Leveraging genetic diversity in mice to inform individual differences in brain microstructure and memory

被引:1
|
作者
Murdy, Thomas J. [1 ]
Dunn, Amy R. [1 ]
Singh, Surjeet [1 ]
Telpoukhovskaia, Maria A. [1 ]
Zhang, Shanrong [1 ]
White, Jacqueline K. [1 ]
Kahn, Itamar [2 ]
Febo, Marcelo [3 ]
Kaczorowski, Catherine C. [1 ]
机构
[1] Jackson Lab, Bar Harbor, ME 04609 USA
[2] Columbia Univ, Zuckerman Mind Brain Behav Inst, Dept Neurosci, New York, NY USA
[3] Univ Florida, Dept Neurosci, Coll Med, Gainesville, FL USA
来源
关键词
Alzheimer's disease; brain reserve; genetic diversity; 5XFAD; memory; NODDI; DTI; diffusion MRI (dMRI); NEURITE ORIENTATION DISPERSION; ALZHEIMERS-DISEASE; DIFFUSION TENSOR; COGNITIVE FUNCTION; MOUSE MODEL; NEURONS; ABNORMALITIES; HIPPOCAMPUS; PATHOLOGY; AMYGDALA;
D O I
10.3389/fnbeh.2022.1033975
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
In human Alzheimer's disease (AD) patients and AD mouse models, both differential pre-disease brain features and differential disease-associated memory decline are observed, suggesting that certain neurological features may protect against AD-related cognitive decline. The combination of these features is known as brain reserve, and understanding the genetic underpinnings of brain reserve may advance AD treatment in genetically diverse human populations. One potential source of brain reserve is brain microstructure, which is genetically influenced and can be measured with diffusion MRI (dMRI). To investigate variation of dMRI metrics in pre-disease-onset, genetically diverse AD mouse models, we utilized a population of genetically distinct AD mice produced by crossing the 5XFAD transgenic mouse model of AD to 3 inbred strains (C57BL/6J, DBA/2J, FVB/NJ) and two wild-derived strains (CAST/EiJ, WSB/EiJ). At 3 months of age, these mice underwent diffusion magnetic resonance imaging (dMRI) to probe neural microanatomy in 83 regions of interest (ROIs). At 5 months of age, these mice underwent contextual fear conditioning (CFC). Strain had a significant effect on dMRI measures in most ROIs tested, while far fewer effects of sex, sex*strain interactions, or strain*sex*5XFAD genotype interactions were observed. A main effect of 5XFAD genotype was observed in only 1 ROI, suggesting that the 5XFAD transgene does not strongly disrupt neural development or microstructure of mice in early adulthood. Strain also explained the most variance in mouse baseline motor activity and long-term fear memory. Additionally, significant effects of sex and strain*sex interaction were observed on baseline motor activity, and significant strain*sex and sex*5XFAD genotype interactions were observed on long-term memory. We are the first to study the genetic influences of brain microanatomy in genetically diverse AD mice. Thus, we demonstrated that strain is the primary factor influencing brain microstructure in young adult AD mice and that neural development and early adult microstructure are not strongly altered by the 5XFAD transgene. We also demonstrated that strain, sex, and 5XFAD genotype interact to influence memory in genetically diverse adult mice. Our results support the usefulness of the 5XFAD mouse model and convey strong relationships between natural genetic variation, brain microstructure, and memory.
引用
收藏
页数:25
相关论文
共 50 条
  • [31] Individual Differences in Learning Rate and Fear Response Predict Fear Memory and Recovery in Mice and Human Subjects
    Yan Gao
    Wei Li
    Bo Sui
    Nashat Abumaria
    Neuroscience Bulletin, 2020, 36 : 815 - 820
  • [32] Individual differences in spatial working memory strategies differentially reflected in the engagement of control and default brain networks
    Suljic, Nina Purg
    Kraljic, Aleksij
    Rahmati, Masih
    Cho, Youngsun T.
    Ozimic, Anka Slana
    Murray, John D.
    Anticevic, Alan
    Repovs, Grega
    CEREBRAL CORTEX, 2024, 34 (08)
  • [33] Variations in working memory capacity predict individual differences in general learning abilities among genetically diverse mice
    Kolata, S
    Light, K
    Townsend, DA
    Hale, G
    Grossman, HC
    Matzel, LD
    NEUROBIOLOGY OF LEARNING AND MEMORY, 2005, 84 (03) : 241 - 246
  • [34] AH LOCUS - BIOCHEMICAL BASIS FOR GENETIC-DIFFERENCES IN BRAIN-TUMOR FORMATION IN MICE
    LEVITT, RC
    FYSH, JM
    JENSEN, NM
    NEBERT, DW
    GENETICS, 1979, 92 (04) : 1205 - 1210
  • [35] Carrying the past to the future: Distinct brain networks underlie individual differences in human spatial working memory capacity
    Liu, Siwei
    Poh, Jia-Hou
    Koh, Hui Li
    Ng, Kwun Kei
    Loke, Yng Miin
    Lim, Joseph Kai Wei
    Chong, Joanna Su Xian
    Zhou, Juan
    NEUROIMAGE, 2018, 176 : 1 - 10
  • [36] Genetic differences in response to novelty and spatial memory using a two-trial recognition task in mice
    Dellu, F
    Contarino, A
    Simon, H
    Koob, GF
    Gold, LH
    NEUROBIOLOGY OF LEARNING AND MEMORY, 2000, 73 (01) : 31 - 48
  • [37] Regional brain shrinkage over two years: Individual differences and effects of pro-inflammatory genetic polymorphisms
    Persson, N.
    Ghisletta, P.
    Dahle, C. L.
    Bender, A. R.
    Yang, Y.
    Yuan, P.
    Daugherty, A. M.
    Raz, N.
    NEUROIMAGE, 2014, 103 : 334 - 348
  • [38] Individual differences in working memory, nonverbal IQ and mathematics achievement and brain mechanisms associated with symbolic and nonsymbolic number processing
    Gullick, Margaret M.
    Sprute, Lisa A.
    Temple, Elise
    LEARNING AND INDIVIDUAL DIFFERENCES, 2011, 21 (06) : 644 - 654
  • [39] Individual Differences in Mental Rotational Ability, Brain Electrophysiology, and Task Performance Are Correlated in Males During Spatial Working Memory
    Christie, Gregory J.
    Saucier, Deborah M.
    CANADIAN JOURNAL OF EXPERIMENTAL PSYCHOLOGY-REVUE CANADIENNE DE PSYCHOLOGIE EXPERIMENTALE, 2012, 66 (04): : 292 - 292
  • [40] Morphine analgesia in male inbred genetic diversity mice recapitulates the among-individual variance in response to morphine in humans
    Yin Yang
    Bowen Guan
    Qiang Wei
    Wei Wang
    Aimin Meng
    Animal Models and Experimental Medicine, 2022, 5 (03) : 288 - 296