دورية أكاديمية
أعرض في EDS

tPA supplementation preserves neurovascular and cognitive function in Tg2576 mice.

التفاصيل البيبلوغرافية
العنوان: tPA supplementation preserves neurovascular and cognitive function in Tg2576 mice.
المؤلفون: Uekawa K; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA., Anfray A; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA., Ahn SJ; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA., Casey N; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA., Seo J; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA., Zhou P; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA., Iadecola C; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA., Park L; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA.
المصدر: Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2024 Jul; Vol. 20 (7), pp. 4572-4582. Date of Electronic Publication: 2024 Jun 20.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: John Wiley & Sons, Ltd Country of Publication: United States NLM ID: 101231978 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-5279 (Electronic) Linking ISSN: 15525260 NLM ISO Abbreviation: Alzheimers Dement Subsets: MEDLINE
أسماء مطبوعة: Publication: 2020- : Hoboken, NJ : John Wiley & Sons, Ltd.
Original Publication: Orlando, FL : Elsevier, Inc.
مواضيع طبية MeSH: Tissue Plasminogen Activator*/pharmacology , Mice, Transgenic* , Cerebrovascular Circulation*/drug effects , Cerebrovascular Circulation*/physiology , Disease Models, Animal* , Amyloid beta-Peptides*/metabolism, Animals ; Mice ; Cerebral Amyloid Angiopathy/drug therapy ; Brain/drug effects ; Brain/pathology ; Cognitive Dysfunction/drug therapy ; Cognition/drug effects ; Administration, Intranasal ; Alzheimer Disease/drug therapy ; Nesting Behavior/drug effects ; Male ; Hyperemia/drug therapy
مستخلص: Introduction: Amyloid beta (Aβ) impairs the cerebral blood flow (CBF) increase induced by neural activity (functional hyperemia). Tissue plasminogen activator (tPA) is required for functional hyperemia, and in mouse models of Aβ accumulation tPA deficiency contributes to neurovascular and cognitive impairment. However, it remains unknown if tPA supplementation can rescue Aβ-induced neurovascular and cognitive dysfunction.
Methods: Tg2576 mice and wild-type littermates received intranasal tPA (0.8 mg/kg/day) or vehicle 5 days a week starting at 11 to 12 months of age and were assessed 3 months later.
Results: Treatment of Tg2576 mice with tPA restored resting CBF, prevented the attenuation in functional hyperemia, and improved nesting behavior. These effects were associated with reduced cerebral atrophy and cerebral amyloid angiopathy, but not parenchymal amyloid.
Discussion: These findings highlight the key role of tPA deficiency in the neurovascular and cognitive dysfunction associated with amyloid pathology, and suggest potential therapeutic strategies involving tPA reconstitution.
Highlights: Amyloid beta (Aβ) induces neurovascular dysfunction and impairs the increase of cerebral blood flow induced by neural activity (functional hyperemia). Tissue plasminogen activator (tPA) deficiency contributes to the neurovascular and cognitive dysfunction caused by Aβ. In mice with florid amyloid pathology intranasal administration of tPA rescues the neurovascular and cognitive dysfunction and reduces brain atrophy and cerebral amyloid angiopathy. tPA deficiency plays a crucial role in neurovascular and cognitive dysfunction induced by Aβ and tPA reconstitution may be of therapeutic value.
(© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
References: Cummings J, Zhou Y, Lee G, Zhong K, Fonseca J, Cheng F. Alzheimer's disease drug development pipeline: 2023. Alzheimers Dement. 2023;9:e12385.
Jucker M, Walker LC. Alzheimer's disease: from immunotherapy to immunoprevention. Cell. 2023;186:4260‐4270.
Self WK, Holtzman DM. Emerging diagnostics and therapeutics for Alzheimer disease. Nat Med. 2023;29:2187‐2199.
