Amyloid Beta1-42 Induced Glial Activation and Cell Death in Corpus Callosum in Vivo

Abstract

White matter degeneration is a frequent phenomenon found in Alzheimer's disease

(AD) apart from the well-known lesions in certain grey matter areas such as cortex and

hippocampus. However its pathogenesis has not been fully established. Therefore, the aim of

this work was to assess the effects of Aβ 1-42 in rat corpus callosum from 6 hr upto 2 weeks

using immunocytochemistry since amyloid deposits can be found in CC of AD patients.

Administration of 1 nmol of Aβ 1-42 into corpus callosum resulted in considerable damage to

axons, as evidenced by the loss of neurofilament-immunoreactive fibers at time points of 6

hrs and 7 days post-injection. Significant damage was also evident to myelin (using Luxol fast

blue myelin staining) and oligodendrocytes (using CC1 irnmunocytochemistry); in the latter

case marked caspase-3 immunoreactivity was demonstrated in the CC 1-immunoreactive

oligodendrocytes. Additionally, the numbers of GFAP-immunoreactive astrocytes and OX-

42/OX-6-immunoreactive microglia were markedly increased following Aβ 1-42 injection.

These findings suggest that Aβ 1-42 plays an important pathophysiological role in white

matter damage and one possible mechanism of oligodendroglial death is through activation of

caspase-3. This is the first finding on Aβ 1-42-induced toxicity in corpus callosum in vivo

which could provide a potential new model for the study of white matter damage in AD.