Lab Anim Res.  2011 Sep;27(3):181-187. 10.5625/lar.2011.27.3.181.

Microglia in the normally aged hippocampus

Affiliations
  • 1Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon, Korea.
  • 2Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Korea. mhwon@kangwon.ac.kr

Abstract

The hippocampus plays important roles in the regulation and combination of short and long term memory and spatial navigation with other brain centers. Aging is accompanied by a functional decline of the hippocampus and degenerative disease. Microglia are major immune cells in the central nervous system and response to degenerative changes in the aged brain. In this respect, functional and morphological changes of the hippocampus have been closely related to microglial changes during normal aging with or without disease. Therefore, in this review, we discuss morphological and functional changes of the hippocampus and microglia in the aging brain.

Keyword

Aging; brain; memory; immune cells

MeSH Terms

Aged
Aging
Brain
Central Nervous System
Hippocampus
Humans
Memory
Microglia

Reference

1. Hamill RW, Caine E, Eskin T, Lapham L, Shoulson I, McNeill TH. Neurodegenerative disorders and aging. Alzheimer's disease and Parkinson's disease--common ground. Ann N Y Acad Sci. 1988; 515:411–420. PMID: 3284427.
2. McGeer PL, McGeer EG. Inflammation and the degenerative diseases of aging. Ann N Y Acad Sci. 2004; 1035:104–116. PMID: 15681803.
Article
3. Vanguilder HD, Freeman WM. The hippocampal neuroproteome with aging and cognitive decline: past progress and future directions. Front Aging Neurosci. 2011; 3:8. PMID: 21647399.
Article
4. Sweatt JD. Hippocampal function in cognition. Psychopharmacology (Berl). 2004; 174(1):99–110. PMID: 15205881.
Article
5. Rasmussen T, Schliemann T, Sorensen JC, Zimmer J, West MJ. Memory impaired aged rats: no loss of principal hippocampal and subicular neurons. Neurobiol Aging. 1996; 17(1):143–147. PMID: 8786797.
Article
6. Burke SN, Barnes CA. Neural plasticity in the ageing brain. Nat Rev Neurosci. 2006; 7(1):30–40. PMID: 16371948.
Article
7. West MJ, Coleman PD, Flood DG, Troncoso JC. Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease. Lancet. 1994; 344(8925):769–772. PMID: 7916070.
Article
8. Lee CH, Yoo KY, Choi JH, Park OK, Hwang IK, Kim SK, Kang IJ, Kim YM, Won MH. Neuronal damage is much delayed and microgliosis is more severe in the aged hippocampus induced by transient cerebral ischemia compared to the adult hippocampus. J Neurol Sci. 2010; 294(1-2):1–6. PMID: 20471038.
Article
9. Sapolsky RM, Krey LC, McEwen BS. Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response. Proc Natl Acad Sci USA. 1984; 81(19):6174–6177. PMID: 6592609.
Article
10. Bobinski M, de Leon MJ, Tarnawski M, Wegiel J, Reisberg B, Miller DC, Wisniewski HM. Neuronal and volume loss in CA1 of the hippocampal formation uniquely predicts duration and severity of Alzheimer disease. Brain Res. 1998; 805(1-2):267–269. PMID: 9733982.
Article
11. Alabarse PV, Hackenhaar FS, Medeiros TM, Mendes MF, Viacava PR, Schuller AK, Salomon TB, Ehrenbrink G, Benfato MS. Oxidative stress in the brain of reproductive male rats during aging. Exp Gerontol. 2011; 46(4):241–248. PMID: 20971183.
Article
12. Tomasi D, Volkow ND. Aging and functional brain networks. Mol Psychiatry. 2011; in press.
Article
13. Perry VH, Nicoll JA, Holmes C. Microglia in neurodegenerative disease. Nat Rev Neurol. 2010; 6(4):193–201. PMID: 20234358.
Article
14. Mrak RE, Griffin WS. Glia and their cytokines in progression of neurodegeneration. Neurobiol Aging. 2005; 26(3):349–354. PMID: 15639313.
Article
15. Lawson LJ, Perry VH, Dri P, Gordon S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience. 1990; 39(1):151–170. PMID: 2089275.
Article
16. Streit WJ. Microglia in the regenerating and degenerating central nervous system. 2002. New York: Springer;p. 315.
17. Dilger RN, Johnson RW. Aging, microglial cell priming, and the discordant central inflammatory response to signals from the peripheral immune system. J Leukoc Biol. 2008; 84(4):932–939. PMID: 18495785.
Article
18. Lister JP, Barnes CA. Neurobiological changes in the hippocampus during normative aging. Arch Neurol. 2009; 66(7):829–833. PMID: 19597084.
Article
19. McEwen BS. Stress and the aging hippocampus. Front Neuroendocrinol. 1999; 20(1):49–70. PMID: 9882536.
Article
20. Luo XG, Ding JQ, Chen SD. Microglia in the aging brain: relevance to neurodegeneration. Mol Neurodegener. 2010; 5:12. PMID: 20334662.
Article
21. Miller DB, O'Callaghan JP. Aging, stress and the hippocampus. Ageing Res Rev. 2005; 4(2):123–140. PMID: 15964248.
Article
22. Gross CG. Brain, vision, memory: tales in the history of neuroscience. 1998. Cambridge: MIT Press;p. 273.
23. Kesner RP, Lee I, Gilbert P. A behavioral assessment of hippocampal function based on a subregional analysis. Rev Neurosci. 2004; 15(5):333–351. PMID: 15575490.
Article
24. Miyashita T, Williams CL. Peripheral arousal-related hormones modulate norepinephrine release in the hippocampus via influences on brainstem nuclei. Behav Brain Res. 2004; 153(1):87–95. PMID: 15219710.
Article
25. Koehl M, Abrous DN. A new chapter in the field of memory: adult hippocampal neurogenesis. Eur J Neurosci. 2011; 33(6):1101–1114. PMID: 21395854.
Article
26. Norman KA. How hippocampus and cortex contribute to recognition memory: revisiting the complementary learning systems model. Hippocampus. 2010; 20(11):1217–1227. PMID: 20857486.
Article
27. Brown MW, Warburton EC, Aggleton JP. Recognition memory: material, processes, and substrates. Hippocampus. 2010; 20(11):1228–1244. PMID: 20848602.
Article
28. Langston RF, Stevenson CH, Wilson CL, Saunders I, Wood ER. The role of hippocampal subregions in memory for stimulus associations. Behav Brain Res. 2010; 215(2):275–291. PMID: 20633579.
Article
29. Niewiadomska G, Baksalerska-Pazera M, Riedel G. The septo-hippocampal system, learning and recovery of function. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33(5):791–805. PMID: 19389457.
Article
30. Shankaranarayana Rao BS, Govindaiah , Laxmi TR, Meti BL, Raju TR. Subicular lesions cause dendritic atrophy in CA1 and CA3 pyramidal neurons of the rat hippocampus. Neuroscience. 2001; 102(2):319–327. PMID: 11166118.
Article
31. Bondareff W. Synaptic atrophy in the senescent hippocampus. Mech Ageing Dev. 1979; 9(1-2):163–171. PMID: 439949.
Article
32. Ball MJ. Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. A quantitative study. Acta Neuropathol. 1977; 37(2):111–118. PMID: 848276.
33. Issa AM, Rowe W, Gauthier S, Meaney MJ. Hypothalamic-pituitary-adrenal activity in aged, cognitively impaired and cognitively unimpaired rats. J Neurosci. 1990; 10(10):3247–3254. PMID: 2170594.
Article
34. Rapp PR, Gallagher M. Preserved neuron number in the hippocampus of aged rats with spatial learning deficits. Proc Natl Acad Sci USA. 1996; 93(18):9926–9930. PMID: 8790433.
Article
35. Hof PR, Glannakopoulos P, Bouras C. The neuropathological changes associated with normal brain aging. Histol Histopathol. 1996; 11(4):1075–1088. PMID: 8930649.
36. West MJ, Gundersen HJ. Unbiased stereological estimation of the number of neurons in the human hippocampus. J Comp Neurol. 1990; 296(1):1–22. PMID: 2358525.
Article
37. Calhoun ME, Kurth D, Phinney AL, Long JM, Hengemihle J, Mouton PR, Ingram DK, Jucker M. Hippocampal neuron and synaptophysin-positive bouton number in aging C57BL/6 mice. Neurobiol Aging. 1998; 19(6):599–606. PMID: 10192220.
Article
38. Keuker JI, Luiten PG, Fuchs E. Preservation of hippocampal neuron numbers in aged rhesus monkeys. Neurobiol Aging. 2003; 24(1):157–165. PMID: 12493561.
Article
39. West MJ. Design-based stereological methods for counting neurons. Prog Brain Res. 2002; 135:43–51. PMID: 12143362.
Article
40. Ziehn MO, Avedisian AA, Tiwari-Woodruff S, Voskuhl RR. Hippocampal CA1 atrophy and synaptic loss during experimental autoimmune encephalomyelitis, EAE. Lab Invest. 2010; 90(5):774–786. PMID: 20157291.
Article
41. Varon D, Loewenstein DA, Potter E, Greig MT, Agron J, Shen Q, Zhao W, Celeste Ramirez M, Santos I, Barker W, Potter H, Duara R. Minimal atrophy of the entorhinal cortex and hippocampus: progression of cognitive impairment. Dement Geriatr Cogn Disord. 2011; 31(4):276–283. PMID: 21494034.
Article
42. Mu Q, Xie J, Wen Z, Weng Y, Shuyun Z. A quantitative MR study of the hippocampal formation, the amygdala, and the temporal horn of the lateral ventricle in healthy subjects 40 to 90 years of age. AJNR AM J Neuroradiol. 1999; 20(2):207–211. PMID: 10094339.
43. Raz N, Ghisletta P, Rodrigue KM, Kennedy KM, Lindenberger U. Trajectories of brain aging in middle-aged and older adults: regional and individual differences. Neuroimage. 2010; 51(2):501–511. PMID: 20298790.
Article
44. Malykhin NV, Bouchard TP, Camicioli R, Coupland NJ. Aging hippocampus and amygdala. Neuroreport. 2008; 19(5):543–547. PMID: 18388735.
Article
45. Pyapali GK, Turner DA. Increased dendritic extent in hippocampal CA1 neurons from aged F344 rats. Neurobiol Aging. 1996; 17(4):601–611. PMID: 8832635.
Article
46. Markham JA, McKian KP, Stroup TS, Juraska JM. Sexually dimorphic aging of dendritic morphology in CA1 of hippocampus. Hippocampus. 2005; 15(1):97–103. PMID: 15390161.
Article
47. Flood DG, Buell SJ, Horwitz GJ, Coleman PD. Dendritic extent in human dentate gyrus granule cells in normal aging and senile dementia. Brain Res. 1987; 402(2):205–216. PMID: 3828793.
Article
48. Curcio CA, Hinds JW. Stability of synaptic density and spine volume in dentate gyrus of aged rats. Neurobiol Aging. 1983; 4(1):77–87. PMID: 6877491.
Article
49. Williams RS, Matthysse S. Age-related changes in Down syndrome brain and the cellular pathology of Alzheimer disease. Prog Brain Res. 1986; 70:49–67. PMID: 2953042.
50. Barnes CA. Normal aging: regionally specific changes in hippocampal synaptic transmission. Trends Neurosci. 1994; 17(1):13–18. PMID: 7511843.
Article
51. Bondareff W, Geinisman Y. Loss of synapses in the dentate gyrus of the senescent rat. Am J Anat. 1976; 145(1):129–136. PMID: 1246966.
Article
52. Barnes CA, Rao G, Houston FP. LTP induction threshold change in old rats at the perforant path--granule cell synapse. Neurobiol Aging. 2000; 21(5):613–620. PMID: 11016529.
Article
53. von Bohlen und Halbach O, Unsicker K. Morphological alterations in the amygdala and hippocampus of mice during ageing. Eur J Neurosci. 2002; 16(12):2434–2440. PMID: 12492438.
54. von Bohlen und Halbach O, Unsicker K. Age-related decline in the tyrosine hydroxylase-immunoreactive innervation of the amygdala and dentate gyrus in mice. Cell Tissue Res. 2003; 311(2):139–143. PMID: 12596034.
Article
55. Nishimura A, Ueda S, Takeuchi Y, Sawada T, Kawata M. Age-related decrease of serotonergic fibres and S-100 beta immunoreactivity in the rat dentate gyrus. Neuroreport. 1995; 6(10):1445–1448. PMID: 7488745.
56. Ypsilanti AR, Girao da Cruz MT, Burgess A, Aubert I. The length of hippocampal cholinergic fibers is reduced in the aging brain. Neurobiol Aging. 2008; 29(11):1666–1679. PMID: 17507114.
Article
57. Sapolsky RM, Krey LC, McEwen BS. Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging. J Neurosci. 1985; 5(5):1222–1227. PMID: 3998818.
Article
58. Landfield PW, Waymire JC, Lynch G. Hippocampal aging and adrenocorticoids: quantitative correlations. Science. 1978; 202(4372):1098–1102. PMID: 715460.
Article
59. Bremner JD, Narayan M. The effects of stress on memory and the hippocampus throughout the life cycle: implications for childhood development and aging. Dev Psychopathol. 1998; 10(4):871–885. PMID: 9886231.
60. Kumar A, Bodhinathan K, Foster TC. Susceptibility to Calcium Dysregulation during Brain Aging. Front Aging Neurosci. 2009; 1:2. doi:10.3389/neuro.24.002.2009. PMID: 20552053.
Article
61. Foster TC, Kumar A. Calcium dysregulation in the aging brain. Neuroscientist. 2002; 8(4):297–301. PMID: 12194497.
Article
62. Disterhoft JF, Kronforst-Collins M, Oh MM, Power JM, Preston AR, Weiss C. Cholinergic facilitation of trace eyeblink conditioning in aging rabbits. Life Sci. 1999; 64(6-7):541–548. PMID: 10069521.
Article
63. Landfield PW, Pitler TA. Prolonged Ca2+-dependent afterhyperpolarizations in hippocampal neurons of aged rats. Science. 1984; 226(4678):1089–1092. PMID: 6494926.
64. Moyer JR Jr, Disterhoft JF. Nimodipine decreases calcium action potentials in rabbit hippocampal CA1 neurons in an age-dependent and concentration-dependent manner. Hippocampus. 1994; 4(1):11–17. PMID: 8061749.
Article
65. Thibault O, Landfield PW. Increase in single L-type calcium channels in hippocampal neurons during aging. Science. 1996; 272(5264):1017–1020. PMID: 8638124.
Article
66. Billard JM. Ageing, hippocampal synaptic activity and magnesium. Magnes Res. 2006; 19(3):199–215. PMID: 17172010.
67. Bardgett ME, Schultheis PJ, McGill DL, Richmond RE, Wagge JR. Magnesium deficiency impairs fear conditioning in mice. Brain Res. 2005; 1038(1):100–106. PMID: 15748878.
Article
68. Slutsky I, Abumaria N, Wu LJ, Huang C, Zhang L, Li B, Zhao X, Govindarajan A, Zhao MG, Zhuo M, Tonegawa S, Liu G. Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010; 65(2):165–177. PMID: 20152124.
