University of Nevada, Las Vegas; Center for Academic Enrichment and Outreach
Inflammation within the brain (neuroinflammation) has been associated with a number of neurodegenerative diseases, including Alzheimerʼs disease (AD) (Solito et al., 2012). Within the brain, inflammation is defined broadly as prolonged activation of the brainʼs immune cells, known as glial cells. Excessive activation of glial cells within the brains of AD patients is a hallmark of the disease, however the mechanism by which this contributes to disease pathology is relatively unclear (Jo et al., 2014). Recently, studies have shown that glial cells, known as astrocytes, are able to synthesize and release the inhibitory neurotransmitter GABA (Charles et al., 2003). Further, microglia cells, the primary immunocompetent cells of the brain, have been shown to be GABAceptive cells, which express GABA (B) type receptors (Kuhn et al., 2004). Early characterizations of AD first described alterations in astrocyte location and activation in the disease and interestingly, differences in the total abundance of GABA within the brains of AD patients have recently been reported. Combined, these data provide support for the hypothesis that astrocytes regulate microglia activity through the release of GABA acting at GABA(B) type receptors. The activation of GABA(B) on microglia may serve to reduce the activation status of these microglia, thereby reducing the number of pro-inflammatory cytokines present within the brain (Streit et al., 2002). In the present study, we examined the effects of the GABA(B) agonist baclofen on chronic inflammation in rodents administered lipopolysaccharide (LPS). LPS is a bacterial endotoxin derived from the cell wall of gram-negative bacteria and is capable of mounting an immune response through the activation of toll-like receptor 4 (TLR4). Our data indicate that the administration of baclofen initially attenuated the pyrogenic effects of LPS administration, though this effect was lost after two weeks of injections. The administration of baclofen also rescued deficits in spatial learning and memory seen in animals chronically administered LPS. Furthermore, a significant increase in the total abundance of AB oligomers, believed to play a role in the pathology of AD, was seen in the brains of animals chronically administered LPS. Together, these data provide evidence that the modulation of GABA(B) receptor function altered the immune response evoked by activation of TLR4. These data also provide support for a potential role of GABA(B) in modulating aberrant immune activity seen in AD populations.
Alzheimer's disease; Brain; Brain--Diseases; Encephalitis; GABA; GABA--Receptors; Neuroglia
Biology | Life Sciences | Psychology
Langhardt, M. A.,
Modulatory Effects of GABA(B) Receptor Facilitation in a Model of Chronic Inflammation.
Available at: http://digitalscholarship.unlv.edu/mcnair_posters/49