Annual Meeting of the Society for Neuroscience edition:36 location:Atlanta, GA, U.S.A. date:October 14-18, 2006
The goal of the present study was to investigate changes in protein expression at the level of neurotransmission in the prefrontal cortex in a neurodevelopmental model of schizophrenia. We investigated protein fractions enriched in plasma membranes and vesicles, obtained from the prefrontal cortex (PFC) of adult neonatal ventral hippocampal lesioned (nVHL) rats and sham littermates, applying an organelle proteomic analysis. Postpubertal nVHL rats show several behavioral features associated with schizophrenia and are therefore extensively used to study schizophrenia-linked behaviors [Lipska et al., Neuropsychopharm 1993; Flores et al, J. Neurosci, 1996; Laplante et al., J Neurochem 2004; Lipska, J Psych Neurosci 2004]. Proteins present in significantly different spots on two-dimensional protein patterns of ultracentrifugated PFC samples were identified using MALDI and nano-ESI-Q-TOF mass spectrometric analysis and database searching. The organelle proteomic approach applied here allowed the identification of several proteins of low abundance that previously had not been linked to schizophrenia-associated behaviors. Seven identified dysregulated proteins are known to play roles in plasma membrane receptor expression and/or neurotransmitter release. Results of the present organelle proteomic study support the hypothesis that neurotransmission in the PFC may be dysregulated as a consequence of hippocampal lesions in the nVHL model. The observation of altered expression of these signal transduction-modulating proteins, as well as proteins in other organelles [Vercauteren et al., Eur J Pharmacol 2004; Yates et al., Nat Rev Mol Cell Biol 2005] may contribute to further unraveling of molecular mechanisms underlying schizophrenia-linked behaviors.