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Behavioural effects of high fat diet exposure starting in late adolescence in neuregulin 1 transmembrane domain mutant mice.
Behav Brain Res. 2019 11 05; 373:112074.BB

Abstract

A limited number of studies suggest that poor diet choices may impact on the mental state of schizophrenia patients. Our own work found that high fat diet (HFD) reversed social recognition memory deficits in female mice mutant for the schizophrenia risk gene neuregulin 1 (i.e. Nrg1 transmembrane domain: Nrg1 TM HET). Sex effects are common in schizophrenia and adolescence is a period of increased sensitivity to environmental risk factors. Thus, we investigated whether adolescent HFD exposure modulates schizophrenia-relevant behaviours of male and female Nrg1 TM HET mice. Male and female Nrg1 TM HET and their control littermates were exposed to either HFD or a standard chow diet from late adolescence onwards. After 8 weeks, adult mice were tested for locomotion and exploration, social behaviours, sensorimotor gating (i.e. prepulse inhibition), and fear-associated learning and memory. Nrg1 TM HET mice exhibited hyper-locomotion and an anxiolytic-like phenotype across sex and Nrg1 males tended to show deficient fear-associated memory. HFD increased body weight over time in all mice, an effect less pronounced in Nrg1 female mice. The moderately suppressive effect of HFD on females' exploration was less evident in Nrg1 mutants. Nrg1 TM HET female mice also displayed a less pronounced increase in HFD-induced cue freezing and HFD modulated the response to the cue in a complex genotype-dependent manner. In conclusion, HFD exposure starting in late adolescence has sex-specific effects on exploration and fear-associated memory, which was less pronounced in females mutant for Nrg1. This suggests that research into the role of diets in schizophrenia-relevant domains should consider genetic risk factors for the disease as schizophrenia risk genes such as Nrg1 may modulate dietary effects.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Zieba J
Neuroscience Research Australia, Randwick, NSW 2031, Australia; School of Medical Sciences, UNSW Sydney, NSW 2052, Australia; Schizophrenia Research Institute, Randwick, NSW 2031, Australia.
Morris MJ
School of Medical Sciences, UNSW Sydney, NSW 2052, Australia.
Karl T
Neuroscience Research Australia, Randwick, NSW 2031, Australia; School of Medical Sciences, UNSW Sydney, NSW 2052, Australia; Schizophrenia Research Institute, Randwick, NSW 2031, Australia; School of Medicine, Western Sydney University, NSW 2560, Australia. Electronic address: t.karl@westernsydney.edu.au.

MeSH

AnimalsBehavior, AnimalDiet, High-FatDisease Models, AnimalExploratory BehaviorFearFemaleHeterozygoteLocomotionMaleMiceMice, Inbred C57BLMotor ActivityNeuregulin-1PhenotypePrepulse InhibitionSchizophreniaSensory GatingSex FactorsSocial Behavior

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31284014

Citation

Zieba, Jerzy, et al. "Behavioural Effects of High Fat Diet Exposure Starting in Late Adolescence in Neuregulin 1 Transmembrane Domain Mutant Mice." Behavioural Brain Research, vol. 373, 2019, p. 112074.
Zieba J, Morris MJ, Karl T. Behavioural effects of high fat diet exposure starting in late adolescence in neuregulin 1 transmembrane domain mutant mice. Behav Brain Res. 2019;373:112074.
Zieba, J., Morris, M. J., & Karl, T. (2019). Behavioural effects of high fat diet exposure starting in late adolescence in neuregulin 1 transmembrane domain mutant mice. Behavioural Brain Research, 373, 112074. https://doi.org/10.1016/j.bbr.2019.112074
Zieba J, Morris MJ, Karl T. Behavioural Effects of High Fat Diet Exposure Starting in Late Adolescence in Neuregulin 1 Transmembrane Domain Mutant Mice. Behav Brain Res. 2019 11 5;373:112074. PubMed PMID: 31284014.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Behavioural effects of high fat diet exposure starting in late adolescence in neuregulin 1 transmembrane domain mutant mice. AU - Zieba,Jerzy, AU - Morris,Margaret J, AU - Karl,Tim, Y1 - 2019/07/05/ PY - 2019/03/21/received PY - 2019/07/04/revised PY - 2019/07/05/accepted PY - 2019/7/10/pubmed PY - 2020/9/15/medline PY - 2019/7/9/entrez KW - Adolescence KW - Behaviour KW - High fat diet KW - Mouse KW - Neuregulin 1 KW - Sex effects KW - Transmembrane domain SP - 112074 EP - 112074 JF - Behavioural brain research JO - Behav Brain Res VL - 373 N2 - A limited number of studies suggest that poor diet choices may impact on the mental state of schizophrenia patients. Our own work found that high fat diet (HFD) reversed social recognition memory deficits in female mice mutant for the schizophrenia risk gene neuregulin 1 (i.e. Nrg1 transmembrane domain: Nrg1 TM HET). Sex effects are common in schizophrenia and adolescence is a period of increased sensitivity to environmental risk factors. Thus, we investigated whether adolescent HFD exposure modulates schizophrenia-relevant behaviours of male and female Nrg1 TM HET mice. Male and female Nrg1 TM HET and their control littermates were exposed to either HFD or a standard chow diet from late adolescence onwards. After 8 weeks, adult mice were tested for locomotion and exploration, social behaviours, sensorimotor gating (i.e. prepulse inhibition), and fear-associated learning and memory. Nrg1 TM HET mice exhibited hyper-locomotion and an anxiolytic-like phenotype across sex and Nrg1 males tended to show deficient fear-associated memory. HFD increased body weight over time in all mice, an effect less pronounced in Nrg1 female mice. The moderately suppressive effect of HFD on females' exploration was less evident in Nrg1 mutants. Nrg1 TM HET female mice also displayed a less pronounced increase in HFD-induced cue freezing and HFD modulated the response to the cue in a complex genotype-dependent manner. In conclusion, HFD exposure starting in late adolescence has sex-specific effects on exploration and fear-associated memory, which was less pronounced in females mutant for Nrg1. This suggests that research into the role of diets in schizophrenia-relevant domains should consider genetic risk factors for the disease as schizophrenia risk genes such as Nrg1 may modulate dietary effects. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/31284014/Behavioural_effects_of_high_fat_diet_exposure_starting_in_late_adolescence_in_neuregulin_1_transmembrane_domain_mutant_mice_ DB - PRIME DP - Unbound Medicine ER -