Abstract
Astrocytes react to various neurodegenerative insults rapidly and undergo changes known as gliosis or astrogliosis. In Alzheimer’s disease (AD), a wall of reactive astrocytes surrounds senile plaques of β-amyloid (Aβ) and might play an important role in clearing of Aβ. AD is neuropathologically characterized by the co-existence of two pathological structures, senile plaques and neurofibrillary tangles composed of Aβ and Tau protein respectively. However, the molecular mechanisms underlie astrogliosis and increased expressions of GFAP and other astrogliosis markers are poorly understood. Since AD is age related, the aim of this study is to compare the gliosis of aging prone astrocytes cultured from senescence-accelerated mice and astrocytes from normal mice in response to Aβ and Tau treatment. Our results demonstrated that the aging prone astrocytes have showed larger degree of gliosis than normal astrocytes. Since reactive astrocytes had less ability to support co-cultured neurons as compared with control astrocytes. Therefore, it is likely that aging prone astrocytes might contribute to cell loss or dysfunction associated with insults in AD. In other words, aging prone astrocytes might have decreased ability than normal astrocytes to protect or prevent neuronal dysfunction in AD pathology. In addition, further AD related studies should use aging prone astrocytes instead of normal astrocytes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arnold SE, Lee VM, Gur RE, Trojanowski JQ (1991) Abnormal expression of two microtubule-associated proteins (MAP2 and MAP5) in specific subfields of the hippocampal formation in schizophrenia. Proc Natl Acad Sci USA 88:10850–10854. doi:10.1073/pnas.88.23.10850
Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259. doi:10.1007/BF00308809
Burbach GJ, Dehn D, Del Turco D, STaufenbiel M, Deller T (2004) Laser microdissection reveals regional and cellular differences in GFAP mRNA upregulation following brain injury, axonal denervation, and amyloid plaque deposition. Glia 48:76–84. doi:10.1002/glia.20057
Campbell RL, Bruce RD (1981) Comparative dermatotoxicology I direct comparison of rabbit and human primary skin irritation responses to isopropylmyristate. Toxicol Appl Pharmacol 59:555–563. doi:10.1016/0041-008X(81)90310-0
Caputo CB, Sygowski LA, Scott CW, Sobel IR (1992) Role of Tau in the polymerization of peptides from beta-amyloid precursor protein. Brain Res 597:227–232. doi:10.1016/0006-8993(92)91478-W
Cardon LR, Bell JI (2001) Association study designs for complex diseases. Nat Rev Genet 2:91–99. doi:10.1038/35052543
Chen M, Fernandez HL (2004) Stimulation of beta-amyloid precursor protein alpha-processing by phorbol ester involves calcium and calpain activation. Biochem Biophys Res Commun 316:332–340. doi:10.1016/j.bbrc.2004.02.052
Chiarini A, Dal Pra I, Whitfield JF, Armato U (2006) The killing of neurons by beta-amyloid peptides, prions, and pro-inflammatory cytokines. Ital J Anat Embryol 111:221–246
Cocchia D (1981) Immunocytochemical localization of S-100 protein in the brain of adult rat. An ultrastructural study. Cell Tissue Res 214:529–540. doi:10.1007/BF00233493
Cotrina ML, Nedergaard M (2002) Astrocytes in the aging brain. J Neurosci Res 67:1–10. doi:10.1002/jnr.10121
Dehmelt L, Halpain S (2004) Actin and microtubules in neurite initiation: are MAPs the missing link? J Neurobiol 58:18–33. doi:10.1002/neu.10284
Dehmelt L, Halpain S (2005) The MAP2/Tau family of microtubule-associated proteins. Genome Biol 6:204
DeWitt DA, Perry G, Cohen M, Doller C, Silver J (1998) Astrocytes regulate microglial phagocytosis of senile plaque cores of Alzheimer’s disease. Exp Neurol 149:329–355. doi:10.1006/exnr.1997.6738
