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Gene-environment interaction between lead and Apolipoprotein E4 causes cognitive behavior deficits in mice

Overview of attention for article published in Molecular Neurodegeneration, February 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (83rd percentile)
  • Average Attention Score compared to outputs of the same age and source

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Title
Gene-environment interaction between lead and Apolipoprotein E4 causes cognitive behavior deficits in mice
Published in
Molecular Neurodegeneration, February 2017
DOI 10.1186/s13024-017-0155-2
Pubmed ID
Authors

Anna K. Engstrom, Jessica M. Snyder, Nobuyo Maeda, Zhengui Xia

Abstract

Alzheimer's disease (AD) is characterized by progressive cognitive decline and memory loss. Environmental factors and gene-environment interactions (GXE) may increase AD risk, accelerate cognitive decline, and impair learning and memory. However, there is currently little direct evidence supporting this hypothesis. In this study, we assessed for a GXE between lead and ApoE4 on cognitive behavior using transgenic knock-in (KI) mice that express the human Apolipoprotein E4 allele (ApoE4-KI) or Apolipoprotein E3 allele (ApoE3-KI). We exposed 8-week-old male and female ApoE3-KI and ApoE4-KI mice to 0.2% lead acetate via drinking water for 12 weeks and assessed for cognitive behavior deficits during and after the lead exposure. In addition, we exposed a second (cellular) cohort of animals to lead and assessed for changes in adult hippocampal neurogenesis as a potential underlying mechanism for lead-induced learning and memory deficits. In the behavior cohort, we found that lead reduced contextual fear memory in all animals; however, this decrease was greatest and statistically significant only in lead-treated ApoE4-KI females. Similarly, only lead-treated ApoE4-KI females exhibited a significant decrease in spontaneous alternation in the T-maze. Furthermore, all lead-treated animals developed persistent spatial working memory deficits in the novel object location test, and this deficit manifested earlier in ApoE4-KI mice, with female ApoE4-KI mice exhibiting the earliest deficit onset. In the cellular cohort, we observed that the maturation, differentiation, and dendritic development of adult-born neurons in the hippocampus was selectively impaired in lead-treated female ApoE4-KI mice. These data suggest that GXE between ApoE4 and lead exposure may contribute to cognitive impairment and that impaired adult hippocampal neurogenesis may contribute to these deficits in cognitive behavior. Together, these data suggest a role for GXE and sex differences in AD risk.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 50 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 8 16%
Student > Ph. D. Student 8 16%
Student > Doctoral Student 6 12%
Student > Bachelor 4 8%
Researcher 3 6%
Other 4 8%
Unknown 17 34%
Readers by discipline Count As %
Medicine and Dentistry 8 16%
Agricultural and Biological Sciences 6 12%
Environmental Science 4 8%
Psychology 4 8%
Neuroscience 4 8%
Other 7 14%
Unknown 17 34%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 February 2017.
All research outputs
#3,143,172
of 22,952,268 outputs
Outputs from Molecular Neurodegeneration
#452
of 852 outputs
Outputs of similar age
#68,193
of 420,202 outputs
Outputs of similar age from Molecular Neurodegeneration
#14
of 27 outputs
Altmetric has tracked 22,952,268 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 852 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.3. This one is in the 43rd percentile – i.e., 43% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 420,202 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 83% of its contemporaries.
We're also able to compare this research output to 27 others from the same source and published within six weeks on either side of this one. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.