Synaptic proteome perturbations after maternal immune activation: Identification of embryonic and adult hippocampal changes.

Autor: Yotova AY; Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany; Goethe University Frankfurt, Faculty of Biological Sciences, Institute of Cell Biology and Neuroscience, Frankfurt, Germany., Li LL; Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Turku Brain and Mind Center, University of Turku and Åbo Akademi University, 20014 Turku, Finland., O'Leary A; Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany; Department of Neuropsychopharmacology, Institute of Chemistry, University of Tartu, Tartu, Estonia., Tegeder I; Goethe University Frankfurt, Faculty of Medicine, Institute of Clinical Pharmacology, Frankfurt, Germany., Reif A; Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany., Courtney MJ; Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Turku Brain and Mind Center, University of Turku and Åbo Akademi University, 20014 Turku, Finland., Slattery DA; Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany., Freudenberg F; Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany; Goethe University Frankfurt, Faculty of Biological Sciences, Institute of Cell Biology and Neuroscience, Frankfurt, Germany. Electronic address: freudenberg@em.uni-frankfurt.de.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2024 Oct; Vol. 121, pp. 351-364. Date of Electronic Publication: 2024 Jul 31.
DOI: 10.1016/j.bbi.2024.07.040
Abstrakt: Background: Maternal immune activation (MIA) triggers neurobiological changes in offspring, potentially reshaping the molecular synaptic landscape, with the hippocampus being particularly vulnerable. However, critical details regarding developmental timing of these changes and whether they differ between males and females remain unclear.
Methods: We induced MIA in C57BL/6J mice on gestational day nine using the viral mimetic poly(I:C) and performed mass spectrometry-based proteomic analyses on hippocampal synaptoneurosomes of embryonic (E18) and adult (20 ± 1 weeks) MIA offspring.
Results: In the embryonic synaptoneurosomes, MIA led to lipid, polysaccharide, and glycoprotein metabolism pathway disruptions. In the adult synaptic proteome, we observed a dynamic shift toward transmembrane trafficking, intracellular signalling cascades, including cell death and growth, and cytoskeletal organisation. In adults, many associated pathways overlapped between males and females. However, we found distinct sex-specific enrichment of dopaminergic and glutamatergic pathways. We identified 50 proteins altered by MIA in both embryonic and adult samples (28 with the same directionality), mainly involved in presynaptic structure and synaptic vesicle function. We probed human phenome-wide association study data in the cognitive and psychiatric domains, and 49 of the 50 genes encoding these proteins were significantly associated with the investigated phenotypes.
Conclusions: Our data emphasise the dynamic effects of viral-like MIA on developing and mature hippocampi and provide novel targets for study following prenatal immune challenges. The 22 proteins that changed directionality from the embryonic to adult hippocampus, suggestive of compensatory over-adaptions, are particularly attractive for future investigations.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andreas Reif has received honoraria for lectures and/or advisory board activity from Janssen, Boehringer Ingelheim, COMPASS, SAGE/Biogen, LivaNova, Medice, Shire/Takeda, MSD and cyclerion and received grant support from Medice and Janssen. None of these relationships are directly related to the study reported herein. All other authors report no financial relationships with commercial interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: