Hệ thống thoát dịch ngoại vi bị suy giảm trong não chuột già và trong sự hiện diện của bệnh mạch máu amyloid não

Springer Science and Business Media LLC - Tập 121 - Trang 431-443 - 2011
Cheryl A. Hawkes1, Wolfgang Härtig2, Johannes Kacza3, Reinhard Schliebs2, Roy O. Weller1, James A. Nicoll1, Roxana O. Carare1
1Division of Clinical Neurosciences, Southampton General Hospital, University of Southampton, Southampton, UK
2Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany
3Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany

Tóm tắt

Sự lắng đọng của peptide amyloid-β (Aβ) trong thành mạch máu màng mềm và vỏ não, được gọi là bệnh mạch máu amyloid não (CAA), xuất hiện trong quá trình lão hóa bình thường và ở hầu hết các trường hợp bệnh Alzheimer (AD). Việc thiếu hụt các cơ chế làm sạch để loại bỏ Aβ khỏi não đã góp phần vào sự phát triển của CAA và AD dạng sporadic. Ở đây, chúng tôi đã điều tra tác động của CAA và quá trình lão hóa lên mô hình thoát dịch ngoại vi của các chất trong não của chuột naif và ở mô hình chuột Tg2576 của bệnh AD. Chúng tôi báo cáo rằng quá trình thoát dịch của dextran trọng lượng phân tử nhỏ dọc theo màng đáy mạch máu bị suy giảm ở các mao mạch và động mạch vùng hải mã của chuột hoang dã 22 tháng tuổi so với các động vật 3 và 7 tháng tuổi, điều này liên quan đến sự thay đổi mật độ mao mạch theo tuổi tác. Các biến đổi liên quan đến tuổi tác trong mức độ laminin, fibronectin và perlecan trong các màng đáy mạch cũng được ghi nhận ở chuột hoang dã. Hơn nữa, dextran đã được quan sát thấy trong thành mạch của các chuột Tg2576 trong sự hiện diện của CAA, cho thấy rằng sự lắng đọng của Aβ trong thành mạch làm gián đoạn con đường bình thường để loại bỏ các chất từ mô não. Những dữ liệu này hỗ trợ giả thuyết rằng quá trình thoát dịch ngoại vi từ não bị thay đổi cả trong não lão hóa và như một hệ quả của CAA. Những phát hiện này có ý nghĩa đối với thành công của các chiến lược điều trị nhằm điều trị AD dựa trên sức khỏe của mạch máu não khi lão hóa.

Từ khóa

#amyloid-β #bệnh mạch máu amyloid não #tuổi tác #thoát dịch ngoại vi #chuột Tg2576

