Finding a New Treatment in Neuropathic Pain: Targetting the GABA(A) Receptor in Microglia
Mentor 1
Alexander Arnold
Location
Union Wisconsin Room
Start Date
5-4-2019 1:30 PM
End Date
5-4-2019 3:30 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 since 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 (GABAA) receptors expressed on white blood cells, which share a common developmental lineage with microglia. Our collaborators have shown that targeting GABAA 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 GABAAR agonists and measured iNOS expression using rtPCR. 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.
Finding a New Treatment in Neuropathic Pain: Targetting the GABA(A) Receptor in 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 since 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 (GABAA) receptors expressed on white blood cells, which share a common developmental lineage with microglia. Our collaborators have shown that targeting GABAA 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 GABAAR agonists and measured iNOS expression using rtPCR. 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.
