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Brain Behav Immun. 2016 Aug;56:289-309. doi: 10.1016/j.bbi.2016.04.002. Epub 2016 Apr 4.

Widespread alterations in the synaptic proteome of the adolescent cerebral cortex following prenatal immune activation in rats.

Author information

1
Laboratory of Proteomics, Institute of Biology, Eötvös Loránd University, Budapest H-1117, Hungary; MTA-ELTE NAP B Neuroimmunology Research Group, Department of Biochemistry, Institute of Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
2
MTA-TTK NAP B MS Neuroproteomics Group, Hungarian Academy of Sciences, Budapest H-1117, Hungary; Department of Pediatrics, Medical University of Vienna, Vienna A-1090, Austria.
3
Laboratory of Proteomics, Institute of Biology, Eötvös Loránd University, Budapest H-1117, Hungary; MTA-ELTE NAP B Laboratory of Molecular and Systems Neurobiology, Institute of Biology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest H-1117, Hungary.
4
Laboratory of Proteomics, Institute of Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
5
Department of Anatomy, Cell and Developmental Biology, Institute of Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
6
MTA-TTK NAP B MS Neuroproteomics Group, Hungarian Academy of Sciences, Budapest H-1117, Hungary.
7
CRU Hungary Kft., Miskolc H-3529, Hungary.
8
Department of Pediatrics, Medical University of Vienna, Vienna A-1090, Austria.
9
MTA-ELTE NAP B Laboratory of Molecular and Systems Neurobiology, Institute of Biology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest H-1117, Hungary.
10
MTA-ELTE NAP B Neuroimmunology Research Group, Department of Biochemistry, Institute of Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
11
Laboratory of Proteomics, Institute of Biology, Eötvös Loránd University, Budapest H-1117, Hungary; MTA-TTK NAP B MS Neuroproteomics Group, Hungarian Academy of Sciences, Budapest H-1117, Hungary.
12
Laboratory of Proteomics, Institute of Biology, Eötvös Loránd University, Budapest H-1117, Hungary; Department of Physiology and Neurobiology, Institute of Biology, Eötvös Loránd University, Budapest H-1117, Hungary. Electronic address: kakekesi@ttk.elte.hu.

Abstract

An increasing number of studies have revealed associations between pre- and perinatal immune activation and the development of schizophrenia and autism spectrum disorders (ASDs). Accordingly, neuroimmune crosstalk has a considerably large impact on brain development during early ontogenesis. While a plethora of heterogeneous abnormalities have already been described in established maternal immune activation (MIA) rodent and primate animal models, which highly correlate to those found in human diseases, the underlying molecular background remains obscure. In the current study, we describe the long-term effects of MIA on the neocortical pre- and postsynaptic proteome of adolescent rat offspring in detail. Molecular differences were revealed in sub-synaptic fractions, which were first thoroughly characterized using independent methods. The widespread proteomic examination of cortical samples from offspring exposed to maternal lipopolysaccharide administration at embryonic day 13.5 was conducted via combinations of different gel-based proteomic techniques and tandem mass spectrometry. Our experimentally validated proteomic data revealed more pre- than postsynaptic protein level changes in the offspring. The results propose the relevance of altered synaptic vesicle recycling, cytoskeletal structure and energy metabolism in the presynaptic region in addition to alterations in vesicle trafficking, the cytoskeleton and signal transduction in the postsynaptic compartment in MIA offspring. Differing levels of the prominent signaling regulator molecule calcium/calmodulin-dependent protein kinase II in the postsynapse was validated and identified specifically in the prefrontal cortex. Finally, several potential common molecular regulators of these altered proteins, which are already known to be implicated in schizophrenia and ASD, were identified and assessed. In summary, unexpectedly widespread changes in the synaptic molecular machinery in MIA rats were demonstrated which might underlie the pathological cortical functions that are characteristic of schizophrenia and ASD.

KEYWORDS:

Autism spectrum disorder (ASD); Cerebral cortex; Maternal immune activation (MIA); Neuroproteomics; Schizophrenia; Synaptosome

PMID:
27058163
DOI:
10.1016/j.bbi.2016.04.002
[Indexed for MEDLINE]

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