Mice heterozygous for an inactivated allele of the schizophrenia associated Brd1 gene display selective cognitive deficits with translational relevance to schizophrenia.
Schizophrenia is a debilitating brain disorder characterized by disturbances of emotion, perception and cognition. Cognitive impairments predict functional outcome in schizophrenia and are detectable even in the prodromal stage of the disorder. However, our understanding of the underlying neurobiology is limited and procognitive treatments remain elusive. We recently demonstrated that mice heterozygous for an inactivated allele of the schizophrenia-associated Brd1 gene (Brd1+/-mice) display behaviors reminiscent of schizophrenia, including impaired social cognition and long-term memory. Here, we further characterize performance of these mice by following the preclinical guidelines recommended by the 'Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)' and 'Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS)' initiatives to maximize translational value. Brd1+/-mice exhibit relational encoding deficits, compromised working and long term memory, as well as impaired executive cognitive functioning with cognitive behaviors relying on medial prefrontal cortex being particularly affected. Akin to patients with schizophrenia, the cognitive deficits displayed by Brd1+/-mice are not global, but selective. Our results underline the value of Brd1+/-mice as a promising tool for studying the neurobiology of cognitive deficits in schizophrenia.
Department of Biomedicine, Aarhus University, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark; H. Lundbeck A/S, Synaptic Transmission, Valby, Denmark.
Per
P
Qvist
Department of Biomedicine, Aarhus University, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark; Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, & Neuroscience, King's College London, London, UK.
Anto P
AP
Rajkumar
H. Lundbeck A/S, Synaptic Transmission, Valby, Denmark.
John P
JP
Redrobe
Department of Biomedicine, Aarhus University, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark.
Mette
M
Nyegaard
Department of Biomedicine, Aarhus University, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark.
Jane H
JH
Christensen
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark; Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
Ole
O
Mors
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark.
Gregers
G
Wegener
H. Lundbeck A/S, Synaptic Transmission, Valby, Denmark.
Michael
M
Didriksen
Department of Biomedicine, Aarhus University, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark. Electronic address: ANDERS@BIOMED.AU.DK.
Anders D
AD
Børglum
D000483:Alleles; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D056344:Executive Function / Q000502:physiology*; D006579:Heterozygote; D051548:Histone Acetyltransferases / Q000235:genetics*; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D017397:Prefrontal Cortex / Q000503:physiopathology; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D000092468:Bromodomain Containing Proteins
D051548:Histone Acetyltransferases; C562256:BRD1 protein, mouse; D000092468:Bromodomain Containing Proteins
Bromodomain-Containing 1; Cognition; Cognitive flexibility; Deletion 22q13; Executive functions; Long-term memory; Mice; Working memory