Hippocampal beta-amyloid reduces locus coeruleus glutamate and tyrosine hydroxylase.
The effects of intrahippocampally injected beta-amyloid protein (beta-AP) on glutamate- (Glu) and tyrosine hydroxylase (TH)-like immunoreactivities in the neurons of the locus coeruleus (LC) were studied in rats. A synthetic peptide or the vehicle alone was injected into the hippocampus as controls. All injections were made once a week (two or three injections; 3 nmol in 2 microliters of distilled water). Fluorescent microspheres (either alone or with one of the peptides) were also injected into the hippocampus to identify coeruleo-hippocampal neurons. The results revealed cell loss in the hippocampus at the site near beta-AP or control peptide deposition. Furthermore, in beta-AP/microsphere injected animals, only 22.4% and 49.6% of hippocampal projection neurons contained Glu and TH, respectively, compared to 88.4% and 85.3% in the animals that received control peptide with microspheres. Our results suggest that beta-AP has an effect on noradrenergic cells whose axons project to the hippocampus. These effects may contribute to the TH cell loss in the LC of Alzheimer's brains.
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman 99164-6520.
Z
Z
Wang
R H
RH
Liu
V K
VK
Reddy
C D
CD
Barnes
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D007267:Injections; D008125:Locus Coeruleus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D018698:Glutamic Acid; D014446:Tyrosine 3-Monooxygenase