Aging-Related Neurostructural, Neuropathological, and Behavioral Changes Associated with Herpes Simplex Virus Type 1 Brain Infection in Mice

被引:20
作者
Guzman-Sanchez, Fernando [2 ,3 ]
Valdivieso, Fernando [2 ,3 ]
Burgos, Javier S. [1 ]
机构
[1] Neuron Bio, BioPharma Div, Granada 18100, Spain
[2] Univ Autonoma Madrid, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, Madrid, Spain
[3] Consejo Super Invest Cient CBM UAM CSIC, Madrid, Spain
关键词
Aging; apolipoprotein E; brain; HSV-1; infection; gender; mouse; MRI; APOLIPOPROTEIN-E GENOTYPE; ALZHEIMERS-DISEASE; VERTICAL TRANSMISSION; AGENTS CONTRIBUTE; NERVOUS-SYSTEM; E GENE; SPECTROSCOPY; PATHOGENESIS; RECOGNITION; PROGRESSION;
D O I
10.3233/JAD-2012-120070
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
To date, the main advances in understanding Alzheimer's disease (AD) have revolved around the genetic variants associated with the familial form of the disease, yet the majority of cases are sporadic. The main risk factor for AD is aging, followed by production of the E4 isoform of apolipoprotein E (APOE). Female gender also increases the risk of developing AD. Herpes simplex virus type 1 (HSV-1) has been epidemiologically and experimentally associated with AD, although no studies on its effects over aging have been undertaken. To assess the potential aging-related consequences of HSV-1 brain infection, 2 month-old wild-type and apoE-deficient mice were infected with the virus, and over the next 16 months analyses made of cerebral viral load, neuropathological, morphological, and metabolic changes in the brain, and cognitive performance. Viral load in the central nervous system (CNS) increased with age. The viral load in the brains of aged apoE+/+ female mice was 43 times that seen in apoE-/- male mice. No MRI-detectable morphological differences nor any clear neuropathological differences were seen between 18 month-old infected and mock-infected mice, although differences were seen in younger animals. Neuroinfection was associated with memory deficit and a reduction in metabolic indicators of CNS health.
引用
收藏
页码:779 / 790
页数:12
相关论文
共 53 条
  • [1] Inflammation and Alzheimer's disease
    Akiyama, H
    Barger, S
    Barnum, S
    Bradt, B
    Bauer, J
    Cole, GM
    Cooper, NR
    Eikelenboom, P
    Emmerling, M
    Fiebich, BL
    Finch, CE
    Frautschy, S
    Griffin, WST
    Hampel, H
    Hull, M
    Landreth, G
    Lue, LF
    Mrak, R
    Mackenzie, IR
    McGeer, PL
    O'Banion, MK
    Pachter, J
    Pasinetti, G
    Plata-Salaman, C
    Rogers, J
    Rydel, R
    Shen, Y
    Streit, W
    Strohmeyer, R
    Tooyoma, I
    Van Muiswinkel, FL
    Veerhuis, R
    Walker, D
    Webster, S
    Wegrzyniak, B
    Wenk, G
    Wyss-Coray, T
    [J]. NEUROBIOLOGY OF AGING, 2000, 21 (03) : 383 - 421
  • [2] HERPESVIRUS IN THE HIPPOCAMPUS AS A CAUSE OF ALZHEIMERS-DISEASE
    BALL, MJ
    [J]. ARCHIVES OF NEUROLOGY, 1986, 43 (04) : 313 - 313
  • [3] HYPOTHESIS - LIMBIC PREDILECTION IN ALZHEIMER DEMENTIA - IS REACTIVATED HERPESVIRUS INVOLVED
    BALL, MJ
    [J]. CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES, 1982, 9 (03) : 303 - 306
  • [4] Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database
    Bertram, Lars
    McQueen, Matthew B.
    Mullin, Kristina
    Blacker, Deborah
    Tanzi, Rudolph E.
    [J]. NATURE GENETICS, 2007, 39 (01) : 17 - 23
  • [5] Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study 'recognition memory'
    Bevins, Rick A.
    Besheer, Joyce
    [J]. NATURE PROTOCOLS, 2006, 1 (03) : 1306 - 1311
  • [6] Effect of human apolipoprotein E genotype on the pathogenesis of experimental ocular HSV-1
    Bhattacharjee, Partha S.
    Neumann, Donna M.
    Foster, Timothy P.
    Bouhanik, Saadallah
    Clement, Christian
    Vinay, Dass
    Thompson, Hilary W.
    Hill, James M.
    [J]. EXPERIMENTAL EYE RESEARCH, 2008, 87 (02) : 122 - 130
  • [7] Alzheimer's disease
    Scheltens, Philip
    De Strooper, Bart
    Kivipelto, Miia
    Holstege, Henne
    Chetelat, Gael
    Teunissen, Charlotte E.
    Cummings, Jeffrey
    van der Flier, Wiesje M.
    [J]. LANCET, 2021, 397 (10284) : 1577 - 1590
  • [8] Apolipoprotein E genotype influences vertical transmission of herpes simplex virus type 1 in a gender specific manner
    Burgos, Javier S.
    Ramirez, Carlos
    Sastre, Isabel
    Valdivieso, Fernando
    [J]. AGING CELL, 2007, 6 (06) : 841 - 842
  • [9] Effect of apolipoprotein E on the cerebral load of latent herpes simplex virus type 1 DNA
    Burgos, Javier S.
    Ramirez, Carlos
    Sastre, Isabel
    Valdivieso, Fernando
    [J]. JOURNAL OF VIROLOGY, 2006, 80 (11) : 5383 - 5387
  • [10] Hematogenous vertical transmission of herpes simplex virus type 1 in mice
    Burgos, JS
    Ramirez, C
    Guzman-Sanchez, F
    Alfaro, JM
    Sastre, I
    Valdivieso, F
    [J]. JOURNAL OF VIROLOGY, 2006, 80 (06) : 2823 - 2831