Tags

Type your tag names separated by a space and hit enter

Schizophrenia-relevant behaviours of female mice overexpressing neuregulin 1 type III.
Behav Brain Res. 2018 11 01; 353:227-235.BB

Abstract

Elevated levels of the type III (III) isoforms of neuregulin 1 (NRG1) have been observed in the brains of schizophrenia patients that carry NRG1 HapICE risk alleles, which is thought to contribute to the aetiology of the disease. We generated transgenic mice with forebrain driven Nrg1 III overexpression (Nrg1 III tg) and previously found that male heterozygous Nrg1 type III tg mice exhibit several schizophrenia-relevant behaviours including social and cognitive deficits as well as impaired sensorimotor gating. A number of mouse models for other Nrg1 isoform types exhibit sex-specific phenotypes yet sex-specific effects of Nrg1 III overexpression had not been evaluated. Thus, in this study we tested female Nrg1 III transgenic mice using a comprehensive behavioural phenotyping battery relevant to positive, negative and cognitive symptoms of schizophrenia. Firstly, forebrain Nrg1 III mRNA overexpression was confirmed in female transgenic mice using by qPCR. In the open field test, female Nrg1 III mice exhibited a blunted response to an acute challenge with the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801. Female Nrg1 III tg mice also exhibited moderately impaired short-term memory. Other behavioural domains including sensory abilities, motor functions, baseline locomotion, anxiety, sociability, social recognition memory, fear conditioning and prepulse inhibition were unperturbed in Nrg1 III tg females. Together these results illustrate that overexpressing forebrain Nrg1 III in female mice modifies the locomotive response to NMDA receptor antagonism without causing severe alterations to a number of other schizophrenia-related behavioural domains. The data suggest that behavioural effects of Nrg1 III overexpression may be sex-dependent.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Olaya JC
Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW 2031, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
Heusner CL
Astellas Research Institute of America LLC, Skokie, IL, USA.
Matsumoto M
Astellas Research Institute of America LLC, Skokie, IL, USA.
Shannon Weickert C
Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW 2031, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
Karl T
Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW 2031, Australia; School of Medicine, Western Sydney University, Campbelltown, NSW, Australia. Electronic address: t.karl@westernsydney.edu.au.

MeSH

AnimalsBrainDisease Models, AnimalExploratory BehaviorFemaleMemory, Short-TermMice, TransgenicMotor ActivityNeuregulin-1RNA, MessengerReceptors, N-Methyl-D-AspartateSchizophreniaSchizophrenic PsychologySensory GatingSex CharacteristicsSocial Behavior

Pub Type(s)

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

Language

eng

PubMed ID

29559337

Citation

Olaya, Juan C., et al. "Schizophrenia-relevant Behaviours of Female Mice Overexpressing Neuregulin 1 Type III." Behavioural Brain Research, vol. 353, 2018, pp. 227-235.
Olaya JC, Heusner CL, Matsumoto M, et al. Schizophrenia-relevant behaviours of female mice overexpressing neuregulin 1 type III. Behav Brain Res. 2018;353:227-235.
Olaya, J. C., Heusner, C. L., Matsumoto, M., Shannon Weickert, C., & Karl, T. (2018). Schizophrenia-relevant behaviours of female mice overexpressing neuregulin 1 type III. Behavioural Brain Research, 353, 227-235. https://doi.org/10.1016/j.bbr.2018.03.026
Olaya JC, et al. Schizophrenia-relevant Behaviours of Female Mice Overexpressing Neuregulin 1 Type III. Behav Brain Res. 2018 11 1;353:227-235. PubMed PMID: 29559337.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Schizophrenia-relevant behaviours of female mice overexpressing neuregulin 1 type III. AU - Olaya,Juan C, AU - Heusner,Carrie L, AU - Matsumoto,Mitsuyuki, AU - Shannon Weickert,Cynthia, AU - Karl,Tim, Y1 - 2018/03/17/ PY - 2017/08/21/received PY - 2018/03/15/revised PY - 2018/03/15/accepted PY - 2018/3/22/pubmed PY - 2018/11/27/medline PY - 2018/3/22/entrez KW - Behaviour KW - Female KW - Mouse model KW - Neuregulin 1 type III KW - Schizophrenia KW - Sex specificity SP - 227 EP - 235 JF - Behavioural brain research JO - Behav Brain Res VL - 353 N2 - Elevated levels of the type III (III) isoforms of neuregulin 1 (NRG1) have been observed in the brains of schizophrenia patients that carry NRG1 HapICE risk alleles, which is thought to contribute to the aetiology of the disease. We generated transgenic mice with forebrain driven Nrg1 III overexpression (Nrg1 III tg) and previously found that male heterozygous Nrg1 type III tg mice exhibit several schizophrenia-relevant behaviours including social and cognitive deficits as well as impaired sensorimotor gating. A number of mouse models for other Nrg1 isoform types exhibit sex-specific phenotypes yet sex-specific effects of Nrg1 III overexpression had not been evaluated. Thus, in this study we tested female Nrg1 III transgenic mice using a comprehensive behavioural phenotyping battery relevant to positive, negative and cognitive symptoms of schizophrenia. Firstly, forebrain Nrg1 III mRNA overexpression was confirmed in female transgenic mice using by qPCR. In the open field test, female Nrg1 III mice exhibited a blunted response to an acute challenge with the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801. Female Nrg1 III tg mice also exhibited moderately impaired short-term memory. Other behavioural domains including sensory abilities, motor functions, baseline locomotion, anxiety, sociability, social recognition memory, fear conditioning and prepulse inhibition were unperturbed in Nrg1 III tg females. Together these results illustrate that overexpressing forebrain Nrg1 III in female mice modifies the locomotive response to NMDA receptor antagonism without causing severe alterations to a number of other schizophrenia-related behavioural domains. The data suggest that behavioural effects of Nrg1 III overexpression may be sex-dependent. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/29559337/Schizophrenia_relevant_behaviours_of_female_mice_overexpressing_neuregulin_1_type_III_ DB - PRIME DP - Unbound Medicine ER -