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Identifier

000414963

Title

Comparative proteomic analysis of the MAM mouse model of schizophrenia

Alternative Title

Πρωτεωμική ανάλυση σε εγκεφαλικό ιστό μυών που αποτελούν μοντέλο σχιζοτυπικής συμπεριφοράς

Author

Κυριαζίδης, Ευάγγελος Π.

Thesis advisor

Σιδηροπούλου, Κυριακή

Reviewer

Αϊβαλιώτης, Μιχάλης
Αλεξανδράκη, Δέσποινα

Abstract

Schizophrenia constitutes a chronic neuropsychiatric disorder, in the group of psychotic disorders, estimated to affect 1% of the world's population. Although the causal biological basis of the disease remains largely undetermined, variations in gene and protein expression, possibly in early developmental stages of the nervous system, have been presented as an important aspect of its pathogenesis. The proteomic characterization of neurodevelopmental models of schizophrenia, in this regard, comprises an intriguing direction towards understanding its neurobiological basis and the molecular effects of abnormal/perturbed neuronal development and aberrant synaptic physiology, in general. The present work focuses on a comparative mass spectrometry based proteomic analysis between the “prenatal MAM” (methylazoxymethanol acetate - exposed) mouse model of schizophrenia (induced at embryonic day 16) and saline animals with an emphasis on gender variations. In this respect, protein extracts of a distinct brain region, namely the prefrontal cortex, were fractionated by one dimensional SDS-PAGE into multiple protein fractions that were separately analyzed by mass spectrometry-based bottom-up proteomics and specialized bioinformatics, involving identification and relative protein quantitation. Significantly enriched and underrepresented proteins and pathways (over control animals) were determined for each gender as a means to characterize the animal model, in protein level. Substantial differences were observed between male and female MAM-treated animals illustrating a differential response to the gestational MAM administration. A prominent upregulation of various metabolic proteins in MAM-exposed males established a case for a functionally perturbed prefrontal cortex, suggesting a more intense “schizotypal” phenotype in males compared to MAM-treated females. These observations may provide an early framework towards investigating potential mechanistic molecular correlations with the human condition while highlighting the importance of incorporating gender into translational neuropsychiatric research.

Language

English

Subject

Methylazxyomethanol acetate

Proteomics

Schizophrenia models

Μοντέλα σχιζοφρένειας

Σχιζοφρένεια

Issue date

2018-03-23

Collection

School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses