Glial cells surround neurons within the brain and serve many functions. The astrocyte can metabolize neurotransmitters, regulate blood flow, and participate in the formation of new synapses. Microglia are important in the brain’s response to disease. Astrocytes and microglia will respond to the immune attack by synthesizing inducible nitric oxide synthase (iNOS), an enzyme that produces nitric oxide (NO•), a highly reactive molecule.
The project will entail studying the modulation of the synthesis of iNOS in vitro, using cells prepared from 2d rat cerebra. Lipopolysaccharide (LPS) a component of bacterial cell walls will be used to activate the cells to synthesize iNOS. Previously, we have found that the anti-depressant fluoxetine (Prozac), paroxetine (Paxil), and the tri-cyclic anti-depressant nortriptyline will increase the release of NO• and synthesis of iNOS induced by LPS. This effect has been observed in mixed glial cultures, where astrocytes and microglia are together. The next step is to produce purified astrocytes and microglia to determine whether the effect of fluoxetine, paroxetine, or nortriptyline is on the astrocyte, microglia, or both.
In addition, we have obtained a microglial cell line, BV2, which has been used by other laboratories in the study of nitrite release with LPS and fluoxetine. We will be testing these cells in combination with the purified astrocytes as well as we work out the conditions to recombine the microglia.
Minimally students should have completed NEUR 170 and BIO 182. Preference will be given to students who have taken Neurochemistry.