| 1 | J. Neurosci. 2010 Apr 30: 6025-35 |
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| PMID | 20427661 |
| Title | Canonical TGF-beta signaling is required for the balance of excitatory/inhibitory transmission within the hippocampus and prepulse inhibition of acoustic startle. |
| Abstract | SMAD4 is a unique nuclear transducer for all TGF-beta signaling pathways and regulates gene transcription during development and tissue homeostasis. To elucidate the postnatal role of TGF-beta signaling in the mammalian brain, we generated forebrain-specific SMAD4 knock-out mice. Surprisingly, the mutants showed no alteration in long-term potentiation and water maze, suggesting that SMAD4 is not required for spatial learning and memory. However, these mutant mice did show enhancement of paired-pulse facilitation in excitatory synaptic transmission and stronger paired-pulse depression of GABA(A) currents in the hippocampus. The alteration of hippocampal electrophysiology correlated with mouse hyperactivity in homecage and open field tests. Mutant mice also showed overgrooming as well as deficits of prepulse inhibition, a widely used endophenotype of schizophrenia. With a specific real-time PCR array focused on TGF-beta signaling pathway, we identified a novel regulation mechanism of the pathway in the hippocampal neurons, in which SMAD4-mediated signaling suppresses the level of extracellular antagonism of TGF-beta ligands through transcriptional regulation of follistatin, a selective inhibitor to activin/TGF-beta signaling in the hippocampus. In summary, we suggest that the canonical TGF-beta signaling pathway is critical for use-dependent modulation of GABA(A) synaptic transmission and dendritic homeostasis; furthermore, a disruption in the balance of the excitatory and inhibitory hippocampal network can result in psychiatric-like behavior. |
| SCZ Keywords | schizophrenia |
| 2 | Asia Pac Psychiatry 2015 Sep 7: 268-75 |
| PMID | 25504777 |
| Title | Pilot study for family-based association analysis of schizophrenia in a Korean population: Analysis for candidate genes positionally on chromosome 18q21. |
| Abstract | schizophrenia is the most devastating mental illness that causes severe deterioration in social and occupational functioning. This is a pilot study for family-based association analysis of schizophrenia in a Korean population to search candidate genes functionally relevant and positionally on chromosome 18. We have recruited 27 probands (with psychosis) with their parents and siblings whenever possible. We analyzed 20 SNPs (Single Nucleotide Polymorphism) of seven neuronal genes in chromosome 18 for DNA samples that was checked for the data quality and genotype error. For testing of association, we performed family-based association tests analyses with each individual SNP, using the phenotype of psychosis. And then, we performed family-based association tests haplotype analyses with each individual SNP, using the phenotype of psychosis. Finally, we performed linkage disequilibrium analyses for the phenotype of schizophrenia. We found one significant SNPs of one neuronal gene in chromosome 18 (P value?SMAD4 genes (rs8096092, rs2298617) were in strong linkage disequilibrium with each other (D'?>?0.60). The present findings provide convergent evidence (fine mapping of a chromosomal locus 18q21 associated with schizophrenia) suggesting that a specific MAPK4 could be a candidate gene for causing a spectrum of schizophrenia phenotype. |
| SCZ Keywords | schizophrenia |