Hippocampal infusions of apolipoprotein E peptides induce long-lasting cognitive impairment.
The inheritance of the varepsilon4 allele of apolipoprotein E (ApoE4) and cholinergic system dysfunction have long been associated with the pathology of Alzheimer's disease (AD). Recently, in vitro studies have established a direct link between ApoE and cholinergic function in that synthetic peptides containing segments of the ApoE protein (ApoE(133-149) and ApoE(141-148)) interact with alpha7 nicotinic acetylcholine receptors (nAChRs) in the hippocampus. This raises the possibility that ApoE peptides may contribute to cognitive impairment in AD in that the hippocampus plays a key role in cognitive functioning. To test this, we acutely infused ApoE peptides into the ventral hippocampus of female Sprague-Dawley rats and assessed the resultant effects on radial-arm maze choice accuracy over a period of weeks after the infusion. Local ventral hippocampal infusion of ApoE peptides caused significant cognitive impairment in radial-arm maze learning that persisted several weeks after the acute infusion. This persisting deficit may be an important model for understanding the relationship between ApoE protein-induced neurotoxicity and cognitive impairment as well as serve as a platform for the development of new therapies to avoid neurotoxicity and cognitive decline.
Eddins
Donnie
D
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, United States.
Klein
Rebecca C
RC
Yakel
Jerrel L
JL
Levin
Edward D
ED
D000818:Animals; D001057:Apolipoproteins E / Q000008:administration & dosage / Q000378:metabolism*; D002404:Catheterization; D002755:Choice Behavior / Q000502:physiology; D003072:Cognition Disorders / Q000503:physiopathology*; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D018782:Maze Learning / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time
D001057:Apolipoproteins E; D010446:Peptide Fragments