Human Apolipoprotein E Genotype Differentially Affects Olfactory Behavior and Sensory Physiology in Mice. (1st June 2018)

• Record Type: Journal Article
• Authors: East, Brett S.; Fleming, Gloria; Peng, Kathy; Olofsson, Jonas K.; Levy, Efrat; Mathews, Paul M.; Wilson, Donald A.
• Is Part Of: Neuroscience. Volume 380(2018)
• Page Start: 103
• Page End: 110
• Publication Date: 2018-06-01
• Subjects: AD Alzheimer's disease -- aPCX anterior piriform cortex -- ApoE apolipoprotein E -- FFT Fast-Fourier Transform -- LFP local field potential -- NKI The Nathan S. Kline Institute for Psychiatric Research -- OB olfactory bulb -- PCX piriform cortex; olfaction -- apolipoprotein E -- piriform cortex -- olfactory bulb -- Alzheimer's disease -- odor habituation; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.04.009
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: ApoE genotype does not affect initial odor investigation. ApoE genotype modulates behavioral odor habituation. ApoE genotype produces an ApoE4 > ApoE3 > ApoE2 excitability ranking. Deleterious effects of ApoE4 may be due to induced olfactory hyperexcitability. Protective effects of ApoE2 may be due to induced olfactory hypoexcitability. Abstract: Apolipoprotein E (ApoE) is an important lipid carrier in both the periphery and the brain. The ApoE ε4 allele (ApoE4) is the single most important genetic risk-factor for Alzheimer's disease (AD) while the ε2 allele (ApoE2) is associated with a lower risk of AD-related neurodegeneration compared to the most common variant, ε3 (ApoE3). ApoE genotype affects a variety of neural circuits; however, the olfactory system appears to provide early biomarkers of ApoE genotype effects. Here, we directly compared olfactory behavior and olfactory system physiology across all three ApoE genotypes in 6-month- and 12-month-old mice with targeted replacement for the human ApoE2, ApoE3, or ApoE4 genes. Odor investigation and habituation were assessed, along with, olfactory bulb and piriform cortical local field potential activity. The results demonstrate that while initial odor investigation was unaffected by ApoE genotype, odor habituation was impaired in E4 relative to E2 mice, with E3 mice intermediate in function. There was also significant deterioration of odor habituation from 6 to 12 months of age regardless of the ApoE genotype. Olfactory system excitability and odor responsiveness were similarly determined by ApoE genotype, with an ApoE4 > ApoE3 > ApoE2 excitability ranking. Although motivated behavior is influenced by many processes, hyper-excitability of ApoE4 mice may contribute to impaired odor habituation, while hypo-excitability of ApoE2 mice may contribute to its protective effects. Given that these ApoE mice do not have AD pathology, our results demonstrate how ApoE affects the olfactory system at early stages, prior to the development of AD.