Apatiga‐Perez R, Soto‐Rojas LO, Campa‐Cordoba BB, et al. Neurovascular dysfunction and vascular amyloid accumulation as early events in Alzheimer's disease. Metab Brain Dis. 2022;37:39‐50.
Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80:844‐866.
Koizumi K, Wang G, Park L. Endothelial dysfunction and amyloid‐beta‐induced neurovascular alterations. Cell Mol Neurobiol. 2016;36:155‐165.
Scheltens P, De Strooper B, Kivipelto M, et al. Alzheimer's disease. Lancet. 2021;397:1577‐1590.
Iturria‐Medina Y, Sotero RC, Toussaint PJ, Mateos‐Perez JM, Evans AC, Alzheimer's Disease Neuroimaging I. Early role of vascular dysregulation on late‐onset Alzheimer's disease based on multifactorial data‐driven analysis. Nat Commun. 2016;7:11934.
Schaeffer S, Iadecola C. Revisiting the neurovascular unit. Nat Neurosci. 2021;24:1198‐1209.
Iadecola C, Zhang F, Niwa K, et al. SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein. Nat Neurosci. 1999;2:157‐161.
Niwa K, Younkin L, Ebeling C, et al. Abeta 1‐40‐related reduction in functional hyperemia in mouse neocortex during somatosensory activation. Proc Natl Acad Sci USA. 2000;97:9735‐9740.
Nortley R, Korte N, Izquierdo P, et al. Amyloid beta oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes. Science. 2019;365:eaav9518.
Park L, Gallo EF, Anrather J, et al. Key role of tissue plasminogen activator in neurovascular coupling. Proc Natl Acad Sci USA. 2008;105:1073‐1078.
Park L, Zhou J, Koizumi K, et al. tPA deficiency underlies neurovascular coupling dysfunction by amyloid‐beta. J Neurosci. 2020;40:8160‐8173.
Tong XK, Lecrux C, Rosa‐Neto P, Hamel E. Age‐dependent rescue by simvastatin of Alzheimer's disease cerebrovascular and memory deficits. J Neurosci. 2012;32:4705‐4715.
Gonias SL. Plasminogen activator receptor assemblies in cell signaling, innate immunity, and inflammation. Am J Physiol Cell Physiol. 2021;321:C721‐C734.
Henderson SJ, Weitz JI, Kim PY. Fibrinolysis: strategies to enhance the treatment of acute ischemic stroke. J Thromb Haemost. 2018;16:1932‐1940.
Thiebaut AM, Gauberti M, Ali C, et al. The role of plasminogen activators in stroke treatment: fibrinolysis and beyond. Lancet Neurol. 2018;17:1121‐1132.
Anfray A, Drieu A, Hingot V, et al. Circulating tPA contributes to neurovascular coupling by a mechanism involving the endothelial NMDA receptors. J Cereb Blood Flow Metab. 2020;40(10):2038‐2054.
Attwell D, Buchan AM, Charpak S, Lauritzen M, Macvicar BA, Newman EA. Glial and neuronal control of brain blood flow. Nature. 2010;468:232‐243.
Baranes D, Lederfein D, Huang YY, Chen M, Bailey CH, Kandel ER. Tissue plasminogen activator contributes to the late phase of LTP and to synaptic growth in the hippocampal mossy fiber pathway. Neuron. 1998;21:813‐825.
Diaz A, Jeanneret V, Merino P, McCann P, Yepes M. Tissue‐type plasminogen activator regulates p35‐mediated Cdk5 activation in the postsynaptic terminal. J Cell Sci. 2019;132:jcs224196.
Qian Z, Gilbert ME, Colicos MA, Kandel ER, Kuhl D. Tissue‐plasminogen activator is induced as an immediate‐early gene during seizure, kindling and long‐term potentiation. Nature. 1993;361:453‐457.
Samson AL, Medcalf RL. Tissue‐type plasminogen activator: a multifaceted modulator of neurotransmission and synaptic plasticity. Neuron. 2006;50:673‐678.
