title: Ultrastructure of microglia-synapse interactions in the HIV-1 Tat-injected murine central nervous system.
abstract: The destruction of normal synaptic architecture is the main pathogenetic substrate in HIV-associated neurocognitive disorder (HAND), but the sequence of cellular events underlying this outcome is not completely understood. Our recent work in a mouse model of HAND using a single intraparenchymal injection of the HIV-1 regulatory protein trans-activator of transcription revealed increased microglial phagocytosis that was accompanied by an increased release of pro-inflammatory cytokines and elimination of dendritic spines in vivo, thus suggesting that microglia-synapse interactions could be dysregulated in HAND. Here, we further examine the relationships between microglia and synaptic structures in our mouse model, at high spatial resolution using immunocytochemical electron microscopy. Our ultrastructural analysis reveals the prevalence of putative microglial filopodial protrusions, which are targeting excitatory and inhibitory synapses, some of which contain phagocytic inclusions at various distances from their distal extremities to the microglial cell bodies. These observations thus suggest that cell-to-cell contacts mediated by microglial filopodia might be a crucial preliminary step in the elimination of synaptic structures in a neuroinflammatory milieu that occurs in HAND.
authors.affiliation: Axe Neurosciences; Centre de recherche du CHU de Québec; and Department of Molecular Medicine; Université Laval; Québec, QC Canada.
authors.forename: Marie-Ève
authors.initials: MÈ
authors.lastname: Tremblay
authors.affiliation: Center for Neural Development and Disease; University of Rochester; Rochester, NY USA.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Marker
authors.affiliation: Center for Neural Development and Disease; University of Rochester; Rochester, NY USA.
authors.forename: Jenna M
authors.initials: JM
authors.lastname: Puccini
authors.affiliation: Atlanta Department of Veterans Affairs Medical Center; Decatur, GA USA.
authors.forename: E Chris
authors.initials: EC
authors.lastname: Muly
authors.affiliation: Center for Neural Development and Disease; University of Rochester; Rochester, NY USA.
authors.forename: Shao-Ming
authors.initials: SM
authors.lastname: Lu
authors.affiliation: Center for Neural Development and Disease; University of Rochester; Rochester, NY USA.
authors.forename: Harris A
authors.initials: HA
authors.lastname: Gelbard
keywords: Axon terminal; Cerebral cortex; Dendrite; Dendritic spine; Filopodia; Microglia; Mouse; Tat; Ultrastructure