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Cognition in female transmembrane domain neuregulin 1 mutant mice.
Behav Brain Res. 2012 Jan 01; 226(1):218-23.BB

Abstract

Neuregulin 1 (Nrg1) has been implicated in the development of schizophrenia and influences key neurodevelopmental processes such as myelination and neuronal migration. The heterozygous transmembrane domain Nrg1 mutant mouse (Nrg1 TM HET) exhibits a sex-specific phenotype relevant for schizophrenia research, which is characterized by the development of locomotor hyperactivity, social withdrawal, and changes to the serotonergic system. Cognitive impairments are characteristic of schizophrenia patients and male Nrg1 TM HET mice exhibit cognitive deficits in novel object recognition and contextual fear conditioning. Thus, we investigated the cognitive performance of female Nrg1 mutants, using a cognitive test battery for a variety of paradigms, including fear conditioning, cheeseboard, Y maze, object exploration and passive avoidance. Female Nrg1 mutant mice displayed impairments in the fear conditioning tasks, including significantly reduced fear conditioning to a context and a strong trend towards a decreased ability for cue fear conditioning. These cognitive deficits were task-specific, as no differences were seen between mutant and control mice in spatial learning of the cheeseboard for reference memory measures, in the Y-maze for working memory measures, or in novel object recognition and passive avoidance paradigms. These findings indicate that neuregulin 1 plays only a minor role in cognition in female test mice. The current study provides a further behavioural validation of this genetic mouse model for the schizophrenia candidate gene neuregulin 1 and confirms the importance of considering female test animals in animal models for schizophrenia.

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Authors+Show Affiliations

Chesworth R
Neuroscience Research Australia, Randwick, NSW 2031, Australia; Schizophrenia Research Institute, Darlinghurst, NSW 2010, Australia.
Downey L
No affiliation info available
Logge W
No affiliation info available
Killcross S
No affiliation info available
Karl T
No affiliation info available

MeSH

AnimalsAvoidance LearningCognitionConditioning, ClassicalDisease Models, AnimalExploratory BehaviorFearFemaleMaze LearningMemory, Short-TermMiceNeuregulin-1Recognition, PsychologySchizophrenia

Pub Type(s)

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

Language

eng

PubMed ID

21944941

Citation

Chesworth, Rose, et al. "Cognition in Female Transmembrane Domain Neuregulin 1 Mutant Mice." Behavioural Brain Research, vol. 226, no. 1, 2012, pp. 218-23.
Chesworth R, Downey L, Logge W, et al. Cognition in female transmembrane domain neuregulin 1 mutant mice. Behav Brain Res. 2012;226(1):218-23.
Chesworth, R., Downey, L., Logge, W., Killcross, S., & Karl, T. (2012). Cognition in female transmembrane domain neuregulin 1 mutant mice. Behavioural Brain Research, 226(1), 218-23. https://doi.org/10.1016/j.bbr.2011.09.019
Chesworth R, et al. Cognition in Female Transmembrane Domain Neuregulin 1 Mutant Mice. Behav Brain Res. 2012 Jan 1;226(1):218-23. PubMed PMID: 21944941.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cognition in female transmembrane domain neuregulin 1 mutant mice. AU - Chesworth,Rose, AU - Downey,Laura, AU - Logge,Warren, AU - Killcross,Simon, AU - Karl,Tim, Y1 - 2011/09/16/ PY - 2011/08/10/received PY - 2011/09/07/revised PY - 2011/09/10/accepted PY - 2011/9/28/entrez PY - 2011/9/29/pubmed PY - 2012/2/10/medline SP - 218 EP - 23 JF - Behavioural brain research JO - Behav Brain Res VL - 226 IS - 1 N2 - Neuregulin 1 (Nrg1) has been implicated in the development of schizophrenia and influences key neurodevelopmental processes such as myelination and neuronal migration. The heterozygous transmembrane domain Nrg1 mutant mouse (Nrg1 TM HET) exhibits a sex-specific phenotype relevant for schizophrenia research, which is characterized by the development of locomotor hyperactivity, social withdrawal, and changes to the serotonergic system. Cognitive impairments are characteristic of schizophrenia patients and male Nrg1 TM HET mice exhibit cognitive deficits in novel object recognition and contextual fear conditioning. Thus, we investigated the cognitive performance of female Nrg1 mutants, using a cognitive test battery for a variety of paradigms, including fear conditioning, cheeseboard, Y maze, object exploration and passive avoidance. Female Nrg1 mutant mice displayed impairments in the fear conditioning tasks, including significantly reduced fear conditioning to a context and a strong trend towards a decreased ability for cue fear conditioning. These cognitive deficits were task-specific, as no differences were seen between mutant and control mice in spatial learning of the cheeseboard for reference memory measures, in the Y-maze for working memory measures, or in novel object recognition and passive avoidance paradigms. These findings indicate that neuregulin 1 plays only a minor role in cognition in female test mice. The current study provides a further behavioural validation of this genetic mouse model for the schizophrenia candidate gene neuregulin 1 and confirms the importance of considering female test animals in animal models for schizophrenia. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/21944941/Cognition_in_female_transmembrane_domain_neuregulin_1_mutant_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(11)00688-7 DB - PRIME DP - Unbound Medicine ER -