Cholinergic Projection from the Basal Forebrain and Cerebral Glucose Metabolism in Rats: A Dynamic PET Study

Abstract

To investigate the influence of cholinergic projections from the basal forebrain on cerebral cortex metabolism, we evaluated the cerebral metabolic rate of glucose (CMRGlu) after selective inhibition of cholinergic neurons in the rat basal forebrain using the pyruvate dehydrogenase complex inhibitor 3-bromopyruvic acid (BPA), and compared the results with those obtained after lesioning the basal forebrain with ibotenic acid, as well as with those from a sham-operated control group. CMRGlu was measured using positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG). Three days after surgery, CMRGlu and k3 (phosphorylation of FDG) were reduced similarly in the frontal cortex on the BPA-injected side and in the ibotenic acid-treated group, whereas K1 (transport rate of FDG from the plasma to brain) showed no marked changes. At 3 weeks postoperatively, the CMRGlu and k3 of the frontal cortex in both groups recovered to levels similar to those of the sham-operated group. The main difference between the BPA and ibotenic acid groups was that CMRGlu showed mild reduction on the side contralateral to the operation in the former, while such reduction was confined to the ipsilateral hemisphere in the latter. The present results indicate that the cholinergic system in the basal forebrain regulates cerebral cortex glucose metabolism through direct excitation of cortical neurons.

Uncoupling of Blood Flow and Metabolism in Focal Epilepsy

“…Therefore, a differential regulation of cerebral blood flow and metabolism may be assumed. In recent reports, a remote neuronal control of metabolism has been described for cortical areas that are metabolically influenced by the basal forebrain (40). The results of our group point toward a similar mechanism in this model: The high synchronized activity in the motor cortex is associated with an increase of metabolism mainly in the nucleus posterior (35) of the thalamus, which sends diffuse inputs to the somatosensory cortical areas.…”

“…12, 1998 has been suggested that local vasoactive factors play a role on a short-term, dynamic basis, and capillary density involved on a long-term, static basis (39). Factors participating in coupling of these two parameters include ion concentrations, blood-gas tension, neurotransmitters (40), neuropeptides, and local neuronal vascular control.…”

Selective Antibody-Induced Cholinergic Cell and Synapse Loss Produce Sustained Hippocampal and Cortical Hypometabolism with Correlated Cognitive Deficits

“…Typically, glucose use was depressed 3-4 days postexcitotoxin-lesion, but recovered to basal levels within 4 weeks after unilateral lesions, and 4 months following bilateral lesions despite sustained ChAT deficits (9,37,44,47,60,61,80). This functional recovery most likely reflects the lack of cholinergic selectivity of these lesion paradigms, leading to incomplete cholinergic denervation.…”

“…Hence glucose use changes seen 18 weeks postcholinergic neuronal loss reflect alterations in well organized, functional pathways associated with the basal forebrain cholinergic system. Several previous studies in both rats and baboons used different lesion paradigms to assess glucose utilization after disrupting BF cholinergic projections (9,37,44,47,60,61,80). However, these investigations were compromised by the lack of a discrete, selective cholinotoxin.…”

Cerebral Blood Flow during Spontaneous and Cholinergically Induced Behavioral States in the Sheep Fetus

“…Evidence also exists for the cholinergic system's role in the regulation of CBF in adults. Cholinergic neurons in the basal forebrain play a role in the regulation of CMR (13), and injection of the cholinergic agonist carbachol into the substantia innominata increases CBF in rats. This effect can be blocked in some cortical regions by systemic treatment with scopolamine, a cholinergic antagonist (14).…”