Echagarruga CT, Gheres KW, Norwood JN. Drew PJ. nNOS‐expressing interneurons control basal and behaviorally evoked arterial dilation in somatosensory cortex of mice. eLife. 2020;9:e60533.
O'Gallagher K, Rosentreter RE, Elaine Soriano J, et al. The effect of a neuronal nitric oxide synthase inhibitor on neurovascular regulation in humans. Circ Res. 2022;131:952‐961.
Hosford PS, Gourine AV. What is the key mediator of the neurovascular coupling response? Neurosci Biobehav Rev. 2019;96:174‐181.
Cholet N, Seylaz J, Lacombe P, Bonvento G. Local uncoupling of the cerebrovascular and metabolic responses to somatosensory stimulation after neuronal nitric oxide synthase inhibition. J Cereb Blood Flow Metab. 1997;17:1191‐1201.
Cacquevel M, Launay S, Castel H, et al. Ageing and amyloid‐beta peptide deposition contribute to an impaired brain tissue plasminogen activator activity by different mechanisms. Neurobiol Dis. 2007;27:164‐173.
Jacobsen JS, Comery TA, Martone RL, Elokdah H, Crandall DL, Oganesian A, et al. Enhanced clearance of Abeta in brain by sustaining the plasmin proteolysis cascade. Proc Natl Acad Sci USA. 2008;105:8754‐8759.
Melchor JP, Pawlak R, Strickland S. The tissue plasminogen activator‐plasminogen proteolytic cascade accelerates amyloid‐beta (Abeta) degradation and inhibits Abeta‐induced neurodegeneration. J Neurosci. 2003;23:8867‐8871.
Dotti CG, Galvan C, Ledesma MD. Plasmin deficiency in Alzheimer's disease brains: causal or casual? Neurodegener Dis. 2004;1:205‐212.
Sutton R, Keohane ME, VanderBerg SR, Gonias SL. Plasminogen activator inhibitor‐1 in the cerebrospinal fluid as an index of neurological disease. Blood Coagul Fibrinolysis. 1994;5:167‐171.
Chen N, Chopp M, Xiong Y, et al. Subacute intranasal administration of tissue plasminogen activator improves stroke recovery by inducing axonal remodeling in mice. Exp Neurol. 2018;304:82‐89.
Dong Y, Hong W, Tang Z, Gao Y, Wu X, Liu H. Sevoflurane leads to learning and memory dysfunction via breaking the balance of tPA/PAI‐1. Neurochem Int. 2020;139:104789.
Fonseca LC, Lopes JA, Vieira J, et al. Intranasal drug delivery for treatment of Alzheimer's disease. Drug Deliv Transl Res. 2021;11:411‐425.
Liu Z, Li Y, Zhang L, et al. Subacute intranasal administration of tissue plasminogen activator increases functional recovery and axonal remodeling after stroke in rats. Neurobiol Dis. 2012;45:804‐809.
Pu H, Shi Y, Zhang L, Lu Z, Ye Q, Leak RK, et al. Protease‐independent action of tissue plasminogen activator in brain plasticity and neurological recovery after ischemic stroke. Proc Natl Acad Sci USA. 2019;116:9115‐9124.
Xia Y, Pu H, Leak RK, et al. Tissue plasminogen activator promotes white matter integrity and functional recovery in a murine model of traumatic brain injury. Proc Natl Acad Sci USA. 2018;115:E9230‐E9238.
Hsiao K, Chapman P, Nilsen S, et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science. 1996;274:99‐102.
Park L, Zhou J, Zhou P, et al. Innate immunity receptor CD36 promotes cerebral amyloid angiopathy. Proc Natl Acad Sci USA. 2013;110:3089‐3094.
Park L, Zhou P, Pitstick R, et al. Nox2‐derived radicals contribute to neurovascular and behavioral dysfunction in mice overexpressing the amyloid precursor protein. Proc Natl Acad Sci USA. 2008;105:1347‐1352.
