Dk. Song et al., BEHAVIORAL AND NEUROPATHOLOGIC CHANGES INDUCED BY CENTRAL INJECTION OF CARBOXYL-TERMINAL FRAGMENT OF BETA-AMYLOID PRECURSOR PROTEIN IN MICE, Journal of neurochemistry, 71(2), 1998, pp. 875-878
Expression of the carboxyl-terminal fragment (CT) of the beta-amyloid
precursor protein (APP) in transgenic animals has been linked with neu
rotoxicity. However, it remains to be clarified whether the neurotoxic
ity is caused by beta-amyloid proteins (A beta s) derived from CT or b
y CT itself. To study the in vivo neurotoxicity of CT, mice were given
a single intracerebroventricular injection of a recombinant 105-amino
acid CT (CT105; 68.5-685 pmol, intracerebroventricularly), and change
s in behavior and in brain histology were examined. Animals given CT10
5 (410 or 685 pmol, intracerebroventricularly) showed a dose-dependent
impairment in the passive avoidance performance, whereas boiled CT105
had no effect. CT105 (685 pmol, intracerebroventricularly) induced re
active gliosis in neocortex and hippocampus and neurodegeneration in n
eocortex. These results indicate that centrally administered CT105 ind
uces behavioral impairment and neuropathologic changes, suggesting a d
irect toxic effect of CT105 per se.