Proteomic Analysis of Brain Region and Sex-Specific Synaptic Protein Expression in the Adult Mouse Brain

Cells - Tập 9 Số 2 - Trang 313
Ute Distler1,2,3, Sven Schumann4, Hans-Georg Kesseler4, Rainer Pielot5,6, Karl‐Heinz Smalla6, Malte Sielaff2,3, Michael J. Schmeißer1,7,6, Stefan Tenzer2,3
1Focus Program Translational Neurosciences (FTN), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany
2Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany
3Research Center for Immunotherapy (FZI), University Medical Center, Johannes Gutenberg-University Mainz, 55131 Mainz, Germany
4Institute of Anatomy, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany;
5Institute for Pharmacology and Toxicology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
6Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany
7Institute for Microscopic Anatomy and Neurobiology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany

Tóm tắt

Genetic disruption of synaptic proteins results in a whole variety of human neuropsychiatric disorders including intellectual disability, schizophrenia or autism spectrum disorder (ASD). In a wide range of these so-called synaptopathies a sex bias in prevalence and clinical course has been reported. Using an unbiased proteomic approach, we analyzed the proteome at the interaction site of the pre- and postsynaptic compartment, in the prefrontal cortex, hippocampus, striatum and cerebellum of male and female adult C57BL/6J mice. We were able to reveal a specific repertoire of synaptic proteins in different brain areas as it has been implied before. Additionally, we found a region-specific set of novel synaptic proteins differentially expressed between male and female individuals including the strong ASD candidates DDX3X, KMT2C, MYH10 and SET. Being the first comprehensive analysis of brain region-specific synaptic proteomes from male and female mice, our study provides crucial information on sex-specific differences in the molecular anatomy of the synapse. Our efforts should serve as a neurobiological framework to better understand the influence of sex on synapse biology in both health and disease.

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