Behavioral and neuropathologic changes induced by central injection of carboxyl-terminal fragment of beta-amyloid precursor protein in mice.
Expression of the carboxyl-terminal fragment (CT) of the beta-amyloid precursor protein (APP) in transgenic animals has been linked with neurotoxicity. However, it remains to be clarified whether the neurotoxicity is caused by beta-amyloid proteins (A betas) derived from CT or by 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 changes in behavior and in brain histology were examined. Animals given CT105 (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 reactive gliosis in neocortex and hippocampus and neurodegeneration in neocortex. These results indicate that centrally administered CT105 induces behavioral impairment and neuropathologic changes, suggesting a direct toxic effect of CT105 per se.
Song
D K
DK
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chunchon, South Korea.
Won
M H
MH
Jung
J S
JS
Lee
J C
JC
Kang
T C
TC
Suh
H W
HW
Huh
S O
SO
Paek
S H
SH
Kim
Y H
YH
Kim
S H
SH
Suh
Y H
YH
D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000737:chemistry; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007276:Injections, Intraventricular; D008124:Locomotion / Q000502:physiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019579:Neocortex / Q000737:chemistry / Q000166:cytology; D010446:Peptide Fragments / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects
D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; C092826:amyloid precursor protein, carboxy-terminal 100 residues