Uekawa K, Hattori Y, Ahn SJ, et al. Border‐associated macrophages promote cerebral amyloid angiopathy and cognitive impairment through vascular oxidative stress. Mol Neurodegener. 2023;18:73.
Park L, Hochrainer K, Hattori Y, et al. Tau induces PSD95‐neuronal NOS uncoupling and neurovascular dysfunction independent of neurodegeneration. Nat Neurosci. 2020;23:1079‐1089.
Paxinos G, Franklin KBJ. The Mouse Brain in Stereotaxic Coordinates. Elsevier Academic Press; 2004.
Iadecola C. Nitric oxide participates in the cerebrovasodilation elicited from cerebellar fastigial nucleus. Am J Physiol. 1992;263:R1156‐R1161.
Santisteban MM, Ahn SJ, Lane D, et al. Endothelium‐macrophage crosstalk mediates blood‐brain barrier dysfunction in hypertension. Hypertension. 2020;76:795‐807.
Deacon RM. Assessing nest building in mice. Nat Protoc. 2006;1:1117‐1119.
Nemeth E, Ganz T. Hepcidin and iron in health and disease. Annu Rev Med. 2023;74:261‐277.
Greenberg SM, Bacskai BJ, Hernandez‐Guillamon M, Pruzin J, Sperling R, van Veluw SJ. Cerebral amyloid angiopathy and Alzheimer disease—one peptide, two pathways. Nat Rev Neurol. 2020;16:30‐42.
Iadecola C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron. 2017;96:17‐42.
Wu F, Torre E, Cuellar‐Giraldo D, et al. Tissue‐type plasminogen activator triggers the synaptic vesicle cycle in cerebral cortical neurons. J Cereb Blood Flow Metab. 2015;35:1966‐1976.
Yepes M, Wu F, Torre E, Cuellar‐Giraldo D, Jia D, Cheng L. Tissue‐type plasminogen activator induces synaptic vesicle endocytosis in cerebral cortical neurons. Neuroscience. 2016;319:69‐78.
Lochner JE, Honigman LS, Grant WF, et al. Activity‐dependent release of tissue plasminogen activator from the dendritic spines of hippocampal neurons revealed by live‐cell imaging. J Neurobiol. 2006;66:564‐577.
Janik R, Thomason LA, Chaudhary S, et al. Attenuation of functional hyperemia to visual stimulation in mild Alzheimer's disease and its sensitivity to cholinesterase inhibition. Biochim Biophys Acta. 2016;1862:957‐965.
McDade E, Kim A, James J, et al. Cerebral perfusion alterations and cerebral amyloid in autosomal dominant Alzheimer disease. Neurology. 2014;83:710‐717.
Ruitenberg A, den Heijer T, Bakker SL, et al. Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol. 2005;57:789‐794.
Swinford CG, Risacher SL, Wu YC, et al. Altered cerebral blood flow in older adults with Alzheimer's disease: a systematic review. Brain Imaging Behav. 2023;17:223‐256.
Tomoto T, Tarumi T, Chen J, Pasha EP, Cullum CM, Zhang R. Cerebral vasomotor reactivity in amnestic mild cognitive impairment. J Alzheimers Dis. 2020;77:191‐202.
Tarasoff‐Conway JM, Carare RO, Osorio RS, et al. Clearance systems in the brain‐implications for Alzheimer disease. Nat Rev Neurol. 2015;11:457‐470.
Holstein‐Ronsbo S, Gan Y, Giannetto MJ, et al. Glymphatic influx and clearance are accelerated by neurovascular coupling. Nat Neurosci. 2023;26:1042‐1053.
Weller RO, Sharp MM, Christodoulides M, Carare RO, Mollgard K. The meninges as barriers and facilitators for the movement of fluid, cells and pathogens related to the rodent and human CNS. Acta Neuropathol. 2018;135:363‐385.
