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Partial genetic deletion of neuregulin 1 modulates the effects of stress on sensorimotor gating, dendritic morphology, and HPA axis activity in adolescent mice.
Schizophr Bull. 2014 Nov; 40(6):1272-84.SB

Abstract

Stress has been linked to the pathogenesis of schizophrenia. Genetic variation in neuregulin 1 (NRG1) increases the risk of developing schizophrenia and may help predict which high-risk individuals will transition to psychosis. NRG1 also modulates sensorimotor gating, a schizophrenia endophenotype. We used an animal model to demonstrate that partial genetic deletion of Nrg1 interacts with stress to promote neurobehavioral deficits of relevance to schizophrenia. Nrg1 heterozygous (HET) mice displayed greater acute stress-induced anxiety-related behavior than wild-type (WT) mice. Repeated stress in adolescence disrupted the normal development of higher prepulse inhibition of startle selectively in Nrg1 HET mice but not in WT mice. Further, repeated stress increased dendritic spine density in pyramidal neurons of the medial prefrontal cortex (mPFC) selectively in Nrg1 HET mice. Partial genetic deletion of Nrg1 also modulated the adaptive response of the hypothalamic-pituitary-adrenal axis to repeated stress, with Nrg1 HET displaying a reduced repeated stress-induced level of plasma corticosterone than WT mice. Our results demonstrate that Nrg1 confers vulnerability to repeated stress-induced sensorimotor gating deficits, dendritic spine growth in the mPFC, and an abberant endocrine response in adolescence.

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Authors+Show Affiliations

Chohan TW
The Brain and Mind Research Institute, University of Sydney, Sydney, NSW 2006, Australia; Discipline of Pharmacology, School of Medical Science, University of Sydney, Sydney, NSW 2006, Australia;
Boucher AA
The Brain and Mind Research Institute, University of Sydney, Sydney, NSW 2006, Australia;
Spencer JR
The Brain and Mind Research Institute, University of Sydney, Sydney, NSW 2006, Australia; Discipline of Pharmacology, School of Medical Science, University of Sydney, Sydney, NSW 2006, Australia;
Kassem MS
The Brain and Mind Research Institute, University of Sydney, Sydney, NSW 2006, Australia;
Hamdi AA
Discipline of Pharmacology, School of Medical Science, University of Sydney, Sydney, NSW 2006, Australia;
Karl T
Neuroscience Research Australia, Randwick, NSW 2031, Australia.
Fok SY
The Brain and Mind Research Institute, University of Sydney, Sydney, NSW 2006, Australia;
Bennett MR
The Brain and Mind Research Institute, University of Sydney, Sydney, NSW 2006, Australia;
Arnold JC
The Brain and Mind Research Institute, University of Sydney, Sydney, NSW 2006, Australia; Discipline of Pharmacology, School of Medical Science, University of Sydney, Sydney, NSW 2006, Australia; jonathon.arnold@sydney.edu.au.

MeSH

AnimalsDendritic SpinesDisease Models, AnimalFemaleHypothalamo-Hypophyseal SystemMaleMiceMice, Inbred C57BLNeuregulin-1Pituitary-Adrenal SystemPrefrontal CortexPrepulse InhibitionSensory GatingStress, Psychological

Pub Type(s)

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

Language

eng

PubMed ID

24442851

Citation

Chohan, Tariq W., et al. "Partial Genetic Deletion of Neuregulin 1 Modulates the Effects of Stress On Sensorimotor Gating, Dendritic Morphology, and HPA Axis Activity in Adolescent Mice." Schizophrenia Bulletin, vol. 40, no. 6, 2014, pp. 1272-84.
Chohan TW, Boucher AA, Spencer JR, et al. Partial genetic deletion of neuregulin 1 modulates the effects of stress on sensorimotor gating, dendritic morphology, and HPA axis activity in adolescent mice. Schizophr Bull. 2014;40(6):1272-84.
Chohan, T. W., Boucher, A. A., Spencer, J. R., Kassem, M. S., Hamdi, A. A., Karl, T., Fok, S. Y., Bennett, M. R., & Arnold, J. C. (2014). Partial genetic deletion of neuregulin 1 modulates the effects of stress on sensorimotor gating, dendritic morphology, and HPA axis activity in adolescent mice. Schizophrenia Bulletin, 40(6), 1272-84. https://doi.org/10.1093/schbul/sbt193
Chohan TW, et al. Partial Genetic Deletion of Neuregulin 1 Modulates the Effects of Stress On Sensorimotor Gating, Dendritic Morphology, and HPA Axis Activity in Adolescent Mice. Schizophr Bull. 2014;40(6):1272-84. PubMed PMID: 24442851.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Partial genetic deletion of neuregulin 1 modulates the effects of stress on sensorimotor gating, dendritic morphology, and HPA axis activity in adolescent mice. AU - Chohan,Tariq W, AU - Boucher,Aurelie A, AU - Spencer,Jarrah R, AU - Kassem,Mustafa S, AU - Hamdi,Areeg A, AU - Karl,Tim, AU - Fok,Sandra Y, AU - Bennett,Maxwell R, AU - Arnold,Jonathon C, Y1 - 2014/01/17/ PY - 2014/1/21/entrez PY - 2014/1/21/pubmed PY - 2015/6/20/medline KW - PPI KW - adolescence KW - dendritic morphology KW - neuregulin 1 KW - schizophrenia KW - stress SP - 1272 EP - 84 JF - Schizophrenia bulletin JO - Schizophr Bull VL - 40 IS - 6 N2 - Stress has been linked to the pathogenesis of schizophrenia. Genetic variation in neuregulin 1 (NRG1) increases the risk of developing schizophrenia and may help predict which high-risk individuals will transition to psychosis. NRG1 also modulates sensorimotor gating, a schizophrenia endophenotype. We used an animal model to demonstrate that partial genetic deletion of Nrg1 interacts with stress to promote neurobehavioral deficits of relevance to schizophrenia. Nrg1 heterozygous (HET) mice displayed greater acute stress-induced anxiety-related behavior than wild-type (WT) mice. Repeated stress in adolescence disrupted the normal development of higher prepulse inhibition of startle selectively in Nrg1 HET mice but not in WT mice. Further, repeated stress increased dendritic spine density in pyramidal neurons of the medial prefrontal cortex (mPFC) selectively in Nrg1 HET mice. Partial genetic deletion of Nrg1 also modulated the adaptive response of the hypothalamic-pituitary-adrenal axis to repeated stress, with Nrg1 HET displaying a reduced repeated stress-induced level of plasma corticosterone than WT mice. Our results demonstrate that Nrg1 confers vulnerability to repeated stress-induced sensorimotor gating deficits, dendritic spine growth in the mPFC, and an abberant endocrine response in adolescence. SN - 1745-1701 UR - https://www.unboundmedicine.com/medline/citation/24442851/Partial_genetic_deletion_of_neuregulin_1_modulates_the_effects_of_stress_on_sensorimotor_gating_dendritic_morphology_and_HPA_axis_activity_in_adolescent_mice_ DB - PRIME DP - Unbound Medicine ER -