Eng LF, Ghirnikar RS (1994) GFAP and astrogliosis. Brain Pathol 4:229–237. doi:10.1111/j.1750-3639.1994.tb00838.x
Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochem Res 25:1439–1451. doi:10.1023/A:1007677003387
Esch FS, Keim PS, Beattie EC, Blacher RW, Culwell AR, Oltersdorf T, McClure D, Ward PJ (1990) Cleavage of amyloid beta peptide during constitutive processing of its precursor. Science 248:1122–1124. doi:10.1126/science.2111583
Fauconneau B, Petegnief V, Sanfeliu C, Piriou A, Planas AM (2002) Induction of heat shock proteins (HSPs) by sodium arsenite in cultured astrocytes and reduction of hydrogen peroxide-induced cell death. J Neurochem 83:1338–1348. doi:10.1046/j.1471-4159.2002.01230.x
Finch CE (2003) Neurons, glia, and plasticity in normal brain aging. Neurobiol Aging 24(Suppl 1):S123–S127. doi:10.1016/S0197-4580(03)00051-4
Griffin WS, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, White III CL , Araoz C (1989) Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci USA 86:7611–7615. doi:10.1073/pnas.86.19.7611
Haglid KG, Yang Q, Hamberger A, Bergman S, Widerberg A, Danielsen N (1997) S-100beta stimulates neurite outgrowth in the rat sciatic nerve grafted with acellular muscle transplants. Brain Res 753:196–201. doi:10.1016/S0006-8993(96)01463-1
Harada J, Sugimoto M (1999) Activation of caspase-3 in β-amyloid-induced apoptosis of cultured rat cortical neurons. Brain Res 842:311–323. doi:10.1016/S0006-8993(99)01808-9
Holmes DJ (2003) F344. Rat Sci SAGE KE 36:as2
Hung AY, Haass C, Nitsch RM, Qiu WQ, Citron M, Wurtman RJ, Growdon JH, Selkoe DJ (1993) Activation of protein kinase C inhibits cellular production of the amyloid beta-protein. J Biol Chem 268:22959–22962
Itoh Y, Esaki T, Shimoji K, Cook M, Law MJ, Kaufman E, Sokoloff L (2003) Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo. Proc Natl Acad Sci USA 100:4879–4884. doi:10.1073/pnas.0831078100
Jolly-Tornetta C, Wolf BA (2000) Protein kinase C regulation of intracellular and cell surface amyloid precursor protein (APP) cleavage in CHO695 cells. Biochemistry 39:15282–15290. doi:10.1021/bi001723y
Kerokoski P, Soininen H, Pirttila ÈT (2001) β-amyloid (1–42) affects MTT reduction in astrocytes: implications for vesicular trafficking and cell functionality. Neurochem Int 38:127–134. doi:10.1016/S0197-0186(00)00071-1
Kim C, Jang CH, Bang JH, Jung MW, Joo I, Kim SU, Mook-Jung I (2002) Amyloid precursor protein processing is separately regulated by protein kinase C and tyrosine kinase in human astrocytes. Neurosci Lett 324:185–188. doi:10.1016/S0304-3940(02)00217-3
Kimura N, Negishi T, Ishii Y, Kyuwa S, Yoshikawa Y (2004) Astroglial responses against Abeta initially occur in cerebral primary cortical cultures: species differences between rat and cynomolgus monkey. Neurosci Res 49:339–346. doi:10.1016/j.neures.2004.03.010
Kimura N, Ishii Y, Suzaki S, Negishi T, Kyuwa S, Yoshikawa Y (2007) Abeta upregulates and colocalizes with LGI3 in cultured rat astrocytes. Cell Mol Neurobiol 27:335–350. doi:10.1007/s10571-006-9127-8
Kuperstein F, Reiss N, Koudinova N, Yavin E (2001) Biphasic modulation of protein kinase C and enhanced cell toxicity by amyloid beta peptide and anoxia in neuronal cultures. J Neurochem 76:758–767. doi:10.1046/j.1471-4159.2001.00037.x
Lace GL, Wharton SB, Ince PG (2007) A brief history of tau: the evolving view of the microtubule-associated protein tau in neurodegenerative diseases. Clin Neuropathol 26:43–58
Lelovas PP, Xanthos TT, Thoma SE, Lyritis GP, Dontas IA (2008) The laboratory rat as an animal model for osteoporosis research. Comp Med 58:424–430
Li Y, Wang J, Sheng JG, Liu L, Barger SW, Jones RA, Van Eldik LJ, Mrak RE, Griffin WS (1998) S100 beta increases levels of beta-amyloid precursor protein and its encoding mRNA in rat neuronal cultures. J Neurochem 71:1421–1428
