Disrupted-in-Schizophrenia 1 (DISC1) Overexpression and Juvenile Immune Activation Cause Sex-Specific Schizophrenia-Related Psychopathology in Rats

Journal article


Publication Details

Author(s): Uzuneser T, Speidel J, Kogias G, Wang AL, Silva MADS, Huston JP, Zoicas I, von Hörsten S, Kornhuber J, Korth C, Müller CP
Journal: Frontiers in Psychiatry
Publication year: 2019
Volume: 10
ISSN: 1664-0640


Abstract

Synaptic pruning is a critical refinement step during neurodevelopment, and schizophrenia has been associated with overpruning of cortical dendritic spines. Both human studies and animal models implicate disrupted-in-schizophrenia 1 (DISC1) gene as a strong susceptibility factor for schizophrenia. Accumulating evidence supports the involvement of DISC1 protein in the modulation of synaptic elimination during critical periods of neurodevelopment and of dopamine D2-receptor-mediated signaling during adulthood. In many species, synaptic pruning occurs during juvenile and adolescent periods and is mediated by microglia, which can be over-activated by an immune challenge, giving rise to overpruning. Therefore, we sought to investigate possible interactions between a transgenic DISC1 model (tgDISC1) and juvenile immune activation (JIA) by the bacterial cell wall endotoxin lipopolysaccharide on the induction of schizophrenia-related behavioral and neurochemical disruptions in adult female and male rats. We examined possible behavioral aberrations along three major symptom dimensions of schizophrenia including psychosis, social and emotional disruptions, and cognitive impairments. We detected significant gene environment interactions in the amphetamine-induced locomotion in female animals and in the amphetamine-induced anxiety in male animals. Surprisingly, gene environment interactions improved social memory in both male and female animals. JIA alone disrupted spatial memory and recognition memory, but only in male animals. DISC1 overexpression alone induced an improvement in sensorimotor gating, but only in female animals. Our neurochemical analyses detected sex- and manipulation-dependent changes in the postmortem monoamine content of animals. Taken together, we here report sex-specific effects of environment and genotype as well as their interaction on behavioral phenotypes and neurochemical profiles relevant for schizophrenia.


FAU Authors / FAU Editors

Kogias, Georgios
Professur für Suchtmedizin
Kornhuber, Johannes Prof. Dr. med.
Lehrstuhl für Psychiatrie und Psychotherapie
Müller, Christian P. Prof. Dr.
Professur für Suchtmedizin
Uzuneser, Taygun
Professur für Suchtmedizin
von Hörsten, Stephan Prof. Dr.
Professur für Experimentelle Biomedizin


External institutions with authors

Heinrich-Heine-Universität Düsseldorf


How to cite

APA:
Uzuneser, T., Speidel, J., Kogias, G., Wang, A.-L., Silva, M.A.D.S., Huston, J.P.,... Müller, C.P. (2019). Disrupted-in-Schizophrenia 1 (DISC1) Overexpression and Juvenile Immune Activation Cause Sex-Specific Schizophrenia-Related Psychopathology in Rats. Frontiers in Psychiatry, 10. https://dx.doi.org/10.3389/fpsyt.2019.00222

MLA:
Uzuneser, Taygun, et al. "Disrupted-in-Schizophrenia 1 (DISC1) Overexpression and Juvenile Immune Activation Cause Sex-Specific Schizophrenia-Related Psychopathology in Rats." Frontiers in Psychiatry 10 (2019).

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Last updated on 2019-23-04 at 07:53