Mice heterozygous for an inactivated allele of the schizophrenia associated Brd1 gene display selective cognitive deficits with translational relevance to schizophrenia

TY - JOUR

T1 - Mice heterozygous for an inactivated allele of the schizophrenia associated Brd1 gene display selective cognitive deficits with translational relevance to schizophrenia

AU - Qvist, Per

AU - Rajkumar, Anto P.

AU - Redrobe, John P.

AU - Nyegaard, Mette

AU - Christensen, Jane H.

AU - Mors, Ole

AU - Wegener, Gregers

AU - Didriksen, Michael

AU - Børglum, Anders D.

PY - 2017/5

Y1 - 2017/5

N2 - 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.

AB - 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.

KW - Mice

KW - cognition

KW - Bromodomain-Containing 1

KW - working memory

KW - long-term memory

KW - executive functions

KW - Cognitive flexibility

KW - Deletion 22q13

U2 - 10.1016/j.nlm.2017.03.009

DO - 10.1016/j.nlm.2017.03.009

M3 - Article

SN - 1074-7427

VL - 141

SP - 44

EP - 52

JO - Neurobiology of learning and memory

JF - Neurobiology of learning and memory

ER -