Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer's disease

GLIA - Tập 58 Số 7 - Trang 831-838 - 2010
Markel Olabarria1, Harun N. Noristani, Alexei Verkhratsky, José J. Rodrı́guez
1Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom

Tóm tắt

AbstractAstrocytes are fundamental for brain homeostasis and are at the fulcrum of neurological diseases including Alzheimer's disease (AD). Here, we monitored changes in astroglia morphology throughout the age‐dependent progression of AD. We used an immunohistochemical approach that allows us to determine the domain of glial cytoskeleton, by measuring the surface, volume, and the relationship between astrocytes and neuritic plaques. We investigated astroglia in the hippocampus of a triple transgenic mouse model of AD (3xTg‐AD) that mimics the progression of the human disease. The numerical density of astrocytes is affected neither by AD nor by age. We found reduction of surface and volume of GFAP profiles from early ages (6 months; 43.84 and 52.76%, respectively), persisting at 12 (40.73 and 45.39%) and 18 months (64.80 and 71.95%) in the dentate gyrus (DG) of 3xTg‐AD, whereas in CA1 it appears at 18 months (29.42 and 32.74%). This cytoskeleton atrophy is accompanied by a significant reduction of glial somata volume in DG at 12 and 18 months (40.46 and 75.55%, respectively), whereas in CA1 it is significant at 18 months (42.81%). However, while astroglial atrophy appears as a generalized process, astrocytes surrounding plaques are clearly hypertrophic as revealed by increased surface (48.06%; 66.66%), and volume (57.10%; 71.06%) of GFAP profiles in DG and CA1, respectively, at 18 months. We suggest differential effects of AD on astroglial populations depending on their association with plaques accounting for the progressive disruption of neural networks connectivity and neurotransmitters imbalance which underlie mnesic and cognitive impairments observed in AD. © 2010 Wiley‐Liss, Inc.

Từ khóa


Tài liệu tham khảo

10.1038/nrn1824

10.1523/JNEUROSCI.23-12-05088.2003

10.1523/JNEUROSCI.4042-03.2004

Alzheimer A, 1907, Über eine eigenartige Erkrankung der Hirnrinde, Allg Z Psychiat Psych‐Gericht Med, 64, 146

Alzheimer A, 1910, Histologische und histopathologische Arbeiten über die Grosshirnrinde mit besonderer Berücksichtigung der pathologischen Anatomie der Geisteskrankheiten, 401

10.1007/s11064-007-9335-8

10.1007/PL00014168

10.1093/brain/awh250

10.1002/glia.20642

10.1002/jnr.21113

10.1016/S0301-0082(00)00067-8

10.1016/S0301-0082(99)00060-X

10.1023/A:1007677003387

10.1038/sj.cdd.4402144

10.1016/j.neuroscience.2008.10.018

10.1016/j.molmed.2006.12.005

10.1016/0304-3940(96)12592-1

10.1152/physrev.00049.2005

10.1016/j.neuint.2009.02.020

10.1016/j.neuint.2003.08.015

10.1007/s00424-007-0207-5

10.3233/JAD-2004-6606

10.1016/j.neuroscience.2004.06.008

Kraepelin E, 1919, Dementia praecox and paraphrenia (translated by R. Mary Barclay), 328

10.1126/science.1169096

10.1016/S0006-8993(03)02361-8

10.1016/j.neurobiolaging.2004.01.007

10.1002/glia.20205

10.1016/j.tins.2003.08.008

10.1523/JNEUROSCI.4707-08.2009

10.1016/j.tins.2006.08.004

10.1016/j.neurobiolaging.2003.08.012

10.1016/S0896-6273(03)00434-3

Paxinos G, 2004, The mouse Brain in Stereotaxic Coordinates

10.1016/j.tins.2009.05.001

10.1016/S0920-9964(02)00339-0

10.1371/journal.pone.0002935

10.1097/WNR.0b013e32832be77d

10.1038/cdd.2008.172

10.1038/cdd.2008.99

10.1016/j.brainresbull.2009.07.012

10.1212/01.wnl.0000260698.46517.8f

10.1038/nrn1870

10.1152/physrev.2001.81.2.741

10.1038/sj.npp.1300525

10.1016/j.neuroscience.2004.09.053

Simpson JE, 2008, Astrocyte phenotype in relation to Alzheimer‐type pathology in the ageing brain, Neurobiol Aging

10.1093/jnen/59.12.1118

10.1007/s00424-006-0099-9

10.1111/j.1748-1716.2008.01926.x

10.1038/nrn1722

Wang DD, 2008, The astrocyte odyssey, Prog Neurobiol, 86, 342

10.1073/pnas.0602841103

10.1016/S0896-6273(00)80115-4

Thông tin
Thông tin xuất bản

GLIA

Tập 58 Số 7

831-838

Thông tin tác giả