Original Contribution
Journal of Cerebral Blood Flow & Metabolism (1998) 18, 476–490; doi:10.1097/00004647-199805000-00003
Effects of Damage to the Basal Forebrain on Brain Glucose Utilization: A Reevaluation Using Positron Emission Tomography in Baboons With Extensive Unilateral Excitotoxic Lesion
Partial funding was provided by a grant from the University of Caen; C. Le Mestric was supported by a PhD Scholarship from the Ministère de la Recherche et de l'Enseignement Supérieur.
Claude Le Mestric*, Chantal Chavoix*, Françoise Chapon†, Florence Mézenge*, Jacques Epelbaum‡ and Jean Claude Baron*
- *INSERM U. 320, CYCERON/CEA DSV DPTE, University of Caen, Paris, France.
- †Service de Neurologie Déjerine, CHU de Caen, Paris, France.
- ‡INSERM U. 159, Paris, France.
Correspondence: Jean Claude Baron, INSERM U. 320, CYCERON, BP 5229, 14074 CAEN, France.
Received 17 July 1997; Revised 27 October 1997; Accepted 27 October 1997.
Abstract
Neuronal loss in the basal forebrain cholinergic structures and frontotemporal hypometabolism are two characteristics of Alzheimer's disease, but their interrelations still are unsettled. We previously reported that unilateral electrolytic lesions of the nucleus basalis of Meynert in baboons were associated with marked but transient cortical hypometabolism. The current study reevaluates this issue using improved methodology. Baboons with unilateral ibotenic acid lesion of all three basal forebrain cholinergic structures (IBO group) were compared with sham-operated animals. The CMRglc was measured with high-resolution coronal positron emission tomography scanning coregistered with magnetic resonance imaging, before surgery and serially between 4 and 72 days afterward. Severe histologic basal forebrain damage and a decrease of more than 50% in cortical choline acetyltransferase activity were found postmortem in the IBO group. Transient and non-specific hypometabolism was found in the needle track area in both groups. Compared with the sham-operated group, only marginally significant decreases in ipsilateral-contralateral CMRglc ratios were observed in the IBO group, affecting only 1 of 14 neocortical areas investigated (the anterior temporal cortex) at a single postsurgical time (day 14), and the posterior hippocampal region at days 14 and 38. Furthermore, there was no consistently significant correlation between ipsilateral-contralateral CMRglc ratios and cortical choline acetyltransferase activity values in any of the four regions analyzed. These results suggest that cholinergic deafferentation play at best a marginal role in the brain hypometabolism observed in Alzheimer's disease.
Keywords:
Acetylcholine, Nucleus of Meynert, Alzheimer's disease, 18F-fluoro-2-deoxy-D-glucose, Nonhuman primate
Abbreviations:
AD, Alzheimer's disease; ANOVA, analysis of variance; BF, basal forebrain; ChAT, choline acetyltransferase; DB, diagonal band of Broca; DBh, horizontal limb of the diagonal band of Broca; DBv, vertical limb of the diagonal band of Broca; I/C ratio, ipsilateral-contralateral ratio; MR, magnetic resonance; MS, medial septum; NB, nucleus basalis of Meynert; NBal, anterior lateral neuronal group of the nucleus basalis of Meynert; NBam, anterior medial neuronal group of the nucleus basalis of Meynert; NBid, dorsal intermediate group of the nucleus basalis of Meynert; NBiv, ventral intermediate group of the nucleus basalis of Meynert; NBp, posterior group of the nucleus basalis of Meynert; NBM, nucleus basalis magnocellularis; pAC, posterior edge of the anterior commissure; PET, positron emission tomography; ROI, region(s) of interest
