Local and distant histopathological effects of unilateral amyloid-beta 25-35 injections into the amygdala of young F344 rats.
To determine if amyloid-beta (A beta) induces tau-immunoreactivity (IR) and reactive astrocytosis in vivo, we injected A beta 25-35 (5.0 nmol) into the right amygdala of rats. At 8 days postinjection, the peptide induced tau-2 IR in neuronal cell bodies and processes ipsilaterally in the amygdala, cingulate cortex, and hippocampus. At 32 days postinjection, the intensity of tau-2 IR was greater than at 8 days in the amygdala and hippocampus, but not in the cingulate cortex. Induction of Alz-50 IR also was progressive but the morphology and distribution was different from tau-2 IR. Beaded fibers with occasional neuronal perikarya were visualized with Alz-50, and the IR was primarily observed in the ipsilateral amygdala. In addition, amygdaloid injections of A beta 25-35 induced reactive astrocytosis, particularly in the ipsilateral hippocampus at 32 days postoperatively. To our knowledge, this is the first study to show that in vivo injections of A beta 25-35 induce progressive transsynaptic cytoskeletal and astrogliotic reactions, that gradually spread from the area of injection to brain regions that have prominent efferent connections with that area. These findings also suggest a direct association between plaque and tangle formation in Alzheimer's disease.
Sigurdsson
E M
EM
Department of Pharmacology, Loyola University Chicago Medical Center, Maywood, IL 60153, USA.
Lorens
S A
SA
Hejna
M J
MJ
Dong
X W
XW
Lee
J M
JM
D000679:Amygdala / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000941:Antigens / Q000378:metabolism; D048588:Benzoxazines; D001921:Brain / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008845:Microinjections; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity*; D010078:Oxazines; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D016875:tau Proteins / Q000378:metabolism
C056167:Alzheimer's disease antigen; D016229:Amyloid beta-Peptides; D000941:Antigens; D048588:Benzoxazines; D005904:Glial Fibrillary Acidic Protein; D009498:Neurotoxins; D010078:Oxazines; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D016875:tau Proteins; C028911:cresyl violet