Ibotenic acid-induced lesions of the medial septum increase hippocampal membrane associated protein kinase C activity and reduce acetylcholine synthesis: Prevention by a phosphatidylcholine/vitamin B12 diet

Mei Chu Hung, Koji Shibasaki, Shoko Nishizono, Masao Sato, Ikuo Ikeda, Yasunobu Masuda, Masaaki Kunou, Mitsuru Kawamura, Motoji Yamashita, Shinpei Inoue, Katsumi Imaizumi

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Abstract

Ibotenic acid infusion into the medial septum (MS) results in biochemical alterations in the hippocampus. The biochemical events involved in this neuronal lesion are poorly understood. We investigated the effect of a purified diet supplemented with egg phosphatidylcholine (PC) and vitamin B12 on ibotenic acid-medicated biochemical changes in the rat hippocampus and crude synaptosomal membranes. Male Wistar rats with this MS lesion were fed a purified diet (control diet) or a purified diet supplemented with 5.7 g PC and 125 μg vitamin B12 per 100 g (experimental diet) for 18 days. Sham-operated rats were fed the control diet. Compared with the sham-operated rats, MS-lesioned rats fed the control diet showed increased activity of membrane-bound protein kinase C (PKC), decreased activity of choline acetyltransferase, and decreased concentrations of acetylcholine in the hippocampus. The ratio of cholesterol to phospholipid in the crude synaptic membrane was lower in the lesioned rats than in the sham-operated rats, but this was not accompanied by any alteration in membrane lipid fluidity. MS-lesioned rats fed the experimental diet showed lowered PKC activity and elevated acetylcholine concentrations than did rats fed the control diet, but there were no significant effects on choline acetyltransferase activity and the lipid ratio. The ibotenic acid-mediated elevation of PKC activity was observed as early as 2 days postinjury in the control diet-fed rats but not in the experimental diet-fed rats. We propose that ibotenic acid mediates pathophysiologic actions through the activation of PKC and that PC combined with vitamin B12 ameliorates the second messenger-mediated injury. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)159-164
Number of pages6
JournalJournal of Nutritional Biochemistry
Volume11
Issue number3
DOIs
Publication statusPublished - Mar 1 2000
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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