Effects of Aging and Amyloid-beta Peptides on Choline Acetyltransferase Activity in Rat Brain

Overview

Journal Neurochem Res

Specialties Chemistry
Neurology

Date 2002 Apr 18

PMID 11958528

Citations 7

Authors

Agata Zambrzycka

Mario Alberghina

Joanna B Strosznajder

Affiliations

Soon will be listed here.

Abstract

Choline acetyltransferase (ChAT, acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6), involved in the learning and memory processes is responsible for the synthesis of acetylcholine. There are many discrepancies in literature concerning ChAT activity during brain aging and the role of amyloid beta peptides in modulation of this enzyme. The aim of the study was to investigate the mechanism of ChAT regulation and age-related alteration of ChAT activity in different parts of the brain. Moreover the effect of Abeta peptides on ChAT activity in adult and aged brain was investigated. The enzyme activity was determined in the brain cortex, hippocampus and striatum in adult (4-months-old), adult-aged (14-months-old) and aged (24-months-old) animals. The highest ChAT activity was observed in the striatum. We found that inhibitors of protein kinase C, A, G and phosphatase A2 have no effect on ChAT activity and that this enzyme is not dependent on calcium ions. About 70% of the total ChAT activity is present in the cytosol. Arachidonic acid significantly inhibited cytosolic form of this enzyme. In the brain cortex and striatum from aged brain ChAT activity is inhibited by 50% and 37%, respectively. The aggregated form of Abeta 25-35 decreased significantly ChAT activity only in the aged striatum and exerted inhibitory effect on this enzyme in adult, however, statistically insignificant. ChAT activity in the striatum was diminished after exposure to 1 mM H2O2. The results from our study indicate that aging processes play a major role in inhibition of ChAT activity and that this enzyme in striatum is selectively sensitive for amyloid beta peptides.

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References

Baxter M, Frick K, Price D, Breckler S, Markowska A, Gorman L . Presynaptic markers of cholinergic function in the rat brain: relationship with age and cognitive status. Neuroscience. 1999; 89(3):771-9. DOI: 10.1016/s0306-4522(98)00374-1. View

Haba K, Ogawa N, Kawata M, Mori A . A method for parallel determination of choline acetyltransferase and muscarinic cholinergic receptors: application in aged-rat brain. Neurochem Res. 1988; 13(10):951-5. DOI: 10.1007/BF00970767. View

Ninomiya Y, Kayama Y . Inhibition of choline acetyltransferase activity by serum albumin modified with octanoic acid and other fatty acids. Neurochem Res. 1998; 23(10):1303-11. DOI: 10.1023/a:1020752418516. View

McGeer E, Fibiger H, McGeer P, Wickson V . Aging and brain enzymes. Exp Gerontol. 1971; 6(6):391-6. DOI: 10.1016/0531-5565(71)90018-0. View

Sirvio J, Hervonen A, Riekkinen P . Cholinergic binding in the hippocampus of the aging male rat. Comp Biochem Physiol C Comp Pharmacol Toxicol. 1988; 90(1):161-3. DOI: 10.1016/0742-8413(88)90113-2. View

Oda Y . Choline acetyltransferase: the structure, distribution and pathologic changes in the central nervous system. Pathol Int. 1999; 49(11):921-37. DOI: 10.1046/j.1440-1827.1999.00977.x. View

Pedersen W, Blusztajn J . Characterization of the acetylcholine-reducing effect of the amyloid-beta peptide in mouse SN56 cells. Neurosci Lett. 1998; 239(2-3):77-80. DOI: 10.1016/s0304-3940(97)00913-0. View

Pedersen W, Kloczewiak M, Blusztajn J . Amyloid beta-protein reduces acetylcholine synthesis in a cell line derived from cholinergic neurons of the basal forebrain. Proc Natl Acad Sci U S A. 1996; 93(15):8068-71. PMC: 38876. DOI: 10.1073/pnas.93.15.8068. View

Benishin C, Carroll P . Acetylation of choline and homocholine by membrane-bound choline-O-acetyltransferase in mouse forebrain nerve endings. J Neurochem. 1981; 36(2):732-40. DOI: 10.1111/j.1471-4159.1981.tb01649.x. View

10.

Kar S, Issa A, Seto D, Auld D, Collier B, Quirion R . Amyloid beta-peptide inhibits high-affinity choline uptake and acetylcholine release in rat hippocampal slices. J Neurochem. 1998; 70(5):2179-87. DOI: 10.1046/j.1471-4159.1998.70052179.x. View

11.

Arita K, Kobuchi H, Utsumi T, Takehara Y, Akiyama J, Horton A . Mechanism of apoptosis in HL-60 cells induced by n-3 and n-6 polyunsaturated fatty acids. Biochem Pharmacol. 2001; 62(7):821-8. DOI: 10.1016/s0006-2952(01)00723-7. View

12.

Fonnum F . A rapid radiochemical method for the determination of choline acetyltransferase. J Neurochem. 1975; 24(2):407-9. DOI: 10.1111/j.1471-4159.1975.tb11895.x. View

13.

Bird T, Stranahan S, SUMI S, Raskind M . Alzheimer's disease: choline acetyltransferase activity in brain tissue from clinical and pathological subgroups. Ann Neurol. 1983; 14(3):284-93. DOI: 10.1002/ana.410140306. View

14.

Hoshi M, Takashima A, Murayama M, Yasutake K, Yoshida N, Ishiguro K . Nontoxic amyloid beta peptide 1-42 suppresses acetylcholine synthesis. Possible role in cholinergic dysfunction in Alzheimer's disease. J Biol Chem. 1997; 272(4):2038-41. DOI: 10.1074/jbc.272.4.2038. View

15.

Vento R, DAlessandro N, Giuliano M, Lauricella M, Carabillo M, Tesoriere G . Induction of apoptosis by arachidonic acid in human retinoblastoma Y79 cells: involvement of oxidative stress. Exp Eye Res. 2000; 70(4):503-17. DOI: 10.1006/exer.1998.0810. View

16.

Michalek H, Fortuna S, Pintor A . Age-related differences in brain choline acetyltransferase, cholinesterases and muscarinic receptor sites in two strains of rats. Neurobiol Aging. 1989; 10(2):143-8. DOI: 10.1016/0197-4580(89)90023-7. View

17.

Bruce G, Hersh L . The phosphorylation of choline acetyltransferase. Neurochem Res. 1989; 14(7):613-20. DOI: 10.1007/BF00964869. View

18.

Waller S, London E . Choline acetyltransferase activity and muscarinic binding in brain regions of aging fischer-344 rats. Neurochem Int. 2010; 14(4):483-90. DOI: 10.1016/0197-0186(89)90040-5. View

19.

Ogawa N, Asanuma M, Kondo Y, Nishibayashi S, Mori A . Reduced choline acetyltransferase activity and muscarinic M1 receptor levels in aged Fisher 344 rat brains did not parallel their respective mRNA levels. Brain Res. 1994; 658(1-2):87-92. DOI: 10.1016/s0006-8993(09)90013-0. View

20.

Strong R, Hicks P, Hsu L, Bartus R, Enna S . Age-related alterations in the rodent brain cholinergic system and behavior. Neurobiol Aging. 1980; 1(1):59-63. DOI: 10.1016/0197-4580(80)90025-1. View