TY - JOUR
T1 - Deregulated Local Protein Synthesis in the Brain Synaptosomes of a Mouse Model for Alzheimer's Disease
AU - Cefaliello, Carolina
AU - Penna, Eduardo
AU - Barbato, Carmela
AU - Di Ruberto, Giuseppina
AU - Mollica, Maria Pina
AU - Trinchese, Giovanna
AU - Cigliano, Luisa
AU - Borsello, Tiziana
AU - Chun, Jong Tai
AU - Giuditta, Antonio
AU - Perrone-Capano, Carla
AU - Miniaci, Maria Concetta
AU - Crispino, Marianna
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
KW - Alzheimer Disease/metabolism
KW - Amyloid beta-Peptides/metabolism
KW - Amyloid beta-Protein Precursor/metabolism
KW - Animals
KW - Brain/metabolism
KW - Disease Models, Animal
KW - Memory Disorders/metabolism
KW - Mice, Transgenic
KW - Neurons/metabolism
KW - Plaque, Amyloid/pathology
KW - Synapses/metabolism
KW - Synaptosomes/metabolism
U2 - 10.1007/s12035-019-01835-y
DO - 10.1007/s12035-019-01835-y
M3 - Article
C2 - 31784883
VL - 57
SP - 1529
EP - 1541
JO - Molecular Neurobiology
JF - Molecular Neurobiology
SN - 0893-7648
IS - 3
ER -