Amyloid beta peptide-induced corpus callosum damage and glial activation in vivo.
The effects of stereotaxic injection of amyloid beta-peptide (Abeta1-42) into rat brain to induce white matter damage have been studied. Administration of 1 nmol Abeta1-42 into corpus callosum resulted in considerable damage to axons as evidenced by the loss of neurofilament-immunoreactive (NF-ir) fibers 6 h and 3 and 7 days post-injection. Significant damage was also evident to myelin (using Luxol fast blue myelin staining) and oligodendrocytes (using CC1 immunocytochemistry); in the latter case marked caspase-3 immunoreactivity was evident in oligodendrocytes. Additionally, the numbers of GFAP-ir astrocytes and OX-42/OX-6-ir microglia were markedly increased following Abeta1-42 injection. These results suggest that Abeta plays an important pathophysiological role in white matter damage and that inflammatory responses may contribute to Abeta-induced demyelination and oligodendrocyte injury in corpus callosum. Loss of function of cells in corpus callosum could provide a potential new model for the study of white matter damage in Alzheimer's disease.
Jantaratnotai
Nattinee
N
Department of Pharmacology, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
Ryu
Jae K
JK
Kim
Seung U
SU
McLarnon
James G
JG
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001369:Axons / Q000187:drug effects / Q000473:pathology; D004396:Coloring Agents; D003337:Corpus Callosum / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology; D007150:Immunohistochemistry; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D008856:Microscopy, Fluorescence; D009186:Myelin Sheath / Q000473:pathology; D009412:Nerve Fibers / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects* / Q000473:pathology; D009836:Oligodendroglia / Q000502:physiology; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques
D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)