An organelle proteomic method to study neurotransmission‐related proteins, applied to a neurodevelopmental model of schizophrenia

Abstract

Limited information is currently available on molecular events that underlie schizophrenia-like behaviors in animal models. Accordingly, we developed an organelle proteomic approach enabling the study of neurotransmission-related proteins in the prefrontal cortex (PFC) of postpubertal (postnatal day 60 (PD60)) neonatally ventral hippocampal (nVH) lesioned rats, an extensively used neurodevelopmental model of schizophrenia-like behaviors. The PFC was chosen because of its purported role in the etiology of the disease. Statistical analysis of 392 reproducible spots on 2-D organelle proteomic patterns revealed significant changes in intensity of 18 proteinous spots in plasma membrane-enriched fractions obtained from postpubertal nVH lesioned rats compared to controls. Mass spectrometric analysis and database searching allowed the identification of a single protein in each of the nine differential spots, including proteins of low abundance, such as neurocalcin delta. Most of the identified dysregulated proteins, including clathrin light chain B, syntaxin binding protein 1b and visinin-like protein 1 are known to be linked to various neurotransmitter systems and to play key roles in plasma membrane receptor expression and recycling as well as synaptic vesicle exocytosis/recycling. Organelle proteomic approaches have hence proved to be most useful to identify key proteins linked to a given behavior in animal models of brain diseases.

A Combined Metabonomic and Proteomic Approach Identifies Frontal Cortex Changes in a Chronic Phencyclidine Rat Model in Relation to Human Schizophrenia Brain Pathology

“…Previous post-mortem studies of brain tissue from SCZ patients and analyses of a ketamine-injected rodent model have shown a reduction in the numbers and staining intensity of VSNL1-positive pyramidal neurons (Bernstein et al, 2003;Bernstein et al, 2002). These results have been confirmed by microarray and proteomic studies (Miklos and Maleszka, 2004;Vercauteren et al, 2007). Consistent with the change in Orange boxes: altered pathways determined by in silico pathway analysis using the IPKB software.…”

Behaviour and prefrontal protein differences in C57BL/6N and 129 X1/SvJ mice

“…The standard global scale proteomic analysis applied does address potential protein differences in subcellular fractions such as mitochondria, nucleus or plasma membrane. Thus, false negative results are possible and future studies examining subcellular compartments, though challenging, would be useful to reduce false negative rates (Vercauteren et al, 2007).…”

Association of VSNL1 with schizophrenia, frontal cortical function, and biological significance for its gene product as a modulator of cAMP levels and neuronal morphology

“…21, 22, 23 These results have been confirmed independently by microarray and proteomic studies. 24, 25 More recently, increased expression of microRNAs (for example, miR-181b) was discovered in schizophrenia and was found to negatively regulate VILIP-1 expression in schizophrenic brains and in human dopaminergic SH-SY5Y neurons, 26 further adding to evidence implicating VILIP-1 in schizophrenia. Interestingly, insulin and IGF-1, which have also been associated with schizophrenia, increases the expression of genes that show pathological decrease in expression in schizophrenia, including VILIP-1 expression, in human SH-SY5Y model neurons.…”