title: Phospholipid and phospholipid metabolites in rat frontal cortex are decreased following nucleus basalis lesions.
abstract: Membrane phospholipid metabolism is abnormal in Alzheimer's disease (AD) brain. Phosphatidylcholine and phosphatidylethanolamine levels are decreased as are choline and ethanolamine, while glycerophosphocholine (GPC) and glycerophosphoethanolamine are increased. To develop a rat model for these changes, we examined the effects of unilateral lesion of the cholinergic nucleus basalis (nBM) with ibotenic acid (10 mg/ml in PBS, 0.5 microliter) and sham lesion on frontocortical phospholipid, choline and GPC. After one week, choline acetyltransferase activity in frontal cortex was decreased (26%, p < 0.005, n = 14) on the nBM ibotenate-lesion side relative to the contralateral side, while there were no differences following the nBM sham-lesion. Levels of membrane phospholipids (nmol/mg protein) in adjacent frontal cortex sections exhibited concomitant decreases (13%, p < 0.05, n = 14) on the nBM ibotenate-lesion side, while there were no differences following the nBM sham-lesion. Tissue nBM ibotenate-lesion frontocortical choline and GPC levels were also decreased relative to those in control tissue (choline: 21%, p < 0.05, n = 14; GPC: 10%, p < 0.05, n = 14), while nBM sham-lesion showed no effect. Muscarinic receptor sensitivity in frontal cortex following nBM ibotenate-lesion was increased, as measured by carbachol-stimulated inositol phosphate production (p < 0.001, n = 12), indicating that increased receptor mediated phospholipid hydrolysis in cortex may occur following nBM ibotenate-lesion. These data suggest that impaired cholinergic transmission alters phospholipid metabolism in cholinergic target regions.
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
authors.forename: T C
authors.initials: TC
authors.lastname: Holmes
authors.forename: R M
authors.initials: RM
authors.lastname: Nitsch
authors.forename: A
authors.initials: A
authors.lastname: Erfurth
authors.forename: R J
authors.initials: RJ
authors.lastname: Wurtman
mesh_terms: D000818:Animals; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D019856:Ethanolamine; D004983:Ethanolamines / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism*; D007839:Functional Laterality; D007051:Ibotenic Acid / Q000633:toxicity; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism; D013377:Substantia Innominata / Q000502:physiology*
chemical_list: D004983:Ethanolamines; D010743:Phospholipids; D011976:Receptors, Muscarinic; D007051:Ibotenic Acid; D019856:Ethanolamine; D002795:Choline O-Acetyltransferase; D002794:Choline