Cortical Hypometabolism and Its Recovery Following Nucleus Basalis Lesions in Baboons: A PET Study (original) (raw)
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Journal of Cerebral Blood Flow & Metabolism, 1998
Neuronal loss in the basal forebrain cholinergic structures and frontotemporal hypometabolism are two charac teristics 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 meth odology. Baboons with unilateral ibotenic acid lesion of all three basal forebrain cholinergic structures (IBO group) were compared with sham-operated animals. The CMRglc was mea sured with high-resolution coronal positron emission tomogra phy 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-Abbreviations used: 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; IIC ratio, ipsilateral-contralateral ratio; MR, magnetic resonance; MS, medial septum; NB, nucleus basalis of Meynert; NBal, anterior lateral neuro nal group of the nucleus basalis of Meynert; NBam, anterior medial neuronal group of the nucleus basalis of Meynert; NBid, dorsal inter mediate group of the nucleus basalis of Meynert; NBiv, ventral inter mediate group of the nucleus basalis of Meynert; NBp, posterior group of the nucleus basalis of Meynert; NBM, nucleus basalis magnocellu laris; pAC, posterior edge of the anterior commissure; PET, positron emission tomography; ROI, region(s) of interest. 476 10-17 Vaucher E, Borredon J, Bonvento G, Seylaz J, Lacombe P (1997) Autoradiographic evidence for flow-metabolism uncoupling dur ing stimulation of the nucleus basalis of Meynert in the conscious rat. J Cereb Blood Flow Metab 17:686-694 Voytko ML, Olton DS, Richardson RT, Gorman LK, Tobin JR, Price DL (1994) Basal forebrain lesions in monkeys disrupt attention but not learning and memory. J Neurosci 14: 167-186 Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, DeLong MR (1982) Alzheimer's disease and senile dementia: loss of neu rons in the basal forebrain. Science 215:1237-1239 Wilcock GK, Esiri MM, Bowen DM, Smith CCT (1982) Alzheimer disease: correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities. J Neurol Sci 57 :407-4 17 Yamaguchi T, Kunimoto M, Pappata S, Chavoix C, Brouillet E, Riche D, Maziere M, Naquet R, MacKenzie ET, Baron JC (1990) Effects of unilateral lesion of the nucleus basalis of Meynert on brain glucose utilization in callosotomized baboons: a PET study. J Cereb Blood Flow Metab 10:618-623
Journal of Cerebral Blood Flow & Metabolism, 1990
Prior work has demonstrated that unilateral lesions of the nucleus basalis of Meynert (NbM) in ba boons induce a marked reduction in glucose utilization of the ipsilateral cerebral cortex, linearly proportional to the depression in cortical choline acetyltransferase (ChAT) activity achieved. Unexpectedly, there was also marked hypometabolism of the contralateral cerebral cortex, and glucose utilization recovered gradually on both sides de spite persistent deficit in cortical ChAT activity. To in vestigate the role of the corpus callosum (CC) in this bi lateral metabolic effect and subsequent recovery, three baboons were subjected to unilateral electrolytic NbM lesion >3 months following section of the anterior CC. Brain glucose utilization was sequentially studied by pos-
Brain, 1999
Temporoparietal glucose hypometabolism, neuronal loss in the basal forebrain cholinergic structures and preferential accumulation of neurofibrillary tangles in the rhinal cortex (i.e. in the entorhinal and perirhinal cortices) are three early characteristics of Alzheimer's disease. Based on studies of the effects of neurotoxic lesions in baboons, we previously concluded that damage to the cholinergic structures plays, at best, a marginal role in the association neocortex hypometabolism of Alzheimer's disease. In the present study, we have assessed the remote metabolic effects of bilateral neurotoxic lesions of both entorhinal and perirhinal cortices. Using coronal PET coregistered with MRI, the cerebral metabolic rate for glucose (CMR glc ) was measured before surgery and sequentially for 2-3 months afterward (around days 30, 45 and 80). Compared with sham-operated baboons, the lesioned animals showed a significant and long-lasting CMR glc decline in a small set of brain regions, especially in the inferior parietal, posterior temporal, posterior cingulate and associative occipital Abbreviations: ANOVA ϭ analysis of variance; CMR glc ϭ cerebral metabolic rate for glucose; FDG ϭ [ 18 F]fluoro-2-deoxy-D-deoxyglucose; MRA ϭ magnetic resonance angiography; pAC ϭ posterior edge of the anterior commissure; RH ϭ animal which received a lesion in the rhinal cortex; SH ϭ sham-operated animal
Cortical Metabolic Deficits in a Rat Model of Cholinergic Basal Forebrain Degeneration
Neurochemical Research, 2013
Evidence indicates that the degeneration of basal forebrain cholinergic neurons may represent an important factor underlying the progressive cognitive decline characterizing Alzheimer's disease (AD). However, the nature of the relationship between cholinergic depletion and AD is not fully elucidated. This study aimed at clarifying some aspects of the relation existing between deficits in cerebral energy metabolism and degeneration of cholinergic system in AD, by investigating the neuronal metabolic activity of several cortical areas after depletion of basal forebrain cholinergic neurons. In cholinergically depleted rats, we evaluated the neuronal metabolic activity by assaying cytochrome oxidase (CO) activity in frontal, parietal and posterior parietal cortices at four different timepoints after unilateral injection of 192 IgG-saporin in the nucleus basalis magnocellularis. Unilateral depletion of cholinergic cells in the basal forebrain induced a bilateral decrease of metabolic activity in all the analyzed areas. Frontal and parietal cortices showed decreased metabolic activity even 3 days after the lesion, when the cholinergic degeneration was still incomplete. In posterior parietal cortex metabolic activity decreased only 7 days after the lesion. The possible molecular mechanisms underlying these findings were also investigated. Real-time PCR showed an increase of CO mRNA levels at 3, 7 and 15 days after the lesion both in frontal and parietal cortices, followed by normalization at 30 days. Western Blot analysis did not show any change in CO protein levels at any time-point after the lesion. Our findings support a link between metabolic deficit and cholinergic hypofunctionality characterizing AD pathology. The present model of cholinergic hypofunctionality provides a useful means to study the complex mechanisms linking two fundamental and interrelated phenomena characterizing AD from the early stages.
