ArticleTranslational psychiatry2013
Role of disrupted in schizophrenia 1 (DISC1) in stress-induced prefrontal cognitive dysfunction.
Article in Translational psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Targeting endoplasmic reticulum stress and protein misfolding in schizophrenia: the emerging promise of sigma-1 receptor agonists.Psychopharmacology · 2026Review
- Forward and reverse genomic screens enhance the understanding of phenotypic variation in a large Chinese rhesus macaque cohort.Nature communications · 2025Article
- Unusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia.Biological psychiatry · 2022Review
- The genie in the bottle-magnified calcium signaling in dorsolateral prefrontal cortex.Molecular psychiatry · 2021Review
- Adolescent psychosocial stress enhances sensitization to cocaine exposure in genetically vulnerable mice.Neuroscience research · 2020Article
- Expression of Behavioral Phenotypes in Genetic and Environmental Mouse Models of Schizophrenia.Frontiers in behavioral neuroscience · 2020Article
- Proteomics and bioinformatics analyses identify novel cellular roles outside mitochondrial function for human miro GTPases.Molecular and cellular biochemistry · 2019Article
- Unique Molecular Regulation of Higher-Order Prefrontal Cortical Circuits: Insights into the Neurobiology of Schizophrenia.ACS chemical neuroscience · 2018Review
- Proteostasis and Mitochondrial Role on Psychiatric and Neurodegenerative Disorders: Current Perspectives.Neural plasticity · 2018Review
- mGluR2/3 mechanisms in primate dorsolateral prefrontal cortex: evidence for both presynaptic and postsynaptic actions.Molecular psychiatry · 2017Article
- A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development.Oncotarget · 2017Article
- Gender-Specific Associations between CHGB Genetic Variants and Schizophrenia in a Korean Population.Yonsei medical journal · 2017Article
- The Role of Genes, Stress, and Dopamine in the Development of Schizophrenia.Biological psychiatry · 2017Review
- Caveolin-1 regulation of disrupted-in-schizophrenia-1 as a potential therapeutic target for schizophrenia.Journal of neurophysiology · 2017Article
- Epigenetic profiling of human brain differential DNA methylation networks in schizophrenia.BMC medical genomics · 2016Article
- Physiological approaches to understanding molecular actions on dorsolateral prefrontal cortical neurons underlying higher cognitive processing.Dong wu xue yan jiu = Zoological research · 2015Review
- Stress weakens prefrontal networks: molecular insults to higher cognition.Nature neuroscience · 2015Review
- Disrupted-in-Schizophrenia-1 SNPs and Susceptibility to Schizophrenia: Evidence from Malaysia.Psychiatry investigation · 2015Article
- Neurodevelopment, GABA system dysfunction, and schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Review
- Disrupted in schizophrenia 1 modulates medial prefrontal cortex pyramidal neuron activity through cAMP regulation of transient receptor potential C and small-conductance K+ channels.Biological psychiatry · 2014Article
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
Recent genetic studies have linked mental illness to alterations in disrupted in schizophrenia 1 (DISC1), a multifunctional scaffolding protein that regulates cyclic adenosine monophosphate (cAMP) signaling via interactions with phosphodiesterase 4 (PDE4). High levels of cAMP during stress exposure impair function of the prefrontal cortex (PFC), a region gravely afflicted in mental illness. As stress can aggravate mental illness, genetic insults to DISC1 may worsen symptoms by increasing cAMP levels. The current study examined whether viral knockdown (KD) of the Disc1 gene in rat PFC increases susceptibility to stress-induced PFC dysfunction. Rats were trained in a spatial working memory task before receiving infusions of (a) an active viral construct that knocked down Disc1 in PFC (DISC1 KD group), (b) a 'scrambled' construct that had no effect on Disc1 (Scrambled group), or (c) an active construct that reduced DISC1 expression dorsal to PFC (Anatomical Control group). Data were compared with an unoperated Control group. Cognitive performance was assessed following mild restraint stress that had no effect on normal animals. DISC1 KD rats were impaired by 1 h restraint stress, whereas Scrambled, Control, and Anatomical Control groups were unaffected. Thus, knocking down Disc1 in PFC reduced the threshold for stress-induced cognitive dysfunction, possibly through disinhibited cAMP signaling at neuronal network synapses. These findings may explain why patients with DISC1 mutations may be especially vulnerable to the effects of stress.
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