Quetiapine Attenuates Glial Activation and Proinflammatory Cytokines in APP/PS1 Transgenic Mice via Inhibition of Nuclear Factor- B Pathway

Jan 26, 2015The international journal of neuropsychopharmacology

Quetiapine reduces brain support cell activation and inflammation in Alzheimer's model mice by blocking the NF-kappaB pathway

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Abstract

Quetiapine (5mg/kg/d) improves behavioral performance and reduces proinflammatory cytokines in amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic mice after 8 months of treatment.

Quetiapine attenuates glial activation in APP/PS1 mice.
Total levels of Aβ40 and Aβ42 are marginally affected by quetiapine.
Quetiapine suppresses the activation of primary microglia induced by Aβ1-42.
The treatment inhibits the nuclear factor kappa B p65 pathway in both transgenic mice and activated microglia.
Anti-inflammatory effects of quetiapine may be linked to the nuclear factor kappa B pathway.

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BACKGROUND: In Alzheimer's disease, growing evidence has shown that uncontrolled glial activation and neuroinflammation may contribute independently to neurodegeneration. Antiinflammatory strategies might provide benefits for this devastating disease. The aims of the present study are to address the issue of whether glial activation and proinflammatory cytokine increases could be modulated by quetiapine in vivo and in vitro and to explore the underlying mechanism.

METHODS: Four-month-old amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic and nontransgenic mice were treated with quetiapine (5mg/kg/d) in drinking water for 8 months. Animal behaviors, total Aβ levels, and glial activation were evaluated by behavioral tests, enzyme-linked immunosorbent assay, immunohistochemistry, and Western blot accordingly. Inflammatory cytokines and the nuclear factor kappa B pathway were analyzed in vivo and in vitro.

RESULTS: Quetiapine improves behavioral performance, marginally affects total Aβ40 and Aβ42 levels, attenuates glial activation, and reduces proinflammatory cytokines in APP/PS1 mice. Quetiapine suppresses Aβ1-42-induced activation of primary microglia by decresing proinflammatory cytokines. Quetiapine inhibits the activation of nuclear factor kappa B p65 pathway in both transgenic mice and primary microglia stimulated by Aβ1-42.

CONCLUSIONS: The antiinflammatory effects of quetiapine in Alzheimer's disease may be involved in the nuclear factor kappa B pathway. Quetiapine may be an efficacious and promising treatment for Alzheimer's disease targeting on neuroinflammation.

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Quetiapine Attenuates Glial Activation and Proinflammatory Cytokines in APP/PS1 Transgenic Mice via Inhibition of Nuclear Factor- B Pathway

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