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 cholineacetyl 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.