Basal Ganglia and Frontal Lobe Glucose Metabolism
Journal of Neuroimaging, 1995
Pos1tron emission tomography (PET) w1th '"F-fluoro-2-deoxy-Dglucose (FDG) 1s frequently used to study the metabolic correlates of movement and mental d1sorders. These stud1es generally focus on changes in the frontal cortex and the basal gangl1a. The reproducibility of glucose metabol1sm est1mates in these structures was tested 1n 13 normal subjects stud1ed at rest usmg a standard and s1mple protocol. A reproducible dorsoventral metabol1c gradient was demonstrated 1n the frontal cortex. Such a grad1ent was not present m the basal gangl1a when the upper region of interest 1n the caudate nucleus, where the lower metabol1c rate of glucose was probably attnbutable to part1al volume effects, was not considered. Absolute values of glucose metabolic rates varied by 6.4 to 12.5% m the frontal cortex and by 6.8 to 14.7% in the basal gangl1a. Vamt1ons 1n normal1zed values in the basal gangl1a ranged from 4.0 to 8.6%. The number of subjects requ1red to detect statistical differences in group companson or m test-retest stud1es was calculated for different anticipated levels of change. W1th the variability detected in this expenment, less than 10 subjects were expected to be suff1c1ent to detect a 15% change in most regions and in both types of stud1es.
Cerebral Glucose Metabolism in Parkinson's Disease With and Without Dementia
Archives of Neurology, 1992
Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using l8 F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra. RESUME: Nous avons mesure 1'utilisation locale du glucose dans le cerveau de patients ayant surtout un Parkinson uniliteral. Nous utilisions pour ce faire la tomographic par emission de positron et le l8 F-2-fluoro-2-deoxyglucose. Les resultats preliminaires indiquent la presence de taux metaboliques asymmetriques dans les noyaux gris centraux inferieurs, surtout le globus pallidus. Ces resultats sont compatibles avec les etudes experimentales chez des animaux avec lesion unilateral des voies nigro-striees, animaux chez lesquels un hypermetabolisme pallidal avait ete note du cote de la lesion. Cette activite pallidale augmentee est probablement secondaire a la perte des influx dopaminergiques inhibiteurs provenent de la substance noire et agissant au striatum.
Annals of Neurology, 1989
Nine positron emission tomography studies of regional cerebral glucose metabolism were performed in 7 patients with probable striatonigral degeneration, a disorder characterized by parkinsonian features and absent or poor response to L-dopa When compared with values obtained in normal volunteers, mean cerebral glucose metabolism was slightly reduced in subjects with striatonigral degeneration who, in addition, had a marked (20.596, +-3 SD) relative hypometabolism in putaminal and caudate nuclei. Significant hypometabolism was also found in motor/premotor as well as in prefrontal cortex. In 2 subjects who were studied twice a deterioration of relative striatal metabolism paralleled clinical evolution. Magnetic resonance imaging disclosed the presence of abnormal iron deposits in the putamen in all cases but showed no cortical anomalies. These results suggest that positron emission tomography with f: '*F}fluorodeoxyglucose may provide an index of cell and processes degeneration in the striatum in striatonigral degeneration and is able to detect functional deficits in frontal cortex. The presence of striatal hypometabolism might be a predictor of a poor response to L-dopa.
Hypometabolism of the posterior cingulate cortex is not restricted to Alzheimer's disease
Alzheimer's & Dementia, 2015
When differential diagnosis of dementia includes both Alzheimer's disease (AD) and the behavioural variant of frontotemporal dementia (bvFTD), distribution of cerebral glucose metabolism as measured using [ 18 F]-2-fluoro-2-deoxy-D-glucose positron emission tomography ([ 18 F]FDG-PET) may be helpful. One important clue for differentiation is the presence of hypometabolism in the posterior cingulate cortex (PCC), usually associated with AD. PCC hypometabolism however, could also be present in bvFTD. Therefore, the specificity of PCC hypometabolism was examined. Based on visual reading PCC hypometabolism was present in 69-73/81 probable AD patients, in 10-16/33 probable bvFTD patients, and in 0-1/22 cognitive normal (CN) subjects. Findings were validated using a PCC to reference tissue [ 18 F]FDG standard uptake value ratio (SUVr) cutoff , which was derived from the receiver operating characteristic (ROC) separating probable AD from CN, resulting in 9-14/33 bvFTD patients having PCC hypometabolism, depending on the reference tissue used. In conclusion, PCC hypometabolism is not restricted to AD.