Yonsei Med J.  2016 Jan;57(1):165-172. 10.3349/ymj.2016.57.1.165.

Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex

• Jeong DU
• Oh JH
• Lee JE
• Lee J
• Cho ZH
• Chang JW
• Chang WS

• KMID: 2466366
• DOI: http://doi.org/10.3349/ymj.2016.57.1.165

Abstract

PURPOSE
Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits.
MATERIALS AND METHODS
We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography.
RESULTS
During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex.
CONCLUSION
Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

Keyword

Positron emission tomography; cholinergic neurons; cingulate gyrus; 192 IgG-saporin

MeSH Terms

Acetylcholine/metabolism
Alzheimer Disease
Animals
Antibodies, Monoclonal/*pharmacology
Basal Forebrain/*drug effects/metabolism
Cholinergic Agents/administration & dosage/*pharmacology
Cholinergic Neurons/*drug effects/metabolism
Fluorodeoxyglucose F18
GABAergic Neurons/*drug effects/metabolism
Glucose/*metabolism
Gyrus Cinguli/*drug effects/metabolism
Humans
Injections
Maze Learning
Motor Activity/physiology
Positron-Emission Tomography
Rats
Ribosome Inactivating Proteins, Type 1/*pharmacology
Acetylcholine
Antibodies, Monoclonal
Cholinergic Agents
Fluorodeoxyglucose F18
Glucose
Ribosome Inactivating Proteins, Type 1