ApoE isoform-specific differences in behavior and cognition associated with subchronic MPTP exposure. Academic Article uri icon

Overview

abstract

  • Parkinson's disease (PD) is characterized clinically by progressive motor dysfunction; overt parkinsonism is often preceded by prodromal symptoms including disturbances in the sleep-wake cycle. Up to 80% of patients with PD also develop dementia. In humans, there are three major apolipoprotein E isoforms: E2, E3, and E4. Increased rate of dementia in PD may be associated with E4 isoform. To better understand prodromal changes associated with E4, we exposed young (3-5 mo) male and female mice expressing E3 or E4 via targeted replacement to a subchronic dosage of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We hypothesized that E4 mice would be more susceptible to MPTP-related behavioral and cognitive changes. MPTP-treated E4 mice explored novel objects longer than genotype-matched saline-treated mice. In contrast, saline-treated E3 mice preferentially explored the novel object whereas MPTP-treated E3 mice did not and showed impaired object recognition. MPTP treatment altered swim speed of E4, but not E3, mice in the water maze compared to controls. Thus, E4 carriage may influence the preclinical symptoms associated with PD. Increased efforts are warranted to study early time points in this disease model.

publication date

  • August 17, 2020

Research

keywords

  • Apolipoprotein E3
  • Apolipoprotein E4
  • Behavior, Animal
  • MPTP Poisoning
  • Motor Activity
  • Recognition, Psychology
  • Spatial Learning

Identity

PubMed Central ID

  • PMC7433653

Scopus Document Identifier

  • 85089769968

Digital Object Identifier (DOI)

  • 10.1038/s41401-018-0003-0

PubMed ID

  • 32817303

Additional Document Info

volume

  • 27

issue

  • 9