Phospholipid and phospholipid metabolites in rat frontal cortex are decreased following nucleus basalis lesions.
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.
Holmes
T C
TC
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Nitsch
R M
RM
Erfurth
A
A
Wurtman
R J
RJ
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*
D004983:Ethanolamines; D010743:Phospholipids; D011976:Receptors, Muscarinic; D007051:Ibotenic Acid; D019856:Ethanolamine; D002795:Choline O-Acetyltransferase; D002794:Choline