Differential changes of nicotinic receptors in the rat brain following ibotenic acid and 192-IgG saporin lesions of the nucleus basalis magnocellularis.
The basal forebrain cholinergic neurons are implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD). The nicotinic acetylcholine receptors (nAChRs) have been found to be significantly afflicted in AD. To study the underlying mechanisms for dysfunction of the basal forebrain cholinergic neurons development of suitable animal models is warranted. In this study we investigated the effects of bilateral lesions of the nucleus basalis magnocellularis on nAChRs in the rat brain using the cholinergic system selective immunotoxin 192-IgG saporin and non-selective excitotoxin ibotenic acid. Changes in nAChRs were measured by 3H-cytisine and 3H-epibatidine, two ligands with different selectivity for nAChRs subtypes. In the parietal cortex of ibotenic acid lesioned rates, the choline acetyltransferase activity (ChAT) was decreased by 24% while no changes were detected in the frontal cortex or hippocampus. Similarly, a 40% decrease was observed in the number of nAChRs labelled by 3H-cytisine, but not by 3H-epibatidine, in the parietal cortex, while no changes were found in the frontal cortex or hippocampus. Although the 192-IgG saporin induced lesions reduced the ChAT activity in the frontal cortex, parietal cortex and hippocampus by 77, 50 and 21%, respectively, no changes were observed in the number of nAChRs as studied by 3H-cytisine or 3H-epibatidine. The results indicate a difference in vulnerability of the cortical nAChR subtypes to experimental lesions of the nucleus basalis magnocellularis. The findings in this study suggest that a major portion of the nAChRs might be located on non-cholinergic neurons in the brain.
Bednar
I
I
Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
Zhang
X
X
Dastranj-Sedghi
R
R
Nordberg
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D018678:Cholinergic Agents / Q000633:toxicity*; D007051:Ibotenic Acid / Q000633:toxicity*; D000922:Immunotoxins / Q000633:toxicity*; D008297:Male; D009699:N-Glycosyl Hydrolases; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013377:Substantia Innominata / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D011978:Receptors, Nicotinic; D054789:Ribosome Inactivating Proteins, Type 1; D007051:Ibotenic Acid; D009699:N-Glycosyl Hydrolases; D000076985:Saporins