Tài liệu tham khảo

Ailles L, Kisilevsky R, Young ID (1993) Induction of perlecan gene expression precedes amyloid formation during experimental murine AA amyloidogenesis. Lab Investig 69:443–448 Akima M, Nonaka H, Kagesawa M, Tanaka K (1986) A study on the microvasculature of the cerebral cortex. Fundamental architecture and its senile change in the frontal cortex. Lab Investig 55:482–489 Aumailley M, Krieg T (1996) Laminins: a family of diverse multifunctional molecules of basement membranes. J Investig Dermatol 106:209–214 Bell RD, Zlokovic BV (2009) Neurovascular mechanisms and blood–brain barrier disorder in Alzheimer’s disease. Acta Neuropathol 118:103–113 Boche D, Zotova E, Weller RO, Love S, Neal JW, Pickering RM et al (2008) Consequence of Aβ immunization on the vasculature of human Alzheimer’s disease brain. Brain 131:3299–3310 Bradbury MW, Cserr HF, Westrop RJ (1981) Drainage of cerebral interstitial fluid into deep cervical lymph of the rabbit. Am J Physiol 240:F329–F336 Bronfman FC, Alvarez A, Morgan C, Inestrosa NC (1998) Laminin blocks the assembly of wild-type Aβ and the Dutch variant peptide into Alzheimer’s fibrils. Amyloid 5:16–23 Bronfman FC, Garrido J, Alvarez A, Morgan C, Inestrosa NC (1996) Laminin inhibits amyloid-beta-peptide fibrillation. Neurosci Lett 218:201–203 Burger S, Noack M, Kirazov LP, Kirazov EP, Naydenov CL, Kouznetsova E et al (2009) Vascular endothelial growth factor (VEGF) affects processing of amyloid precursor protein and beta-amyloidogenesis in brain slice cultures derived from transgenic Tg2576 mouse brain. Int J Dev Neurosci 27:517–523 Burns EM, Kruckeberg TW, Gaetano PK (1981) Changes with age in cerebral capillary morphology. Neurobiol Aging 2:283–291 Calhoun ME, Burgermeister P, Phinney AL, Stalder M, Tolnay M, Wiederhold KH et al (1999) Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid. Proc Natl Acad Sci USA 96:14088–14093 Carare RO, Bernardes-Silva M, Newman TA, Page AM, Nicoll JA, Perry VH et al (2008) Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology. Neuropathol Appl Neurobiol 34:131–144 Castillo GM, Ngo C, Cummings J, Wight TN, Snow AD (1997) Perlecan binds to the beta-amyloid proteins (Aβ) of Alzheimer’s disease, accelerates Aβ fibril formation, and maintains Aβ fibril stability. J Neurochem 69:2452–2465 Christie R, Yamada M, Moskowitz M, Hyman B (2001) Structural and functional disruption of vascular smooth muscle cells in a transgenic mouse model of amyloid angiopathy. Am J Pathol 158:1065–1071 Chung YA, O JH, Kim JY, Kim KJ, Ahn KJ (2009) Hypoperfusion and ischemia in cerebral amyloid angiopathy documented by 99mTc-ECD brain perfusion SPECT. J Nucl Med 50:1969–1974 Costell M, Gustafsson E, Aszodi A, Morgelin M, Bloch W, Hunziker E et al (1999) Perlecan maintains the integrity of cartilage and some basement membranes. J Cell Biol 147:1109–1122 Cotman SL, Halfter W, Cole GJ (2000) Agrin binds to beta-amyloid (Aβ), accelerates Aβ fibril formation, and is localized to Aβ deposits in Alzheimer’s disease brain. Mol Cell Neurosci 15:183–198 Couchman JR, Abrahamson DR, McCarthy KJ (1993) Basement membrane proteoglycans and development. Kidney Int 43:79–84 Deane R, Zlokovic BV (2007) Role of the blood–brain barrier in the pathogenesis of Alzheimer’s disease. Curr Alzheimer Res 4:191–197 Domnitz SB, Robbins EM, Hoang AW, Garcia-Alloza M, Hyman BT, Rebeck GW et al (2005) Progression of cerebral amyloid angiopathy in transgenic mouse models of Alzheimer disease. J Neuropathol Exp Neurol 64:588–594 Erickson AC, Couchman JR (2000) Still more complexity in mammalian basement membranes. J Histochem Cytochem 48:1291–1306 Haglund M, Kalaria R, Slade JY, Englund E (2006) Differential deposition of amyloid beta peptides in cerebral amyloid angiopathy associated with Alzheimer’s disease and vascular dementia. Acta Neuropathol 111:430–435 Han BH, Zhou ML, Abousaleh F, Brendza RP, Dietrich HH, Koenigsknecht-Talboo J et al (2008) Cerebrovascular dysfunction in amyloid precursor protein transgenic mice: contribution of soluble and insoluble amyloid-beta peptide, partial restoration via gamma-secretase inhibition. J Neurosci 28:13542–13550 Hicks P, Rolsten C, Brizzee D, Samorajski T (1983) Age-related changes in rat brain capillaries. Neurobiol Aging 4:69–75 Hooijmans CR, Graven C, Dederen PJ, Tanila H, van Groen T, Kiliaan AJ (2007) Amyloid beta deposition is related to decreased glucose transporter-1 levels and hippocampal