Here is a summary of the page in bullet points:
- The page reports on a recent study led by researchers at Penn State that unveils a novel genetic-environmental interaction (G-E) model of schizophrenia using PCP-treated Kpna1 knockout (KO) mice¹.
- The study aims to illuminate the complex interplay between genetic predisposition and environmental factors in the onset of this devastating mental disorder¹.
- The study focuses on the Kpna1 gene, which encodes a protein crucial for the proper functioning of the brain’s neural circuitry. The researchers created Kpna1 KO mice, which lack this gene, and exposed them to PCP, a dissociative drug, during their adolescence¹.
- The subchronic exposure to PCP led to the emergence of schizophrenia-like symptoms in the mice, such as impaired cognitive function, disrupted social behavior, and heightened anxiety levels¹.
- The study reveals the molecular mechanisms underlying the G-E model, such as the dysregulation of synaptic plasticity, neuronal excitability, and neuroinflammation¹.
- The study also identifies potential biomarkers and therapeutic targets for schizophrenia, such as the NMDA receptor, the mTOR pathway, and the cytokine IL-6¹.
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Link to the scientific paper: A Kpna1-deficient psychotropic drug-induced schizophrenia model mouse for studying gene–environment interactions
KPNA1 is a mediator of nucleocytoplasmic transport that is abundantly expressed in the mammalian brain and regulates neuronal differentiation and synaptic function. De novo mutations in Kpna1 have been identified using genome-wide association studies in humans with schizophrenia; however, it remains unclear how KPNA1 contributes to schizophrenia pathogenesis. Recent studies have suggested a complex combination of genetic and environmental factors that are closely related to psychiatric disorders. Here, we found that subchronic administration of phencyclidine, a psychotropic drug, induced vulnerability and behavioral abnormalities consistent with the symptoms of schizophrenia in Kpna1 -deficient mice. Microarray assessment revealed that the expression levels of dopamine d1/d2 receptors, an RNA editing enzyme, and a cytoplasmic dynein component were significantly altered in the nucleus accumbens brain region in a gene-environment (G × E) interaction-dependent manner. Our findings demonstrate that Kpna1 -deficient mice may be useful as a G × E interaction mouse model for psychiatric disorders and for further investigation into the pathogenesis of such diseases and disorders.
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