Deregulated Local Protein Synthesis in the Brain Synaptosomes of a Mouse Model for Alzheimer’s Disease
While protein synthesis in neurons is largely attributed to cell body and dendrites, the capability of synaptic regions to synthesize new proteins independently of the cell body has been widely demonstrated as an advantageous mechanism subserving synaptic plasticity. Thus, the contribution that local protein synthesis at synapses makes to physiology and pathology of brain plasticity may be more prevalent than initially thought. In this study, we tested if local protein synthesis at synapses is deregulated in the brains of TgCRND8 mice, an animal model for Alzheimer’s disease (AD) overexpressing mutant human amyloid precursor protein (APP). To this end, we used synaptosomes as a model system to study the functionality of the synaptic regions in mouse brains. Our results showed that, while TgCRND8 mice exhibit early signs of brain inflammation and deficits in learning, the electrophoretic profile of newly synthesized proteins in their synaptosomes was subtly different from that of the control mice. Interestingly, APP itself was, in part, locally synthesized in the synaptosomes, underscoring the potential importance of local translation at synapses. More importantly, after the contextual fear conditioning, de novo synthesis of some individual proteins was significantly enhanced in the synaptosomes of control animals, but the TgCRND8 mice failed to display such synaptic modulation by training. Taken together, our results demonstrate that synaptic synthesis of proteins is impaired in the brain of a mouse model for AD, and raise the possibility that this deregulation may contribute to the early progression of the pathology.
KeywordsLocal protein synthesis Synaptosomes Amyloid precursor protein Alzheimer’s disease Synaptic plasticity Learning
The authors are grateful to Prof. Rita Santamaria from the Department of Pharmacy, University of Naples Federico II, for genotyping the mice and to Dr. Roberta Scognamiglio, Dr. Aurora Bracale, Dr. Fabiana Alfieri, and Dr. Ornella Smith from the Department of Biology, University of Naples Federico II, for technical assistance.
This work was supported by “Finanziamento Ricerca di Ateneo” from University of Naples Federico II and by POR Campania FESR 2014/2020 from Regione Campania (Project N. B61G18000470007).
Compliance with Ethical Standards
This research involves animals that were treated in strict accordance with the Institutional Guidelines complying with the Italian D.L. no. 116 of January 27, 1992 of Ministero della Salute and with the associated guidelines by the European Communities Council (2010/63/EU). The experimental protocols reported herein have been approved by the Institutional Animal Care and Use Committee (CSV) of University of Naples Federico II (377/2015-PR, 15/05/2015).
Conflict of Interest
The authors declare that they have no conflict of interest.
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