Year: 2011
Type: dissertation
Abstract: One aspect of this project set out to examine the effects of methamphetamine (METH) on the accumulation of cellular reactive oxygen species (ROS) and the expression of the mu-opioid receptor (MOR) in a dopaminergic cell line, SH-SY5Y, in order to delineate a possible role for ROS signaling in the coupling of dopaminergic and opioidergic pathways in neuronal cells.Prior evidence indicates neuronal cells treated with METH accumulate dopamine in the synaptic cleft which can lead to increased levels of ROS.Uncovering a role for ROS in increasing MOR expression in response to METH may provide a therapeutic target aimed at reducing the already established phenomenon of METH cross-sensitization to morphine, two drugs with high potential for abuse.A second aspect of this project investigated the mechanism by which lipopolysaccharide (LPS) exposure alters MOR expression in immune and neuronal cells.Previous research notes the exposure to LPS increases the production of ROS in murine macrophages.Also, activation of MOR effects functions associated with the immune response.Therefore, uncovering a role for ROS in increasing MOR expression in immune and neuronal cell types could provide additional insights in how to address problems associated with LPSinduced inflammatory response and the subsequent acceleration of sepsis seen with morphine treatment.The data presented here show that METH's effect on MOR expression is dependent upon sub-lethal levels of intracellular ROS increased by METH treatment, which suggests a possible coupling of METH-and opiate-mediated intracellular signaling.In addition, work from the second portion of this project found that LPS stimulated the intracellular ROS accumulation and MOR expression in macrophage-like TPA-HL-60 cells.Conditioned medium from the LPS-stimulated TPA-HL-60 cells increased MOR expression in SH-SY5Y cells, a neuronal cell model, through actions mediated by TPA-HL-60 secreted TNF-a and GM-CSF.These data indicate that the endotoxin, LPS, modulates MOR expression in nervous and immune cells via ROS signaling, and demonstrates the crosstalk that exists within the neuroimmune axis.
Author: Erik F. Langsdorf
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1607316461