Memory deficits and cholinergic impairments in apolipoprotein E-deficient mice.
Apolipoprotein E-deficient mice provide a useful system for studying the role of apolipoprotein E (apoE) in the function of distinct neuronal systems. In the present study we focused on the cholinergic system of these mice. This was pursued by measurements of specific biochemical, physiological and cognitive parameters. Morris Water Maze tasks revealed impairments in working memory but not in reference memory of the apoE-deficient mice. Measurements of brain choline acetyltransferase activities revealed them to be markedly lower in the hippocampus and frontal cortex of the apoE-deficient mice than in the corresponding brain areas of the controls, but unaltered in other brain areas. In addition, hypothermia induced by the centrally acting muscarinic agonist, oxotremorine, was reduced in the apoE-deficient mice as compared to controls. These results show that apoE-deficient mice have cholinergic deficits and highlight the importance of this mouse model for studying the interactions between apoE and the cholinergic nervous system.
Gordon
I
I
Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel.
Grauer
E
E
Genis
I
I
Sehayek
E
E
Michaelson
D M
DM
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001342:Autonomic Nervous System Diseases / Q000378:metabolism* / Q000523:psychology; D001921:Brain / Q000201:enzymology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000378:metabolism / Q000523:psychology; D005625:Frontal Lobe / Q000201:enzymology; D006624:Hippocampus / Q000201:enzymology; D007036:Hypothermia, Induced; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism* / Q000523:psychology; D051379:Mice; D018345:Mice, Knockout; D018721:Muscarinic Agonists / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000201:enzymology / Q000378:metabolism*
D001057:Apolipoproteins E; D018721:Muscarinic Agonists; D010095:Oxotremorine; D002795:Choline O-Acetyltransferase