Peripheral blood mononuclear cell infiltration and neuroinflammation in the HexB-/- mouse model of neurodegeneration

Stephanos Kyrkanides; Ann W. Miller; Jen nie H. Miller; Ross H. Tallents; Sabine M. Brouxhon; Mallory E. Olschowka; M. Kerry O'Banion; John A. Olschowka

doi:10.1016/j.jneuroim.2008.06.024

Peripheral blood mononuclear cell infiltration and neuroinflammation in the HexB^-/- mouse model of neurodegeneration

Stephanos Kyrkanides, Ann W. Miller, Jen nie H. Miller, Ross H. Tallents, Sabine M. Brouxhon, Mallory E. Olschowka, M. Kerry O'Banion, John A. Olschowka

Oral Health Science

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Myeloid-derived immune cells, including microglia, macrophages and monocytes, have been previously implicated in neurodegeneration. We investigated the role of infiltrating peripheral blood mononuclear cells (PBMC) in neuroinflammation and neurodegeneration in the HexB^-/- mouse model of Sandhoff disease. Ablation of the chemokine receptor CCR2 in the HexB^-/- mouse resulted in significant inhibition of PBMC infiltration into the brain, decrease in TNFα and MHC-II mRNA abundance and retardation in clinical disease development. There was no change in the level of GM₂ storage and pro-apoptotic activity or astrocyte activation in HexB^-/-;Ccr2^-/- double knockout mice, which eventually succumbed secondary to GM₂ gangliosidosis.

Original language	English
Pages (from-to)	50-57
Number of pages	8
Journal	Journal of Neuroimmunology
Volume	203
Issue number	1
DOIs	https://doi.org/10.1016/j.jneuroim.2008.06.024
State	Published - Oct 15 2008

Funding

Funders	Funder number
National Institute of Neurological Disorders and Stroke	R01NS048339

Keywords

CCR2
Chemokine receptors
Microglia
Neurodegeneration
Neuroinflammation
Peripheral blood
Sandhoff disease

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Neurology
Clinical Neurology

Access to Document

10.1016/j.jneuroim.2008.06.024

Cite this

@article{d4fe691bfe554660b0d2773e63a67a1c,

title = "Peripheral blood mononuclear cell infiltration and neuroinflammation in the HexB-/- mouse model of neurodegeneration",

abstract = "Myeloid-derived immune cells, including microglia, macrophages and monocytes, have been previously implicated in neurodegeneration. We investigated the role of infiltrating peripheral blood mononuclear cells (PBMC) in neuroinflammation and neurodegeneration in the HexB-/- mouse model of Sandhoff disease. Ablation of the chemokine receptor CCR2 in the HexB-/- mouse resulted in significant inhibition of PBMC infiltration into the brain, decrease in TNFα and MHC-II mRNA abundance and retardation in clinical disease development. There was no change in the level of GM2 storage and pro-apoptotic activity or astrocyte activation in HexB-/-;Ccr2-/- double knockout mice, which eventually succumbed secondary to GM2 gangliosidosis.",

keywords = "CCR2, Chemokine receptors, Microglia, Neurodegeneration, Neuroinflammation, Peripheral blood, Sandhoff disease",

author = "Stephanos Kyrkanides and Miller, {Ann W.} and Miller, {Jen nie H.} and Tallents, {Ross H.} and Brouxhon, {Sabine M.} and Olschowka, {Mallory E.} and O'Banion, {M. Kerry} and Olschowka, {John A.}",

year = "2008",

month = oct,

day = "15",

doi = "10.1016/j.jneuroim.2008.06.024",

language = "English",

volume = "203",

pages = "50--57",

number = "1",

}

TY - JOUR

T1 - Peripheral blood mononuclear cell infiltration and neuroinflammation in the HexB-/- mouse model of neurodegeneration

AU - Kyrkanides, Stephanos

AU - Miller, Ann W.

AU - Miller, Jen nie H.

AU - Tallents, Ross H.

AU - Brouxhon, Sabine M.

AU - Olschowka, Mallory E.

AU - O'Banion, M. Kerry

AU - Olschowka, John A.

PY - 2008/10/15

Y1 - 2008/10/15

N2 - Myeloid-derived immune cells, including microglia, macrophages and monocytes, have been previously implicated in neurodegeneration. We investigated the role of infiltrating peripheral blood mononuclear cells (PBMC) in neuroinflammation and neurodegeneration in the HexB-/- mouse model of Sandhoff disease. Ablation of the chemokine receptor CCR2 in the HexB-/- mouse resulted in significant inhibition of PBMC infiltration into the brain, decrease in TNFα and MHC-II mRNA abundance and retardation in clinical disease development. There was no change in the level of GM2 storage and pro-apoptotic activity or astrocyte activation in HexB-/-;Ccr2-/- double knockout mice, which eventually succumbed secondary to GM2 gangliosidosis.

AB - Myeloid-derived immune cells, including microglia, macrophages and monocytes, have been previously implicated in neurodegeneration. We investigated the role of infiltrating peripheral blood mononuclear cells (PBMC) in neuroinflammation and neurodegeneration in the HexB-/- mouse model of Sandhoff disease. Ablation of the chemokine receptor CCR2 in the HexB-/- mouse resulted in significant inhibition of PBMC infiltration into the brain, decrease in TNFα and MHC-II mRNA abundance and retardation in clinical disease development. There was no change in the level of GM2 storage and pro-apoptotic activity or astrocyte activation in HexB-/-;Ccr2-/- double knockout mice, which eventually succumbed secondary to GM2 gangliosidosis.

KW - CCR2

KW - Chemokine receptors

KW - Microglia

KW - Neurodegeneration

KW - Neuroinflammation

KW - Peripheral blood

KW - Sandhoff disease

UR - http://www.scopus.com/inward/record.url?scp=52949130599&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=52949130599&partnerID=8YFLogxK

U2 - 10.1016/j.jneuroim.2008.06.024

DO - 10.1016/j.jneuroim.2008.06.024

M3 - Article

C2 - 18657867

AN - SCOPUS:52949130599

SN - 0165-5728

VL - 203

SP - 50

EP - 57

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

IS - 1

ER -