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Poster Sessions

Finding a New Treatment for Neuropathic Pain: Targeting the GABA(A) Receptor on Microglia

Brandon Mikulsky

Mentor 1

Alexander Arnold

Location

Union Wisconsin Room

Start Date

27-4-2018 1:00 PM

Description

Glial cells are the most abundant cell type in the central nervous system (CNS), within which they play a variety of physiological roles. One type of glial cell, microglia, have been found to be the primary immune cells within the CNS. Recent studies showed that microglia have a growing role in neurological disorders, such as Multiple Sclerosis, Alzheimer’s disease, and neuropathic pain (NP). Earlier experiments in the Arnold lab demonstrated that imidazobenzodiazepines can reduce lung inflammation in asthma mouse models by selectively targeting the gamma aminobutyric acid type A (GABA_A) receptors expressed on white blood cells, which share a common developmental lineage with microglia. Our collaborators have shown that targeting GABA_A receptors on microglia within the spinal cord using imidazobenzodiazepines can reduce neuropathic pain, however details of this mechanism are unknown. Currently, cell cultures of immortalized human and mouse microglia are being maintained in the Arnold lab to investigate the effects of imidazobenzodiazepines. We present the change of intercellular calcium upon stimulation with ATP and the reduction of nitric oxide (NO) in the presence of selective GABA_AR agonists. These experiments will aid to better understand the anti-inflammatory properties of these compounds and to select potent and safe lead compounds for a more effective NP treatment.

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COinS

Apr 27th, 1:00 PM

Finding a New Treatment for Neuropathic Pain: Targeting the GABA(A) Receptor on Microglia

Union Wisconsin Room

Glial cells are the most abundant cell type in the central nervous system (CNS), within which they play a variety of physiological roles. One type of glial cell, microglia, have been found to be the primary immune cells within the CNS. Recent studies showed that microglia have a growing role in neurological disorders, such as Multiple Sclerosis, Alzheimer’s disease, and neuropathic pain (NP). Earlier experiments in the Arnold lab demonstrated that imidazobenzodiazepines can reduce lung inflammation in asthma mouse models by selectively targeting the gamma aminobutyric acid type A (GABA_A) receptors expressed on white blood cells, which share a common developmental lineage with microglia. Our collaborators have shown that targeting GABA_A receptors on microglia within the spinal cord using imidazobenzodiazepines can reduce neuropathic pain, however details of this mechanism are unknown. Currently, cell cultures of immortalized human and mouse microglia are being maintained in the Arnold lab to investigate the effects of imidazobenzodiazepines. We present the change of intercellular calcium upon stimulation with ATP and the reduction of nitric oxide (NO) in the presence of selective GABA_AR agonists. These experiments will aid to better understand the anti-inflammatory properties of these compounds and to select potent and safe lead compounds for a more effective NP treatment.