Y-Aminobutyric acid inhibits synergistic interleukin-6 release and increases intracellular cytokine content in C6 astrocytoma cells in vitro

Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by memory loss and is the most common cause of dementia. It is has been hypothesized that pro-inflammatory cytokines induce the inflammation that is believed to be the cause of the neuronal death that is associated with AD. γ-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the Central Nervous System possessing membrane hyperpolarization or depolarization activities. A decline in GABA may enhance cytokine release in Alzheimer’s disease resulting in neuroinflammation. Therefore, we investigated the GABA-mediated suppression of the synergistic release of interleukin-6 (IL-6) induced by interleukin 1- (IL-1) and tumor necrosis factor (TNF-). In this study our aim was to determine the sub-cellular location of the accumulated IL-6 within Rat C6 astrocytoma cells and to determine the receptor through which GABA is acting to cause the intracellular accumulation of IL-6. We hypothesize that the accumulation occurs within the Golgi apparatus and that the GABAB receptor is acted upon to inhibit the release of IL-6