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.
Wang
Z
Z
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman 99164-6520.
Liu
R H
RH
Reddy
V K
VK
Barnes
C D
CD
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