Article
69. von Bohlen und Halbach O. Involvement of BDNF in age-dependent alterations in the hippocampus. Front Aging Neurosci. 2010; 2:36. PMID: 20941325.
70. Hayashi M, Mistunaga F, Ohira K, Shimizu K. Changes in BDNF-immunoreactive structures in the hippocampal formation of the aged macaque monkey. Brain Res. 2001; 918(1-2):191–196. PMID: 11684059.
Article
71. Webster MJ, Herman MM, Kleinman JE, Shannon Weickert C. BDNF and trkB mRNA expression in the hippocampus and temporal cortex during the human lifespan. Gene Expr Patterns. 2006; 6(8):941–951. PMID: 16713371.
Article
72. Silhol M, Bonnichon V, Rage F, Tapia-Arancibia L. Age-related changes in brain-derived neurotrophic factor and tyrosine kinase receptor isoforms in the hippocampus and hypothalamus in male rats. Neuroscience. 2005; 132(3):613–624. PMID: 15837123.
Article
73. Gooney M, Messaoudi E, Maher FO, Bramham CR, Lynch MA. BDNF-induced LTP in dentate gyrus is impaired with age: analysis of changes in cell signaling events. Neurobiol Aging. 2004; 25(10):1323–1331. PMID: 15465630.
Article
74. VanGuilder HD, Yan H, Farley JA, Sonntag WE, Freeman WM. Aging alters the expression of neurotransmission-regulating proteins in the hippocampal synaptoproteome. J Neurochem. 2010; 113(6):1577–1588. PMID: 20374424.
Article
75. Freeman WM, VanGuilder HD, Bennett C, Sonntag WE. Cognitive performance and age-related changes in the hippocampal proteome. Neuroscience. 2009; 159(1):183–195. PMID: 19135133.
Article
76. Davis EJ, Foster TD, Thomas WE. Cellular forms and functions of brain microglia. Brain Res Bull. 1994; 34(1):73–78. PMID: 8193937.
Article
77. Perry VH, Andersson PB, Gordon S. Macrophages and inflammation in the central nervous system. Trends Neurosci. 1993; 16(7):268–273. PMID: 7689770.
Article
78. Streit WJ, Graeber MB, Kreutzberg GW. Functional plasticity of microglia: a review. Glia. 1988; 1(5):301–307. PMID: 2976393.
Article
79. Perry VH. The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease. Brain Behav Immun. 2004; 18(5):407–413. PMID: 15265532.
Article
80. Perry VH, Matyszak MK, Fearn S. Altered antigen expression of microglia in the aged rodent CNS. Glia. 1993; 7(1):60–67. PMID: 8423063.
Article
81. Perry VH, Newman TA, Cunningham C. The impact of systemic infection on the progression of neurodegenerative disease. Nat Rev Neurosci. 2003; 4(2):103–112. PMID: 12563281.
Article
82. Choi JH, Lee CH, Hwang IK, Won MH, Seong JK, Yoon YS, Lee HS, Lee IS. Age-related changes in ionized calcium-binding adapter molecule 1 immunoreactivity and protein level in the gerbil hippocampal CA1 region. J Vet Med Sci. 2007; 69(11):1131–1136. PMID: 18057827.
Article
83. Wirenfeldt M, Dalmau I, Finsen B. Estimation of absolute microglial cell numbers in mouse fascia dentata using unbiased and efficient stereological cell counting principles. Glia. 2003; 44(2):129–139. PMID: 14515329.
Article
84. Vanderwolf CH. Hippocampal activity, olfaction, and sniffing: an olfactory input to the dentate gyrus. Brain Res. 1992; 593(2):197–208. PMID: 1450928.
Article
85. Long JM, Kalehua AN, Muth NJ, Hengemihle JM, Jucker M, Calhoun ME, Ingram DK, Mouton PR. Stereological estimation of total microglia number in mouse hippocampus. J Neurosci Methods. 1998; 84(1-2):101–108. PMID: 9821640.