atrophy in brains of aged APP/PS1 mice. Brain Res 1181:93–103 Hutchins PM, Lynch CD, Cooney PT, Curseen KA (1996) The microcirculation in experimental hypertension and aging. Cardiovasc Res 32:772–780 Ichimura T, Fraser PA, Cserr HF (1991) Distribution of extracellular tracers in perivascular spaces of the rat brain. Brain Res 545:103–113 Jellinger KA, Lauda F, Attems J (2007) Sporadic cerebral amyloid angiopathy is not a frequent cause of spontaneous brain hemorrhage. Eur J Neurol 14:923–928 Kalaria RN (1996) Cerebral vessels in ageing and Alzheimer’s disease. Pharmacol Ther 72:193–214 Kawarabayashi T, Younkin LH, Saido TC, Shoji M, Ashe KH, Younkin SG (2001) Age-dependent changes in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer’s disease. J Neurosci 21:372–381 Kiuchi Y, Isobe Y, Fukushima K (2002) Type IV collagen prevents amyloid beta-protein fibril formation. Life Sci 70:1555–1564 Kiuchi Y, Isobe Y, Fukushima K, Kimura M (2002) Disassembly of amyloid beta-protein fibril by basement membrane components. Life Sci 70:2421–2431 Knox SM, Whitelock JM (2006) Perlecan: how does one molecule do so many things? Cell Mol Life Sci 63:2435–2445 Kouznetsova E, Klingner M, Sorger D, Sabri O, Grossmann U, Steinbach J et al (2006) Developmental and amyloid plaque-related changes in cerebral cortical capillaries in transgenic Tg2576 Alzheimer mice. Int J Dev Neurosci 24:187–193 Krause DL, Muller N (2010) Neuroinflammation, microglia and implications for anti-inflammatory treatment in Alzheimer’s disease. Int J Alzheimers Dis Martin AJ, Friston KJ, Colebatch JG, Frackowiak RS (1991) Decreases in regional cerebral blood flow with normal aging. J Cereb Blood Flow Metab 11:684–689 Massaad CA, Amin SK, Hu L, Mei Y, Klann E, Pautler RG (2010) Mitochondrial superoxide contributes to blood flow and axonal transport deficits in the Tg2576 mouse model of Alzheimer’s disease. PLoS One 5:e10561 Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC et al (2010) Decreased clearance of CNS beta-amyloid in Alzheimer’s disease. Science 330(6012):1774 Miao J, Xu F, Davis J, Otte-Holler I, Verbeek MM, Van Nostrand WE (2005) Cerebral microvascular amyloid beta protein deposition induces vascular degeneration and neuroinflammation in transgenic mice expressing human vasculotropic mutant amyloid beta precursor protein. Am J Pathol 167:505–515 Miners JS, Ashby E, Van Helmond Z, Chalmers KA, Palmer LE, Love S et al (2008) Angiotensin-converting enzyme (ACE) levels and activity in Alzheimer’s disease, and relationship of perivascular ACE-1 to cerebral amyloid angiopathy. Neuropathol Appl Neurobiol 34:181–193 Miners JS, Baig S, Palmer J, Palmer LE, Kehoe PG, Love S (2008) Aβ-degrading enzymes in Alzheimer’s disease. Brain Pathol 18:240–252 Moody DM, Brown WR, Challa VR, Ghazi-Birry HS, Reboussin DM (1997) Cerebral microvascular alterations in aging, leukoaraiosis, and Alzheimer’s disease. Ann NY Acad Sci 826:103–116 Morgan C, Bugueno MP, Garrido J, Inestrosa NC (2002) Laminin affects polymerization, depolymerization and neurotoxicity of Aβ peptide. Peptides 23:1229–1240 Natte R, Maat-Schieman ML, Haan J, Bornebroek M, Roos RA, van Duinen SG (2001) Dementia in hereditary cerebral hemorrhage with amyloidosis-Dutch type is associated with cerebral amyloid angiopathy but is independent of plaques and neurofibrillary tangles. Ann Neurol 50:765–772 Ochi H, Abraham M, Ishikawa H, Frenkel D, Yang K, Basso AS et al (2006) Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+CD25− LAP + T cells. Nat Med 12:627–635 Paris D, Patel N, DelleDonne A, Quadros A, Smeed R, Mullan M (2004) Impaired angiogenesis in a transgenic mouse model of cerebral amyloidosis. Neurosci Lett 366:80–85 Park L, Anrather J, Zhou P, Frys K, Pitstick R, Younkin S et al (2005) NADPH-oxidase-derived reactive oxygen species mediate the cerebrovascular dysfunction induced by the amyloid beta peptide. J Neurosci 25:1769–1777 Patton RL, Kalback WM, Esh CL, Kokjohn TA, Van Vickle GD, Luehrs DC et al (2006) Amyloid-beta peptide remnants in AN-1792-immunized Alzheimer’s disease patients: a biochemical analysis. Am J Pathol 169:1048–1063 Perlmutter LS (1994) Microvascular pathology and vascular basement membrane components in Alzheimer’s disease. Mol Neurobiol 9:33–40 Pfeifer LA, White LR, Ross GW, Petrovitch H, Launer LJ (2002) Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study. Neurology 58:1629–1634 Pfeifer M, Boncristiano