Badimon A, Torrente D, Norris EH. Vascular dysfunction in Alzheimer's disease: alterations in the plasma contact and fibrinolytic systems. Int J Mol Sci. 2023;24:7046.
Kingston IB, Castro MJ, Anderson S. In vitro stimulation of tissue‐type plasminogen activator by Alzheimer amyloid beta‐peptide analogues. Nat Med. 1995;1:138‐142.
Rodriguez G, Eren M, Haupfear I, et al. Pharmacological inhibition of plasminogen activator inhibitor‐1 prevents memory deficits and reduces neuropathology in APP/PS1 mice. Psychopharmacology. 2023;240:2641‐2655.
Tucker HM, Kihiko M, Caldwell JN, et al. The plasmin system is induced by and degrades amyloid‐beta aggregates. J Neurosci. 2000;20:3937‐3946.
Filippi M, Cecchetti G, Spinelli EG, Vezzulli P, Falini A, Agosta F. Amyloid‐Related imaging abnormalities and beta‐amyloid‐targeting antibodies: a systematic review. JAMA Neurol. 2022;79:291‐304.
Hampel H, Elhage A, Cho M, Apostolova LG, Nicoll JAR, Atri A. Amyloid‐related imaging abnormalities (ARIA): radiological, biological and clinical characteristics. Brain. 2023;146:4414‐4424.
van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer's disease. N Engl J Med. 2023;388:9‐21.
Sims JR, Zimmer JA, Evans CD, et al. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER‐ALZ 2 randomized clinical trial. JAMA. 2023;330:512‐527.
Adibhatla RM, Hatcher JF. Tissue plasminogen activator (tPA) and matrix metalloproteinases in the pathogenesis of stroke: therapeutic strategies. CNS Neurol Disord Drug Targets. 2008;7:243‐253.
Lapchak PA, Chapman DF, Zivin JA. Metalloproteinase inhibition reduces thrombolytic (tissue plasminogen activator)‐induced hemorrhage after thromboembolic stroke. Stroke. 2000;31:3034‐3040.
Reish NJ, Jamshidi P, Stamm B, et al. Multiple cerebral hemorrhages in a patient receiving lecanemab and treated with t‐PA for stroke. N Engl J Med. 2023;388:478‐479.
Olson ST, Swanson R, Day D, Verhamme I, Kvassman J, Shore JD. Resolution of Michaelis complex, acylation, and conformational change steps in the reactions of the serpin, plasminogen activator inhibitor‐1, with tissue plasminogen activator and trypsin. Biochemistry. 2001;40:11742‐11756.
Yi JS, Kim YH, Koh JY. Infarct reduction in rats following intraventricular administration of either tissue plasminogen activator (tPA) or its non‐protease mutant S478A‐tPA. Exp Neurol. 2004;189:354‐360.
معلومات مُعتمدة: BrightFocus Foundation; R01 NS037853 United States NS NINDS NIH HHS; R01 NS097805 United States NS NINDS NIH HHS; Feil Family Foundation; 17528 United Kingdom CRUK_ Cancer Research UK; R01-NS097805 United States GF NIH HHS; Leon Levy Foundation; R01-NS37853 United States GF NIH HHS
فهرسة مساهمة: Keywords: amyloid beta; atrophy; cerebral amyloid angiopathy; dementia; functional hyperemia; neuroinflammation
المشرفين على المادة: EC 3.4.21.68 (Tissue Plasminogen Activator)
0 (Amyloid beta-Peptides)
تواريخ الأحداث: Date Created: 20240620 Date Completed: 20240715 Latest Revision: 20240731
رمز التحديث: 20240731
مُعرف محوري في PubMed: PMC11247712
DOI: 10.1002/alz.13878
PMID: 38899570
قاعدة البيانات: MEDLINE
الوصف
تدمد:1552-5279
DOI:10.1002/alz.13878