The maternal immune activation model uncovers a role for the Arx gene in GABAergic dysfunction in schizophrenia
Jay P Nakamura, Anna Schroeder, Matthew Hudson, Nigel Jones, Brendan Gillespie, Xin Du, Michael Notaras, Vaidy Swaminathan, William R Reay, Joshua R Atkins, Melissa J Green, Vaughan J Carr, Murray J Cairns, Suresh Sundram, Rachel A Hill
Brain Behavior and Immunity | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2019
A hallmark feature of schizophrenia is altered high frequency neural oscillations, including reduced auditory-evoked gamma oscillatory power, which is underpinned by parvalbumin (PV) interneuron dysfunction. Maternal immune activation (MIA) in rodents models an environmental risk factor for schizophrenia and recapitulates these PV interneuron changes. This study sought to link reduced PV expression in the MIA model with alterations to auditory-evoked gamma oscillations and transcript expression. We further aligned transcriptional findings from the animal model with human genome sequencing data. We show that MIA, induced by the viral mimetic, poly-I:C in C57Bl/6 mice, caused in adult offsprin..View full abstract
Awarded by NHMRC
This study was supported by a NARSAD Young Investigator Award to R.A.H. and a Monash University internal grant. R.A.H. is supported by a National Health and Medical Research Council Career Development (RD. Wright) Fellowship. J.P.N. is supported by an Australian Rotary Health scholarship. M.N. is supported by an NHMRC CJ Martin fellowship. X.D. is supported by an NHMRC/ARC dementia fellowship. N.J. is supported by an Australian Research Council Future fellowship. The behavioural neuroscience laboratory are supported by 'One in Five', philanthropic organization. Data obtained from the Australia Schizophrenia Research Bank are supported by a NSW Health Sydney Genomics Collaborative Grants Program (2015). Translational genomics for schizophrenia: Using whole genome sequencing to define the network architecture for personalized interventions. CIs: Cairns MJ, Green MJ, Carr VC. $800,000, as well as NHMRC project grant (grant number APP1051673). The Authors have declared that there are no conflicts of interest in relation to the subject of this study.