Differential changes of nicotinic receptors in the ratbrain following ibotenic acid and 192‐IgG saporin lesionsof the nucleus basalis magnocellularis

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Abstract
The basal forebrain cholinergic neurons are implicated in the pathogenesis ofneurodegenerative diseases including Alzheimer fn2 fn2 s disease ; IBO, ibotenic acid ;nAChR, nicotinic acetylcholine receptor ; NBM, nucleus basalis magnocellularis. s disease (AD). The nicotinic acetylcholine receptors (nAChRs) have been found to besignificantly afflicted in AD. To study the underlying mechanisms for dysfunction of the basalforebrain cholinergic neurons development of suitable animal models is warranted. In this studywe investigated the effects of bilateral lesions of the nucleus basalis magnocellularis on nAChRs inthe rat brain using the cholinergic system selective immunotoxin 192-IgG saporin andnon-selective excitotoxin ibotenic acid. Changes in nAChRs were measured by 3 H-cytisineand 3 H-epibatidine, two ligands with different selectivity for nAChRs subtypes. Inthe 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 3 H-cytisine,but not by 3 H-epibatidine, in the parietal cortex, while no changes were found in thefrontal cortex or hippocampus. Although the 192-IgG saporin induced lesions reduced the ChATactivity in the frontal cortex, parietal cortex and hippocampus by 77, 50 and 21%, respectively, nochanges were observed in the number of nAChRs as studied by 3 H-cytisine or 3 H-epibatidine. The results indicate a difference in vulnerability of the cortical nAChRsubtypes to experimental lesions of the nucleus basalis magnocellularis. The findings in this studysuggest that a major portion of the nAChRs might be located on non-cholinergic neurons in thebrain.
Funding Information
  • Medicinska Forskningsrådet (No. 05817)
  • Loo och Hans Ostermans Stiftelse för Medicinsk Forskning
  • Stiftelsen för Gamla Tjänarinnor

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