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Activation of mGluR1 Mediates C1q-Dependent Microglial Phagocytosis of Glutamatergic Synapses in Alzheimer's Rodent Models
- Source :
- Mol Neurobiol
- Publication Year :
- 2018
-
Abstract
- Microglia and complements appear to be involved in the synaptic and cognitive deficits in Alzheimer's disease (AD), though the mechanisms remain elusive. In this study, utilizing two types of rodent model of AD, we reported increased complement C1q-mediated microglial phagocytosis of hippocampal glutamatergic synapses, which led to synaptic and cognitive deficits. We also found increased activity of the metabotropic glutamate receptor 1 (mGluR1) in hippocampal CA1 in the modeled rodents. Artificial activation of mGluR1 signaling promoted dephosphorylation of fragile X mental retardation protein (FMRP) and facilitated the local translation machinery of synaptic C1q mRNA, thus mimicking the C1q-mediated microglial phagocytosis of hippocampal glutamatergic synapses and synaptic and cognitive deficiency in the modeled rodents. However, suppression of mGluR1 signaling inhibited the dephosphorylation of FMRP and repressed the local translation of synaptic C1q mRNA, which consequently alleviated microglial phagocytosis of synapses and restored the synaptic and cognitive function in the rodent models. These findings illustrate a novel molecular mechanism underlying C1q-mediated microglial phagocytosis of hippocampal glutamatergic synapses in AD.
- Subjects :
- 0301 basic medicine
Male
Amyloid
Phagocytosis
Neuroscience (miscellaneous)
Mice, Transgenic
Hippocampal formation
Biology
Receptors, Metabotropic Glutamate
Hippocampus
Article
Dephosphorylation
Rats, Sprague-Dawley
03 medical and health sciences
Cellular and Molecular Neuroscience
Glutamatergic
0302 clinical medicine
Glutamates
Alzheimer Disease
medicine
Animals
Humans
RNA, Messenger
Microglia
Complement C1q
Translation (biology)
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Neurology
Metabotropic glutamate receptor
Protein Biosynthesis
Synapses
Metabotropic glutamate receptor 1
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15591182
- Volume :
- 56
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Molecular neurobiology
- Accession number :
- edsair.doi.dedup.....44f8bab2973fbf118155745050f9dd70