title: Short- and long-term effects of nucleus basalis magnocellularis lesions on cortical levels of somatostatin and its receptors in the rat.
abstract: Cognitive and histological alterations in human Alzheimer's disease (AD) are correlated with selective neuronal loss in nucleus basalis of Meynert. In search of an animal model of AD-linked neurochemical deficits, we examined the effects of short- (2 weeks) and long- (3 and 6 months) term lesions of the nucleus basalis magnocellularis (NBM) on somatostatinergic parameters in rat forebrain. NBM lesions were performed by unilateral injection of ibotenic acid into the NBM. Cortical choline-acetyl transferase (ChAT) activity and acetylcholinesterase staining in the NBM remained significantly decreased ipsi- as compared to contralaterally up to 6 months after the placement of the lesion. Somatostatin (SRIF) content was increased by 120% in the ipsilateral frontal cortex 6 months post-lesion but not at shorter time intervals. Levels of neuropeptide Y (which is extensively co-localized with SRIF in the forebrain) were not significantly altered after unilateral NBM lesions at any time point. A 30% decrease in SRIF binding capacity as well as a marked reduction of SRIF inhibition of adenylate cyclase, indicative of a loss of functional SRIF receptors, was observed in ipsilateral versus contralateral frontal cortex on brain tissue homogenates after short-term unilateral NBM lesion. By film radioautography, the loss in SRIF binding sites was localized to both superficial and deep layers of the frontal cortex. This loss persisted up to 3 months but was no longer apparent after 6 months due to a decrease in SRIF binding capacity on the contralateral side.
authors.affiliation: U159 INSERM, Centre Paul Broca, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Moyse
authors.forename: E
authors.initials: E
authors.lastname: Szigethy
authors.forename: J M
authors.initials: JM
authors.lastname: Danger
authors.forename: H
authors.initials: H
authors.lastname: Vaudry
authors.forename: G L
authors.initials: GL
authors.lastname: Wenk
authors.forename: A
authors.initials: A
authors.lastname: Beaudet
authors.forename: J
authors.initials: J
authors.lastname: Epelbaum
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D006651:Histocytochemistry; D007051:Ibotenic Acid / Q000008:administration & dosage / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects; D009478:Neuropeptide Y / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000378:metabolism*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D007457:Iodine Radioisotopes; D009478:Neuropeptide Y; D017481:Receptors, Somatostatin; D007051:Ibotenic Acid; D013004:Somatostatin; D000262:Adenylyl Cyclases