Lü L, Li J, Yew DT, Rudd JA, Mak YT (2008) Oxidative stress on the astrocytes in culture derived from a senescence accelerated mouse strain. Neurochem Int 52:282–289. doi:10.1016/j.neuint.2007.06.016
Luo Y, Hawver DB, Iwasaki K, Sunderland T, Roth GS, Wolozin B (1997) Physiological levels of beta-amyloid peptide stimulate protein kinase C in PC12 cells. Brain Res 769:287–295. doi:10.1016/S0006-8993(97)00718-X
Mak YT, Chan WY, Lam WP, Yew DT (2006) Immunohistological evidences of Ginkgo biloba extract altering Bax to Bcl-2 expression ratio in the hippocampus and motor cortex of senescence accelerated mice. Microsc Res Tech 69:601–605. doi:10.1002/jemt.20322
Marshak DR (1990) S100 beta as a neurotrophic factor. Prog Brain Res 86:169–181. doi:10.1016/S0079-6123(08)63175-1
Matsunaga W, Shirokawa T, Isobe K (2003) Specific uptake of Abeta1–40 in rat brain occurs in astrocyte, but not in microglia. Neurosci Lett 342:129–131. doi:10.1016/S0304-3940(03)00240-4
Miyazaki H, Okuma Y, Nomura J, Nagashima K, Nomura Y (2003) Age-related alterations in the expression of glial cell line-derived neurotrophic factor in the senescence-accelerated mouse brain. J Pharmacol Sci 92:28–34. doi:10.1254/jphs.92.28
Monnerie H, Esquenazi S, Shashidhara S, Le Roux PD (2005) Beta-amyloid-induced reactive astrocytes display altered ability to support dendrite and axon growth from mouse cerebral cortical neurons in vitro. Neurol Res 27:525–532. doi:10.1179/016164105X40020
Nguyen PK, Smith AL, Reynolds KJ (2008) A literature review of different pressure ulcer models from 1942–2005 and the development of an ideal animal model. Australas Phys Eng Sci Med 31:223–225
Nishikawa T, Takahashi JA, Fujibayashi Y, Fujisawa H, Zhu B, Nishimura Y, Ohnishi K, Higuchi K, Hashimoto N, Hosokawa M (1998) An early stage mechanism of the age-associated mitochondrial dysfunction in the brain of SAMP8 mice; an age-associated neurodegeneration animal model. Neurosci Lett 254:69–72. doi:10.1016/S0304-3940(98)00646-6
Peña LA, Brecher CW, Marshak DR (1995) beta-Amyloid regulates gene expression of glial trophic substance S100 beta in C6 glioma and primary astrocyte cultures. Brain Res Mol Brain Res 34:118–126. doi:10.1016/0169-328X(95)00145-I
Pertusa M, Garcia-Matas S, Rodriguez-Farre E, Sanfeliu C, Cristofol R (2007) Astrocytes aged in vitro show a decreased neuroprotective capacity. J Neurochem 101:794–805. doi:10.1111/j.1471-4159.2006.04369.x
Poon HF, Castegna A, Farr SA, Thongboonkerd V, Lynn BC, Banks WA, Morley JE, Klein JB, Butterfield DA (2004) Quantitative proteomics analysis of specific protein expression and oxidative modification in aged senescence-accelerated-prone 8 mice brain. Neuroscience 126:915–926. doi:10.1016/j.neuroscience.2004.04.046
Praticò D (2008) Oxidative stress hypothesis in Alzheimer’s disease: a reappraisal. Trends Pharmacol Sci 29:609–615. doi:10.1016/j.tips.2008.09.001
Radde R, Duma C, Goedert M, Jucker M (2008) The value of incomplete mouse models of Alzheimer’s disease. Eur J Nucl Med Mol Imaging 35(Suppl 1):S70–S74. doi:10.1007/s00259-007-0704-y
Rall DP (1995) Can laboratory animal carcinogenicity studies predict cancer in exposed children? Environ Health Perspect 103(Suppl 6):173–175. doi:10.2307/3432370
Robinson MK, Cohen C, e Ade B, Ponec M, Whittle E, Fentem JH (2002) Non-animal testing strategies for assessment of the skin corrosion and skin irritation potential of ingredients and finished products. Food Chem Toxicol 40:573–592. doi:10.1016/S0278-6915(02)00005-4
Salinero O, Moreno-Flores MT, Ceballos ML, Wandosell F (1997) beta-Amyloid peptide induced cytoskeletal reorganization in cultured astrocytes. J Neurosci Res 47:216–223. doi:10.1002/(SICI)1097-4547(19970115)47:2<216::AID-JNR10>3.0.CO;2-0
