Graduation Year

2010

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Molecular Pharmacology and Physiology

Major Professor

Jun Tan

Co-Major Professor

David Morgan

Committee Member

R. Douglas Shytle

Committee Member

Keith Pennypacker

Committee Member

Craig Doupnik

Keywords

nAChR, α7, cannabinoid, CB2, microglia

Abstract

Neuroinflammation is a major driving force in the progression of neurodegenerative disorders. Nicotinic acetylcholine receptors, as well as cannabinoid CB2 receptors, have been shown to have strong anti-inflammatory properties when activated. These effects are shown, in vivo, to be a result of stimulation of α7 nAChRs and CB2 cannabinoid receptors. Microglia cells, an immune cell in the brain, are shown to express both of these receptor subtypes. The studies detailed herein, investigated the ability of two compounds, nicotine and Δ9-THC, in modulation of inflammatory processes. Stimulation of these receptors on microglia using nicotine and Δ9-THC blocked the activation of these cells, observed through reductions in pro-inflammatory cytokine production. Reductions in inflammation as well as pathology in the PSAPP mouse model of Alzheimer’s Disease were also observed following nicotine and Δ9-THC administration. These data raise the possibility that α7 nAChRs and CB2 cannabinoid receptors may prove to be viable and effective strategy for reducing neuroinflammation observed in neurodegenerative disease.

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