S, Bondolfi L, Stalder A, Deller T, Staufenbiel M et al (2002) Cerebral hemorrhage after passive anti-Aβ immunotherapy. Science 298:1379 Preston SD, Steart PV, Wilkinson A, Nicoll JA, Weller RO (2003) Capillary and arterial cerebral amyloid angiopathy in Alzheimer’s disease: defining the perivascular route for the elimination of amyloid beta from the human brain. Neuropathol Appl Neurobiol 29:106–117 Riddle DR, Sonntag WE, Lichtenwalner RJ (2003) Microvascular plasticity in aging. Ageing Res Rev 2:149–168 Schley D, Carare-Nnadi R, Please CP, Perry VH, Weller RO (2006) Mechanisms to explain the reverse perivascular transport of solutes out of the brain. J Theor Biol 238:962–974 Shimizu H, Ghazizadeh M, Sato S, Oguro T, Kawanami O (2009) Interaction between beta-amyloid protein and heparan sulfate proteoglycans from the cerebral capillary basement membrane in Alzheimer’s disease. J Clin Neurosci 16:277–282 Shin HK, Jones PB, Garcia-Alloza M, Borrelli L, Greenberg SM, Bacskai BJ et al (2007) Age-dependent cerebrovascular dysfunction in a transgenic mouse model of cerebral amyloid angiopathy. Brain 130:2310–2319 Steffensen B, Chen Z, Pal S, Mikhailova M, Su J, Wang Y et al (2010) Fragmentation of fibronectin by inherent autolytic and matrix metalloproteinase activities. Matrix Biol Szentistvanyi I, Patlak CS, Ellis RA, Cserr HF (1984) Drainage of interstitial fluid from different regions of rat brain. Am J Physiol 246:F835–F844 Tchougounova E, Forsberg E, Angelborg G, Kjellen L, Pejler G (2001) Altered processing of fibronectin in mice lacking heparin: a role for heparin-dependent mast cell chymase in fibronectin degradation. J Biol Chem 276:3772–3777 Thal DR, Larionov S, Abramowski D, Wiederhold KH, Van Dooren T, Yamaguchi H et al (2007) Occurrence and co-localization of amyloid beta-protein and apolipoprotein E in perivascular drainage channels of wild-type and APP-transgenic mice. Neurobiol Aging 28:1221–1230 Tian J, Shi J, Smallman R, Iwatsubo T, Mann DM (2006) Relationships in Alzheimer’s disease between the extent of Aβ deposition in cerebral blood vessel walls, as cerebral amyloid angiopathy, and the amount of cerebrovascular smooth muscle cells and collagen. Neuropathol Appl Neurobiol 32:332–340 Timpl R (1996) Macromolecular organization of basement membranes. Curr Opin Cell Biol 8:618–624 Topple A, Fifkova E, Cullen-Dockstader K (1990) Effect of age on blood vessels and neurovascular appositions in the rat dentate fascia. Neurobiol Aging 11:371–380 Uspenskaia O, Liebetrau M, Herms J, Danek A, Hamann GF (2004) Aging is associated with increased collagen type IV accumulation in the basal lamina of human cerebral microvessels. BMC Neurosci 5:37 Van Dorpe J, Smeijers L, Dewachter I, Nuyens D, Spittaels K, Van Den Haute C et al (2000) Prominent cerebral amyloid angiopathy in transgenic mice overexpressing the London mutant of human APP in neurons. Am J Pathol 157:1283–1298 van Horssen J, Kleinnijenhuis J, Maass CN, Rensink AA, Otte-Holler I, David G et al (2002) Accumulation of heparan sulfate proteoglycans in cerebellar senile plaques. Neurobiol Aging 23:537–545 van Horssen J, Otte-Holler I, David G, Maat-Schieman ML, van den Heuvel LP, Wesseling P et al (2001) Heparan sulfate proteoglycan expression in cerebrovascular amyloid beta deposits in Alzheimer’s disease and hereditary cerebral hemorrhage with amyloidosis (Dutch) brains. Acta Neuropathol 102:604–614 Weller RO, Boche D, Nicoll JA (2009) Microvasculature changes and cerebral amyloid angiopathy in Alzheimer’s disease and their potential impact on therapy. Acta Neuropathol 118:87–102 Weller RO, Cohen NR, Nicoll JA (2004) Cerebrovascular disease and the pathophysiology of Alzheimer’s disease. Implications for therapy. Panminerva Med 46:239–251 Weller RO, Subash M, Preston SD, Mazanti I, Carare RO (2008) Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer’s disease. Brain Pathol 18:253–266 Wilcock DM, Rojiani A, Rosenthal A, Subbarao S, Freeman MJ, Gordon MN et al (2004) Passive immunotherapy against Aβ in aged APP-transgenic mice reverses cognitive deficits and depletes parenchymal amyloid deposits in spite of increased vascular amyloid and microhemorrhage. J Neuroinflammation 1:24 Wyss-Coray T, Lin C, Sanan DA, Mucke L, Masliah E (2000) Chronic overproduction of transforming growth factor-beta1 by astrocytes promotes Alzheimer’s disease-like microvascular degeneration in transgenic mice. Am J Pathol 156:139–150