The acute neurotoxicity and effects upon cholinergic axons of intracerebrally injected beta-amyloid in the rat brain.
The acute neurotoxicity and effects upon cholinergic axons of an intracerebrally injected synthetic peptide corresponding to the first 1-40 amino acids of beta-amyloid protein (beta AP1-40) was studied in rats. A synthetic peptide with the reverse sequence (beta AP40-1) or the vehicle alone were injected in the contralateral hemisphere as control. The size of the resulting lesions was quantified in serial sections using an image analyzer. Counts of cholinergic and noradrenergic fibers were also obtained around the lesion area. The results revealed that beta AP1-40 was significantly more toxic than both reverse peptide and the vehicle. The latter two, however, also caused considerable neurotoxicity. beta AP1-40 was toxic to both cholinergic and noradrenergic fibers to the same extent, and this toxicity was limited to the immediate vicinity of the lesion. This study confirms and extends the results of previous studies reporting neurotoxic effects of intracerebrally injected beta-amyloid in the rat. Our results also show that beta AP1-40 itself is not the source of the altered acetylcholinesterase enzyme activity that has been described in the plaques and tangles of Alzheimer's disease.
Emre
M
M
Bullard and Denny-Brown Laboratories, Beth Israel Hospital, Boston, MA 02215.
Geula
C
C
Ransil
B J
BJ
Mesulam
M M
MM
D000110:Acetylcholinesterase / Q000378:metabolism; D000320:Adrenergic Fibers / Q000187:drug effects; D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001369:Axons / Q000187:drug effects*; D001921:Brain; D002540:Cerebral Cortex / Q000473:pathology; D002799:Cholinergic Fibers / Q000187:drug effects; D002802:Cholinesterases / Q000378:metabolism; D006651:Histocytochemistry; D007267:Injections; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D000110:Acetylcholinesterase; D002802:Cholinesterases