The environmental contaminant benzo[a]pyrene (B[a]P) has been regarded as one of the pathogens of oral premalignant and malignant lesions. To elucidate the pathogenesis of oral premalignancies, B[a]P-induced dysplasia of the murine tongue was investigated for G1-associated cell cycle regulation. B[a]P solution was applied orally up to six weeks to induce epithelial dysplasia of the tongue. BrdU incorporation and the expression of p21, cyclin D1, and CDK4 were examined by immunohistochemistry and Western blotting. Rb phosphorylation and E2F-Rb binding were examined by immunoprecipitation and Western blotting. B[a]P treatment resulted in dysplastic changes and active DNA synthesis in the tongue epithelia. Immunohistochemical analyses showed p21 up-regulation and cyclin D1/CDK4 overexpression in B[a]P-induced dysplasia. Rb hyperphosphorylation and E2F release were caused by B[a]P treatment. Thus, dysregulation of G1-phase regulation is likely to be an important event in the development of oral epithelial dysplasia in mice.

Prepulse inhibition (PPI) is considered to be one of the most promising neurophysiological indexes for translational research in psychiatry. Impairment of PPI has been reported in several psychiatric diseases, particularly schizophrenia, where PPI is considered a candidate intermediate phenotype (endophenotype) of the disease. Recent findings from a variety of research areas have provided important evidence regarding PPI impairment. Human brain imaging studies have demonstrated the involvement of the striatum, hippocampus, thalamus and frontal and parietal cortical regions in PPI. In addition, several genetic polymorphisms, including variations in the genes coding for Catechol O-methyltransferase, Neuregulin 1, nuclear factor kappa-B subunit 3 and serotonin-2A receptor were related to PPI; and these findings support PPI as a polygenetic trait that involves several neurotransmitter pathways. Early psychosis studies suggest that PPI disruption is present before the onset of psychosis. Also, discrepancy of PPI impairment between children and adults can be found in other psychiatric diseases, such as autistic spectrum disorders and posttraumatic stress disorder, and comprehensive investigation of startle response might contribute to understand the impairment of the neural circuitry in psychiatric diseases. Finally, recent studies with both Asian and Caucasian subjects indicate that patients with schizophrenia exhibit impaired PPI, and impaired sensorimotor gating might be a global common psychophysiological feature of schizophrenia. In conclusion, studies of PPI have successfully contributed to a better understanding of the fundamental neural mechanisms underlying sensorimotor gating and will certainly be most valuable in devising future approaches that aim to investigate the complex pathogenesis of psychiatric diseases.
Adult ; Asian Continental Ancestry Group ; Catechol O-Methyltransferase ; Catechols ; Child ; Clinical Coding ; Endophenotypes ; Hippocampus ; Humans ; Mental Disorders ; Neuregulin-1 ; Neuroimaging ; Neurotransmitter Agents ; Phenotype ; Polymorphism, Genetic ; Psychophysiology ; Psychotic Disorders ; Schizophrenia ; Sensory Gating ; Startle Reaction ; Stress Disorders, Post-Traumatic ; Thalamus ; Translational Medical Research