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Ethologically based behavioural and neurochemical characterisation of mice with isoform-specific loss of dysbindin-1A in the context of schizophrenia. | LitMetric

Ethologically based behavioural and neurochemical characterisation of mice with isoform-specific loss of dysbindin-1A in the context of schizophrenia.

Neurosci Lett

School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland; Jiangsu Key Laboratory of Translational Research & Therapy for Neuro-Psychiatric Disorders and Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.

Published: September 2020

AI Article Synopsis

  • Dysbindin-1A knockout (Dys-1A KO) mice exhibit notable deficits in working memory and changes in behavior, including increased exploratory activity and social interaction compared to wildtype mice.
  • The study measured monoamine levels in various brain regions, finding reduced serotonin (5-HT) levels relative to its metabolite in the prefrontal cortex of Dys-1A KO mice.
  • Overall, these findings highlight the behavioral and neurochemical impacts of Dys-1A KO, indicating differences in exploration and serotonin activity that may be linked to schizophrenia symptoms.

Article Abstract

Dysbindin-1 is implicated in several aspects of schizophrenia, including cognition and both glutamatergic and dopaminergic neurotransmission. Targeted knockout of dysbindin-1A (Dys-1A KO), the most abundant and widely expressed isoform in the brain, is associated with deficits in delay/interference-dependent working memory. Using an ethologically based approach, the following behavioural phenotypes were examined in Dys-1A KO mice: exploratory activity, social interaction, anxiety and problem-solving ability. Levels of monoamines and their metabolites were measured in striatum, hippocampus and prefrontal cortex using high-performance liquid chromatography with electrochemical detection. The ethogram of initial exploration in Dys-1A KO mice was characterised by increased rearing from a seated position; over subsequent habituation, stillness was decreased relative to wildtype. In a test of dyadic social interaction with an unfamiliar conspecific in a novel environment, female KO mice showed an increase in investigative social behaviours. Marble burying behaviour was unchanged. Using the puzzle-box test to measure general problem-solving performance, no effect of genotype was observed across nine trials of increasing complexity. Dys-1A KO demonstrated lower levels of 5-HT in ratio to its metabolite 5-HIAA in the prefrontal cortex. These studies elaborate the behavioural and neurochemical phenotype of Dys-1A KO mice, revealing subtle genotype-related differences in non-social and social exploratory behaviours and habituation of exploration in a novel environment, as well as changes in 5-HT activity in brain areas related to schizophrenia.

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Source
http://dx.doi.org/10.1016/j.neulet.2020.135218DOI Listing

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