Sánchez-Alvarez R, Tabernero A, Medina JM (2004) Endothelin-1 stimulates the translocation and upregulation of both glucose transporter and hexokinase in astrocytes: relationship with gap junctional communication. J Neurochem 89:703–714. doi:10.1046/j.1471-4159.2004.02398.x
Selkoe DJ, Yamazaki T, Citron M, Podlisny MB, Koo EH, Teplow DB, Haass C (1996) The role of APP processing and trafficking pathways in the formation of amyloid beta-protein. Ann N Y Acad Sci 777:57–64. doi:10.1111/j.1749-6632.1996.tb34401.x
Sjögren M, Davidsson P, Gottfries J, Vanderstichele H, Edman A, Vanmechelen E, Wallin A, Blennow K (2001) The cerebrospinal fluid levels of Tau, growth-associated protein-43 and soluble amyloid precursor protein correlate in Alzheimer’s disease, reflecting a common pathophysiological process. Dement Geriatr Cogn Disord 12:257–264. doi:10.1159/000051268
Smith MA, Siedlak SL, Richey PL, Mulvihill P, Ghiso J, Frangione B, Tagliavini F, Giaccone G, Bugiani O, Praprotnik D, Kalaria RN, Perry G (1995) Tau protein directly interacts with the amyloid beta-protein precursor: implications for Alzheimer’s disease. Nat Med 1:365–369. doi:10.1038/nm0495-365
Takeda T, Hosokawa M, Higuchi K (1991) Senescence-accelerated mouse (SAM): a novel murine model of accelerated senescence. J Am Geriatr Soc 39:911–919
Takuma K, Baba A, Matsuda T (2004) Astrocyte apoptosis: implications for neuroprotection. Prog Neurobiol 72:111–127. doi:10.1016/j.pneurobio.2004.02.001
Tiu SC, Chan WY, Heizmann CW, Schäfer BW, Shu SY, Yew DT (2000) Differential expression of S100B and S100A6(1) in the human fetal and aged cerebral cortex. Brain Res Dev Brain Res 119:159–168. doi:10.1016/S0165-3806(99)00151-0
Wagner KU (2004) Models of breast cancer: quo vadis, animal modeling? Breast Cancer Res 6:31–38. doi:10.1186/bcr723
Wai MS, Liang Y, Shi C, Cho EY, Kung HF, Yew DT (2008) Co-localization of hyperphosphorylated tau and caspases in the brainstem of Alzheimer’s disease patients. Biogerontology. doi:10.1007/s10522-008-9189-8
Wilson JE (2003) Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J Exp Biol 206:2049–2057. doi:10.1242/jeb.00241
Wood CE, Usborne AL, Starost MF, Tarara RP, Hill LR, Wilkinson LM, Geisinger KR, Feiste EA, Cline JM (2006) Hyperplastic and neoplastic lesions of the mammary gland in macaques. Vet Pathol 43:471–483. doi:10.1354/vp.43-4-471
Wu Y, Zhang AQ, Yew DT (2005) Age related changes of various markers of astrocytes in senescence-accelerated mice hippocampus. Neurochem Int 46:565–574. doi:10.1016/j.neuint.2005.01.002
Wyss-Coray T, Loike JD, Brionne TC, Lu E, Anankov R, Yan F, Silverstein SC, Husemann J (2003) Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med 9:453–457. doi:10.1038/nm838
Xu K, Malouf AT, Messing A, Silver J (1999) Glial fibrillary acidic protein is necessary for mature astrocytes to react to beta-amyloid. Glia 25:390–403. doi:10.1002/(SICI)1098-1136(19990215)25:4<390::AID-GLIA8>3.0.CO;2-7
Yew DT, Ping Li W, Liu WK (2004) Fas and activated caspase 8 in normal, Alzheimer and multiple infarct brains. Neurosci Lett 367:113–117. doi:10.1016/j.neulet.2004.05.091
Zhou S, Kestell P, Paxton JW (2002) Predicting pharmacokinetics and drug interactions in patients from in vitro and in vivo models: the experience with 5, 6-dimethylxanthenone-4-acetic acid (DMXAA), an anti-cancer drug eliminated mainly by conjugation. Drug Metab Rev 34:751–790. doi:10.1081/DMR-120015693
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lü, L., Mak, Y.T., Fang, M. et al. The difference in gliosis induced by β-amyloid and Tau treatments in astrocyte cultures derived from senescence accelerated and normal mouse strains. Biogerontology 10, 695–710 (2009). https://doi.org/10.1007/s10522-009-9217-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10522-009-9217-3