| First Author | Lipina TV | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 12 | Pages | e51562 |
| PubMed ID | 23272119 | Mgi Jnum | J:195647 |
| Mgi Id | MGI:5484970 | Doi | 10.1371/journal.pone.0051562 |
| Citation | Lipina TV, et al. (2012) Prophylactic valproic acid treatment prevents schizophrenia-related behaviour in Disc1-L100P mutant mice. PLoS One 7(12):e51562 |
| abstractText | BACKGROUND: Schizophrenia is a neurodevelopmental disorder with onset early in adulthood. Disrupted-In-Schizophrenia-1 (DISC1) is a susceptibility gene for schizophrenia and other psychiatric disorders. Disc1-L100P mutant mice show behaviors relevant to schizophrenia at 12 weeks, but not at 8 weeks of age, and may be useful for investigating the onset of schizophrenia in early adulthood. METHODS: We investigated whether early valproic acid treatment would prevent behavioral, cellular and gene expression abnormalities in Disc1-L100P mutants. RESULTS: Valproic acid prevented hyperactivity and deficits in prepulse inhibition and latent inhibition in Disc1-L100P mice. Genome-wide transcription profiling identified Lcn2 (lipocalin2) transcripts as being elevated by the Disc1 mutation and corrected by valproate. Disc1-L100P mice also had increased glial cell numbers in the subventricular zone, which was normalized by valproate. Genetic deletion of Lcn2 normalized glial cell numbers and behavior in Disc1-L100P mutants. CONCLUSIONS: Pharmacological treatments are a feasible way of preventing abnormal behaviour in a genetic model of schizophrenia. Lcn2 is a potential novel drug target for early intervention in schizophrenia. |
