title: Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science & Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Da Un
authors.initials: DU
authors.lastname: Jeong
authors.affiliation: Neuroscience Research Institute, Gachon University, Incheon, Korea.
authors.forename: Jin Hwan
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science & Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science & Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jihyeon
authors.initials: J
authors.lastname: Lee
authors.affiliation: Neuroscience Research Institute, Gachon University, Incheon, Korea.
authors.forename: Zang Hee
authors.initials: ZH
authors.lastname: Cho
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science & Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.|Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea. jchang@yuhs.ac.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea. changws0716@yuhs.ac.
authors.forename: Won Seok
authors.initials: WS
authors.lastname: Chang
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D066187:Basal Forebrain / Q000187:drug effects* / Q000378:metabolism; D018678:Cholinergic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D059329:Cholinergic Neurons / Q000187:drug effects* / Q000378:metabolism; D019788:Fluorodeoxyglucose F18; D059330:GABAergic Neurons / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007267:Injections; D018782:Maze Learning; D009043:Motor Activity / Q000502:physiology; D049268:Positron-Emission Tomography; D051381:Rats; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology*; D000076985:Saporins
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D054789:Ribosome Inactivating Proteins, Type 1; D019788:Fluorodeoxyglucose F18; D000076985:Saporins; D005947:Glucose; D000109:Acetylcholine
keywords: 192 IgG-saporin; Positron emission tomography; cholinergic neurons; cingulate gyrus