Article
86. Savchenko VL, McKanna JA, Nikonenko IR, Skibo GG. Microglia and astrocytes in the adult rat brain: comparative immunocytochemical analysis demonstrates the efficacy of lipocortin 1 immunoreactivity. Neuroscience. 2000; 96(1):195–203. PMID: 10683423.
Article
87. Imai Y, Ibata I, Ito D, Ohsawa K, Kohsaka S. A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem Biophys Res Commun. 1996; 224(3):855–862. PMID: 8713135.
88. Jinno S, Fleischer F, Eckel S, Schmidt V, Kosaka T. Spatial arrangement of microglia in the mouse hippocampus: a stereological study in comparison with astrocytes. Glia. 2007; 55(13):1334–1347. PMID: 17647290.
Article
89. Long JM, Kalehua AN, Muth NJ, Calhoun ME, Jucker M, Hengemihle JM, Ingram DK, Mouton PR. Stereological analysis of astrocyte and microglia in aging mouse hippocampus. Neurobiol Aging. 1998; 19(5):497–503. PMID: 9880052.
Article
90. Mouton PR, Long JM, Lei DL, Howard V, Jucker M, Calhoun ME, Ingram DK. Age and gender effects on microglia and astrocyte numbers in brains of mice. Brain Res. 2002; 956(1):30–35. PMID: 12426043.
Article
91. Hayakawa N, Kato H, Araki T. Age-related changes of astorocytes, oligodendrocytes and microglia in the mouse hippocampal CA1 sector. Mech Ageing Dev. 2007; 128(4):311–316. PMID: 17350671.
Article
92. Adachi M, Abe M, Sasaki T, Kato H, Kasahara J, Araki T. Role of inducible or neuronal nitric oxide synthase in neurogenesis of the dentate gyrus in aged mice. Metab Brain Dis. 2010; 25(4):419–424. PMID: 21082337.
Article
93. Park JH, Yoo KY, Lee CH, Kim IH, Shin BN, Choi JH, Hwang IK, Won MH. Comparison of glucocorticoid receptor and ionized calcium-binding adapter molecule 1 immunoreactivity in the adult and aged gerbil hippocampus following repeated restraint stress. Neurochem Res. 2011; 36(6):1037–1045. PMID: 21399905.
Article
94. Hwang IK, Lee CH, Li H, Yoo KY, Choi JH, Kim DW, Suh HW, Won MH. Comparison of ionized calcium-binding adapter molecule 1 immunoreactivity of the hippocampal dentate gyrus and CA1 region in adult and aged dogs. Neurochem Res. 2008; 33(7):1309–1315. PMID: 18270819.
Article
95. Nicolle MM, Gonzalez J, Sugaya K, Baskerville KA, Bryan D, Lund K, Gallagher M, McKinney M. Signatures of hippocampal oxidative stress in aged spatial learning-impaired rodents. Neuroscience. 2001; 107(3):415–431. PMID: 11718997.
Article
96. Finch CE. Neurons, glia, and plasticity in normal brain aging. Neurobiol Aging. 2003; 24(Suppl 1):S123–S127. PMID: 12829120.
Article
97. Finch CE. Neurons, glia, and plasticity in normal brain aging. Adv Gerontol. 2002; 10:35–39. PMID: 12577689.
Article
98. Chen J, Buchanan JB, Sparkman NL, Godbout JP, Freund GG, Johnson RW. Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system. Brain Behav Immun. 2008; 22(3):301–311. PMID: 17951027.
Article
99. Sheng JG, Mrak RE, Griffin WS. Enlarged and phagocytic, but not primed, interleukin-1 alpha-immunoreactive microglia increase with age in normal human brain. Acta Neuropathol. 1998; 95(3):229–234. PMID: 9542587.
100. Godbout JP, Chen J, Abraham J, Richwine AF, Berg BM, Kelley KW, Johnson RW. Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system. FASEB J. 2005; 19(10):1329–1331. PMID: 15919760.
