Neuropsychiatric Disorders

In addition to developmental disorders, altered translational control appears to be involved in behavioral abnormalities associated with neuropsychiatric disorders. We recently have conducted studies investigating how aberrant translational control is involved in schizophrenia and have been identifying translational control mechanisms involved in the response of mice to antipsychotic drugs.

 

  First video shows successful navigation of a Morris Water Maze (MWM) by WT mice. The mouse was trained to find the submerged platform (red cirle) and then the platform position was changed (white circle). Second video shows the failure to learn new platform position of a PERK conditional knock-out mice. For recent selected examples of our work on this topic, please see: Trinh, M.A., Kaphzan, H., Wek, R.C., Pierre, P., Cavener, D.R., and Klann, E. (2012) Brain- specific disruption of the eIF2a kinase PERK decreases ATF4 expression and impairs behavioral flexibility. Cell Rep., in press. Valjent, E., Bertan-Gonzalez, J., Bowling, H., Lopez, S., Santini, E., Herve, D., Greengard, P., Hoeffer, C.A., Klann, E., Girault, J.-A., and Fisone, G. (2011) Haloperidol regulates the state of phosphorylation of ribosomal protein S6 in the striatum via activation of PKA and phosphorylation of DARPP-32. Neuropsychopharmacology, in press. Santini, E. and Klann, E. (2011) Dysregulated mTORC1-dependent translational control: from brain disorders to psychoactive drugs. Front. Behav. Neurosci. 5: 76.