Concomitant Astrocytic Cytoskeletal Atrophy and Glutamine Synthetase Decrease during the progression of Alzheimer’s disease.

CY. Yeh; M. Olabarria; H. Noristani; A. Verkhratsky; J.J. Rodríguez

Concomitant Astrocytic Cytoskeletal Atrophy and Glutamine Synthetase Decrease during the progression of Alzheimer’s disease.

CY. Yeh, M. Olabarria, H. Noristani, A. Verkhratsky, J.J. Rodríguez

The University of Manchester

Research output: Contribution to conference › Poster

Abstract

Background:Astrocytes, the most numerous cells of the brain, are fundamental for brain homeostasis and are the fulcrum of neurological diseases including Alzheimer's disease (AD). Although extensive literature points towards a hypertrophic reaction of astrocytes during AD, their role remains unknown.Methods:We study the hippocampal astrocytic changes through the progression of AD, using an immunohistochemical approach. This allowed us to study the glial cytoskeleton, by measuring the surface, volume and the relationship between astrocytes and plaques, using a triple transgenic mouse model of AD (3xTg-AD) that mimics the temporal evolution of the human disease.Results:We found a reduction in surface and volume of GFAP from early ages (6 months), being significant at 12 and 18 months in the dentate gyrus (DG) of 3xTg-AD; whilst in CA1 appears at 18 months (>40% reduction). These changes are accompanied by a significant reduction of glial somata volume in DG at 12 and 18 months, whereas in CA1 is significant at 18 months. Whilst astroglial atrophy is a generalised process, astrocytes around plaques are hypertrophic as revealed by an increased surface and volume of GFAP profiles in DG and CA1 respectively at 18 months (>50%). GFAP positive astrocytic numerical density was not affected neither by AD nor by age. However, a decrease in the density of glutamine synthetase expressing astrocytes is also observed in 3xTg-AD, indicating an alteration of gliotransmition.Conclusions:Our results suggest differential effects of AD on astroglial populations depending on their association with plaques, as well as an alteration in glutamatergic transmission throughout the progression of the disease, which will account for the progressive glial and neuronal alterations in synaptic connectivity that appears in AD and reinforce the excitotoxicity mechanism of AD that is responsible of the observed mnesic and cognitive impairments.

Original language	English
Publication status	Published - 11 Jul 2010
Event	Alzheimer's Association International Conference on Alzheimer’s Disease - Honolulu, Hawaii, USA Duration: 10 Jul 2010 → 15 Jul 2010

Conference

Conference	Alzheimer's Association International Conference on Alzheimer’s Disease
City	Honolulu, Hawaii, USA
Period	10/07/10 → 15/07/10

Cite this

@conference{b73c23d8cfeb444faeb14ae373a2b5e3,

title = "Concomitant Astrocytic Cytoskeletal Atrophy and Glutamine Synthetase Decrease during the progression of Alzheimer{\textquoteright}s disease.",

abstract = "Background:Astrocytes, the most numerous cells of the brain, are fundamental for brain homeostasis and are the fulcrum of neurological diseases including Alzheimer's disease (AD). Although extensive literature points towards a hypertrophic reaction of astrocytes during AD, their role remains unknown.Methods:We study the hippocampal astrocytic changes through the progression of AD, using an immunohistochemical approach. This allowed us to study the glial cytoskeleton, by measuring the surface, volume and the relationship between astrocytes and plaques, using a triple transgenic mouse model of AD (3xTg-AD) that mimics the temporal evolution of the human disease.Results:We found a reduction in surface and volume of GFAP from early ages (6 months), being significant at 12 and 18 months in the dentate gyrus (DG) of 3xTg-AD; whilst in CA1 appears at 18 months (>40% reduction). These changes are accompanied by a significant reduction of glial somata volume in DG at 12 and 18 months, whereas in CA1 is significant at 18 months. Whilst astroglial atrophy is a generalised process, astrocytes around plaques are hypertrophic as revealed by an increased surface and volume of GFAP profiles in DG and CA1 respectively at 18 months (>50%). GFAP positive astrocytic numerical density was not affected neither by AD nor by age. However, a decrease in the density of glutamine synthetase expressing astrocytes is also observed in 3xTg-AD, indicating an alteration of gliotransmition.Conclusions:Our results suggest differential effects of AD on astroglial populations depending on their association with plaques, as well as an alteration in glutamatergic transmission throughout the progression of the disease, which will account for the progressive glial and neuronal alterations in synaptic connectivity that appears in AD and reinforce the excitotoxicity mechanism of AD that is responsible of the observed mnesic and cognitive impairments.",

author = "CY. Yeh and M. Olabarria and H. Noristani and A. Verkhratsky and J.J. Rodr{\'i}guez",

year = "2010",

month = jul,

day = "11",

language = "English",

note = "Alzheimer's Association International Conference on Alzheimer{\textquoteright}s Disease ; Conference date: 10-07-2010 Through 15-07-2010",

}

TY - CONF

T1 - Concomitant Astrocytic Cytoskeletal Atrophy and Glutamine Synthetase Decrease during the progression of Alzheimer’s disease.

