Peripheral blood mononuclear cell infiltration and neuroinflammation in the HexB-/- mouse model of neurodegeneration.
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 TNFalpha 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.
Kyrkanides
Stephanos
S
Department of Neurobiology & Anatomy, School of Medicine & Dentistry, University of Rochester Rochester NY 14642, USA. Stephanos_kyrkanides@urmc.rochester.edu
Miller
Ann W
AW
Miller
Jen-Nie H
JN
Tallents
Ross H
RH
Brouxhon
Sabine M
SM
Olschowka
Mallory E
ME
O'Banion
M Kerry
MK
Olschowka
John A
JA
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005678:G(M2) Ganglioside / Q000378:metabolism; D054819:Hexosaminidase B / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology / Q000473:pathology; D009410:Nerve Degeneration / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology; D012497:Sandhoff Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D005678:G(M2) Ganglioside; D054819:Hexosaminidase B