HIV Tat causes synapse loss in a mouse model of HIV-associated neurocognitive disorder that is independent of the classical complement cascade component C1q

Autor: Matthew J. Bellizzi, Shao-Ming Lu, Will Greaves-Tunnell, Wen Q. Qiu, Jeffrey M. Chamberlain, Harris A. Gelbard, Jennetta W. Hammond, Daniel F. Marker
Rok vydání: 2018
Předmět:
0301 basic medicine
Nervous system
Male
HIV Infections
Mice
Transgenic
Nerve Tissue Proteins
Biology
Microgliosis
HIV-associated neurocognitive disorder
Article
Proinflammatory cytokine
Receptors
Interleukin-8A
Synapse
03 medical and health sciences
Cellular and Molecular Neuroscience
Mice
0302 clinical medicine
Bone Marrow
medicine
Animals
Cognitive Dysfunction
Gliosis
Neuroinflammation
Bone Marrow Transplantation
Cerebral Cortex
Complement C1q
Calcium-Binding Proteins
Microfilament Proteins
Complement C3
medicine.disease
Complement system
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Neurology
Gene Expression Regulation
Knockout mouse
Synapses
tat Gene Products
Human Immunodeficiency Virus
Microglia
Neuroscience
030217 neurology & neurosurgery
Zdroj: Glia. 66(12)
ISSN: 1098-1136
Popis: Microglial activation, increased proinflammatory cytokine production, and a reduction in synaptic density are key pathological features associated with HIV-associated neurocognitive disorders (HAND). Even with combination antiretroviral therapy (cART), more than 50% of HIV-positive individuals experience some type of cognitive impairment. Although viral replication is inhibited by cART, HIV proteins such as Tat are still produced within the nervous system that are neurotoxic, involved in synapse elimination, and provoke enduring neuroinflammation. As complement deposition on synapses followed by microglial engulfment has been shown during normal development and disease to be a mechanism for pruning synapses, we have tested whether complement is required for the loss of synapses that occurs after a cortical Tat injection mouse model of HAND. In Tat-injected animals evaluated 7 or 28 days after injection, levels of early complement pathway components, C1q and C3, are significantly elevated and associated with microgliosis and a loss of synapses. However, C1qa knockout mice have the same level of Tat-induced synapse loss as wild-type (WT) mice, showing that the C1q-initiated classical complement cascade is not driving synapse removal during HIV1 Tat-induced neuroinflammation.
Databáze: OpenAIRE
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