesis of age-related pathologies affecting the circulatory system, including its role in induction of cellular senescence. Therapeutic strategies that restore Nrf2 signaling and improve vascular resilience in aging are explored to reduce cardiovascular mortality and morbidity in older adults.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Antioxidant
Atherosclerosis
Nrf2 deficiency
Nrf2 dysfunction
Oxidative stress
Reactive oxygen species
Senescence
Stress resistance
Vascular aging
Vascular cognitive impairment
Megjelenés:GeroScience. - 41 : 6 (2019), p. 727-738. -
További szerzők:Tarantini, Stefano Nyúl-Tóth Ádám Kiss Tamás (1950-) (vegyész) Yabluchanskiy, Andriy Csípő Tamás (1990-) Balasubramanian, Priya Lipécz Ágnes Benyó Zoltán Csiszár Anna
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

8.

001-es BibID:BIBFORM099945
035-os BibID:(WOS)000492573700002 (Scopus)85074572605
Első szerző:Wiedenhoeft, Tabea
Cím:Fusogenic liposomes effectively deliver resveratrol to the cerebral microcirculation and improve endothelium-dependent neurovascular coupling responses in aged mice / Wiedenhoeft Tabea, Tarantini Stefano, Nyúl-Tóth Ádám, Yabluchanskiy Andriy, Csipo Tamas, Balasubramanian Priya, Lipecz Agnes, Kiss Tamas, Csiszar Anna, Csiszar Agnes, Ungvari Zoltan
Dátum:2019
ISSN:2509-2715 2509-2723
Megjegyzések:Adjustment of cerebral blood flow (CBF) to the increased oxygen and nutrient demands of active brain regions via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In advanced age, cerebromicrovascular oxidative stress and endothelial dysfunction impair neurovascular coupling, contributing to age-related cognitive decline. Recently we developed a resveratrol (3,4',5-trihydroxystilbene)-containing fusogenic liposome (FL-RSV)-based molecular delivery system that can effectively target cultured cerebromicrovascular endothelial cells, attenuating age-related oxidative stress. To assess the cerebromicrovascular protective effects of FL-RSV in vivo, aged (24-month-old) C57BL/6 mice were treated with FL-RSV for four days. To demonstrate effective cellular uptake of FL-RSV, accumulation of the lipophilic tracer dyes in cells of the neurovascular unit was confirmed using two-photon imaging (through a chronic cranial window). NVC was assessed by measuring CBF responses (laser speckle contrast imaging) evoked by contralateral whisker stimulation. We found that NVC responses were significantly impaired in aged mice. Treatment with FL-RSV significantly improved NVC responses by increasing NO-mediated vasodilation. These findings are paralleled by the protective effects of FL-RSV on endothelium-dependent relaxation in the aorta. Thus, treatment with FL-RSV rescues endothelial function and NVC responses in aged mice. We propose that resveratrol containing fusogenic liposomes could also be used for combined delivery of various anti-geronic factors, including proteins, small molecules, DNA vectors and mRNAs targeting key pathways involved in microvascular aging and neurovascular dysfunction for the prevention/treatment of age-related cerebromicrovascular pathologies and development of vascular cognitive impairment (VCI) in aging.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Aging
Cerebral circulation
Endothelial dysfunction
Endothelium
Functional hyperemia
Fusogenic liposomes
Oxidative stress
Resveratrol
Vascular cognitive impairment
Megjelenés:GeroScience. - 41 : 6 (2019), p. 711-725. -
További szerzők:Tarantini, Stefano Nyúl-Tóth Ádám Yabluchanskiy, Andriy Csípő Tamás (1990-) Balasubramanian, Priya Lipécz Ágnes Kiss Tamás (1950-) (vegyész) Csiszár Anna Csiszár Ágnes Ungvári Zoltán
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

9.

001-es BibID:BIBFORM099928
035-os BibID:(WOS)000516499100001 (Scopus)85078289607
Első szerző:Yabluchanskiy, Andriy
Cím:Pharmacological or genetic depletion of senescent astrocytes prevents whole brain irradiation-induced impairment of neurovascular coupling responses protecting cognitive function in mice / Yabluchanskiy Andriy, Tarantini Stefano, Balasubramanian Priya, Kiss Tamas, Csipo Tamas, Fülöp Gábor A., Lipecz Agnes, Ahire Chetan, DelFavero Jordan, Nyul-Toth Adam, Sonntag William E., Schwartzman Michal L., Campisi Judith, Csiszar Anna, Ungvari Zoltan
Dátum:2020
ISSN:2509-2715 2509-2723
Megjegyzések:Whole brain irradiation (WBI, also known as whole brain radiation therapy or WBRT) is a mainstream therapy for patients with identifiable brain metastases and as a prophylaxis for microscopic malignancies. WBI accelerates brain aging, causing progressive cognitive dysfunction in ~ 50% of surviving patients, thus compromising quality of life. The mechanisms responsible for this WBI side effect remain obscure, and there are no effective treatments or prevention strategies. Here, we test the hypothesis that WBI induces astrocyte senescence, which contributes to impaired astrocytic neurovascular coupling (NVC) responses and the genesis of cognitive decline. To achieve this goal, we used transgenic p16-3MR mice, which allows the detection and selective elimination of senescent cells. We subjected these mice to a clinically relevant protocol of fractionated WBI (5 Gy twice weekly for 4 weeks). WBI-treated and control mice were tested for spatial memory performance (radial arm water maze), astrocyte-dependent NVC responses (whisker-stimulation-induced increases in cerebral blood flow, assessed by laser speckle contrast imaging), NVC-related gene expression, astrocytic release of eicosanoid gliotransmitters and the presence of senescent astrocytes (by flow cytometry, immunohistochemistry and gene expression profiling) at 6 months post-irradiation. WBI induced senescence in astrocytes, which associated with NVC dysfunction and impaired performance on cognitive tasks. To establish a causal relationship between WBI-induced senescence and NVC dysfunction, senescent cells were depleted from WBI-treated animals (at 3 months post-WBI) by genetic (ganciclovir treatment) or pharmacological (treatment with the BCL-2/BCL-xL inhibitor ABT263/Navitoclax, a known senolytic drug) means. In WBI-treated mice, both treatments effectively eliminated senescent astrocytes, rescued NVC responses, and improved cognitive performance. Our findings suggest that the use of senolytic drugs can be a promising strategy for preventing the cognitive impairment associated with WBI.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Aging
Dementia
Functional hyperemia
Radiation
Senescence
Vascular cognitive impairment
WBI
WBRT
Whole brain radiation therapy
Megjelenés:GeroScience. - 42 : 2 (2020), p. 409-428. -
További szerzők:Tarantini, Stefano Balasubramanian, Priya Kiss Tamás (1950-) (vegyész) Csípő Tamás (1990-) Fülöp Gábor Áron (1988-) (általános orvos) Lipécz Ágnes Ahire, Chetan DelFavero, Jordan Nyúl-Tóth Ádám Sonntag, William E. Schwartzman, Michal L. Campisi, Judith Csiszár Anna Ungvári Zoltán
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Rekordok letöltése1