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

被引:15
作者
Hammond, Jennetta W. [1 ]
Qiu, Wen Q. [1 ]
Marker, Daniel F. [1 ]
Chamberlain, Jeffrey M. [1 ]
Greaves-Tunnell, Will [1 ]
Bellizzi, Matthew J. [1 ]
Lu, Shao-Ming [1 ]
Gelbard, Harris A. [1 ]
机构
[1] Univ Rochester, Med Ctr, Ctr Neurotherapeut Discovery, Rochester, NY 14642 USA
关键词
C1q; complement; HIV; synapse; Tat; NEURONAL INJURY; PROTEIN; VIRUS; ACTIVATION; MICROGLIA; CNS; NEUROTOXICITY; CELLS; EXPRESSION; CLEARANCE;
D O I
10.1002/glia.23511
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:2563 / 2574
页数:12
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