AU - Yeh, CY.

AU - Olabarria, M.

AU - Noristani, H.

AU - Verkhratsky, A.

AU - Rodríguez, J.J.

PY - 2010/7/11

Y1 - 2010/7/11

N2 - Background:Astrocytes, the most numerous cells of the brain, are fundamental for brain homeostasis and are the fulcrum of neurological diseases including Alzheimer's disease (AD). Although extensive literature points towards a hypertrophic reaction of astrocytes during AD, their role remains unknown.Methods:We study the hippocampal astrocytic changes through the progression of AD, using an immunohistochemical approach. This allowed us to study the glial cytoskeleton, by measuring the surface, volume and the relationship between astrocytes and plaques, using a triple transgenic mouse model of AD (3xTg-AD) that mimics the temporal evolution of the human disease.Results:We found a reduction in surface and volume of GFAP from early ages (6 months), being significant at 12 and 18 months in the dentate gyrus (DG) of 3xTg-AD; whilst in CA1 appears at 18 months (>40% reduction). These changes are accompanied by a significant reduction of glial somata volume in DG at 12 and 18 months, whereas in CA1 is significant at 18 months. Whilst astroglial atrophy is a generalised process, astrocytes around plaques are hypertrophic as revealed by an increased surface and volume of GFAP profiles in DG and CA1 respectively at 18 months (>50%). GFAP positive astrocytic numerical density was not affected neither by AD nor by age. However, a decrease in the density of glutamine synthetase expressing astrocytes is also observed in 3xTg-AD, indicating an alteration of gliotransmition.Conclusions:Our results suggest differential effects of AD on astroglial populations depending on their association with plaques, as well as an alteration in glutamatergic transmission throughout the progression of the disease, which will account for the progressive glial and neuronal alterations in synaptic connectivity that appears in AD and reinforce the excitotoxicity mechanism of AD that is responsible of the observed mnesic and cognitive impairments.

AB - Background:Astrocytes, the most numerous cells of the brain, are fundamental for brain homeostasis and are the fulcrum of neurological diseases including Alzheimer's disease (AD). Although extensive literature points towards a hypertrophic reaction of astrocytes during AD, their role remains unknown.Methods:We study the hippocampal astrocytic changes through the progression of AD, using an immunohistochemical approach. This allowed us to study the glial cytoskeleton, by measuring the surface, volume and the relationship between astrocytes and plaques, using a triple transgenic mouse model of AD (3xTg-AD) that mimics the temporal evolution of the human disease.Results:We found a reduction in surface and volume of GFAP from early ages (6 months), being significant at 12 and 18 months in the dentate gyrus (DG) of 3xTg-AD; whilst in CA1 appears at 18 months (>40% reduction). These changes are accompanied by a significant reduction of glial somata volume in DG at 12 and 18 months, whereas in CA1 is significant at 18 months. Whilst astroglial atrophy is a generalised process, astrocytes around plaques are hypertrophic as revealed by an increased surface and volume of GFAP profiles in DG and CA1 respectively at 18 months (>50%). GFAP positive astrocytic numerical density was not affected neither by AD nor by age. However, a decrease in the density of glutamine synthetase expressing astrocytes is also observed in 3xTg-AD, indicating an alteration of gliotransmition.Conclusions:Our results suggest differential effects of AD on astroglial populations depending on their association with plaques, as well as an alteration in glutamatergic transmission throughout the progression of the disease, which will account for the progressive glial and neuronal alterations in synaptic connectivity that appears in AD and reinforce the excitotoxicity mechanism of AD that is responsible of the observed mnesic and cognitive impairments.

M3 - Poster

T2 - Alzheimer's Association International Conference on Alzheimer’s Disease

Y2 - 10 July 2010 through 15 July 2010

ER -

Concomitant Astrocytic Cytoskeletal Atrophy and Glutamine Synthetase Decrease during the progression of Alzheimer’s disease.

Abstract

Conference

Fingerprint

Cite this