Elevated phosphocholine and phosphatidylcholine following rat entorhinal cortex lesions.
At early stages of Alzheimer's disease, phosphomonoesters (PMEs) including phosphocholine (P-choline) are present at elevated levels. PMEs also are elevated in the developing brain during the period of neurite extension. To determine if the elevation of PMEs in AD could reflect neuritic sprouting, 31P-NMR was used to examine phospholipid metabolites and membrane phospholipids at various times following unilateral lesions of the entorhinal cortex, a well-defined model of neuritic sprouting. Two to 7 days postlesion, P-choline levels were elevated 48% in the hippocampus ipsilateral to the entorhinal cortex lesion, but not in the contralateral hippocampus or cerebral cortex. P-choline levels declined by day 15, and reached control levels 45 days following the lesion. The lesion-induced elevation in P-choline could result from increased P-choline synthesis via choline kinase, decreased activity of CTP:phosphocholine cytidylyltransferase, or breakdown of phosphatidylcholine (PC). To distinguish between these possibilities, the membrane phospholipids PC and phosphatidylethanolamine (PE) were measured. Both phospholipids were maintained at or above control levels at each of the postlesion time points, arguing against membrane breakdown or decreased PC synthesis contributing to the elevation of P-choline levels. Other alterations included a widespread elevation in inositol phosphate 2 days postlesion, but not at later time points. The alterations in phospholipid metabolites observed in the rat hippocampus following entorhinal cortex lesions closely resemble those observed in the human brain in the early stages of AD.
Geddes
J W
JW
Sanders-Brown Center on Aging, University of Kentucky, Lexington 40536, USA.
Panchalingam
K
K
Keller
J N
JN
Pettegrew
J W
JW
D000818:Animals; D018728:Entorhinal Cortex / Q000378:metabolism* / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D010767:Phosphorylcholine / Q000378:metabolism*; D051381:Rats
D010713:Phosphatidylcholines; D010767:Phosphorylcholine