101. Sierra A, Gottfried-Blackmore AC, McEwen BS, Bulloch K. Microglia derived from aging mice exhibit an altered inflammatory profile. Glia. 2007; 55(4):412–424. PMID: 17203473.
Article
102. Ye SM, Johnson RW. Increased interleukin-6 expression by microglia from brain of aged mice. J Neuroimmunol. 1999; 93(1-2):139–148. PMID: 10378877.
Article
103. Sparkman NL, Johnson RW. Neuroinflammation associated with aging sensitizes the brain to the effects of infection or stress. Neuroimmunomodulation. 2008; 15(4-6):323–330. PMID: 19047808.
Article
104. Wu Z, Tokuda Y, Zhang XW, Nakanishi H. Age-dependent responses of glial cells and leptomeninges during systemic inflammation. Neurobiol Dis. 2008; 32(3):543–551. PMID: 18848892.
Article
105. Barrientos RM, Higgins EA, Biedenkapp JC, Sprunger DB, Wright-Hardesty KJ, Watkins LR, Rudy JW, Maier SF. Peripheral infection and aging interact to impair hippocampal memory consolidation. Neurobiol Aging. 2006; 27(5):723–732. PMID: 15893410.
Article
106. Wynne AM, Henry CJ, Godbout JP. Immune and behavioral consequences of microglial reactivity in the aged brain. Integr Comp Biol. 2009; 49(3):254–266. PMID: 21665818.
Article
107. Streit WJ, Sammons NW, Kuhns AJ, Sparks DL. Dystrophic microglia in the aging human brain. Glia. 2004; 45(2):208–212. PMID: 14730714.
Article
108. Korotzer AR, Pike CJ, Cotman CW. beta-Amyloid peptides induce degeneration of cultured rat microglia. Brain Res. 1993; 624(1-2):121–125. PMID: 8252383.
109. Streit WJ, Xue QS. Life and death of microglia. J Neuroimmune Pharmacol. 2009; 4(4):371–379. PMID: 19680817.
Article
110. Streit WJ, Braak H, Xue QS, Bechmann I. Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer's disease. Acta Neuropathol. 2009; 118(4):475–485. PMID: 19513731.
Article
111. v Eitzen U, Egensperger R, Kosel S, Grasbon-Frodl EM, Imai Y, Bise K, Kohsaka S, Mehraein P, Graeber MB. Microglia and the development of spongiform change in Creutzfeldt-Jakob disease. J Neuropathol Exp Neurol. 1998; 57(3):246–256. PMID: 9600217.
Article
112. Fendrick SE, Xue QS, Streit WJ. Formation of multinucleated giant cells and microglial degeneration in rats expressing a mutant Cu/Zn superoxide dismutase gene. J Neuroinflammation. 2007; 4:9. PMID: 17328801.
Article
113. Simmons DA, Casale M, Alcon B, Pham N, Narayan N, Lynch G. Ferritin accumulation in dystrophic microglia is an early event in the development of Huntington's disease. Glia. 2007; 55(10):1074–1084. PMID: 17551926.
Article
114. Miller KR, Streit WJ. The effects of aging, injury and disease on microglial function: a case for cellular senescence. Neuron Glia Biol. 2007; 3(3):245–253. PMID: 18634615.
Article
115. Flanary BE, Sammons NW, Nguyen C, Walker D, Streit WJ. Evidence that aging and amyloid promote microglial cell senescence. Rejuvenation Res. 2007; 10(1):61–74. PMID: 17378753.
Article
116. Streit WJ. Microglial senescence: does the brain's immune system have an expiration date? Trends Neurosci. 2006; 29(9):506–510. PMID: 16859761.
Article
117. Flanary B. The role of microglial cellular senescence in the aging and Alzheimer diseased brain. Rejuvenation Res. 2005; 8(2):82–85. PMID: 15929715.
Article
Full Text Links
  • LAR
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr