The Effects of Alcohol and Age on Astrocytes In Female Rats Following an Inflammatory Stimulus
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ABSTRACT The Effects of Alcohol, and Age on Astrocytes in Female Rats Following an Inflammatory Stimulus (May 2006) Ashley N. Simpson Department of Biology Texas A&M University Research Advisor: Dr. Farida Sohrabji Department of Neuroscience and Experimental Therapeutics Astrocytes are an important support cell within the central nervous system and are an integral part of the blood brain barrier. They participate in inflammatory processes in the brain and may also be influenced by alcohol and age. Thus, the objective of this research was to determine the relationship between alcohol and age following a lipopolysaccharide-induced (LPS) insult in astrocytes derived from young adult and reproductively senescent female rats. To understand the effects of age on astrocytes, primary cultures were derived from reproductively-competent young adult female rats or reproductively senescent female rats. The reproductive senescent females are physiologically similar to human menopause. Thus, our aging model is based on ovarian, not chronological, age. In this study, LPS increased both nitric oxide production and matrix metalloproteinase 9 (MMP-9) activity in young adult and reproductive senescent-derived astrocytes. Matrix metalloproteinases are enzymes that degrade extracellular matrix (ECM) molecules in which cells adhere within the brain. Degradation of the ECM allows for cell migration, but prolonged activation can potentially lead to blood brain barrier degradation. In young adult-derived astrocytes, LPS increased MMP-9 and this was not affected by ethanol. However, in reproductive senescent female-derived astrocytes, the LPS induced increase in MMP-9 was exacerbated in the presence of ethanol. Interestingly, in astrocytes derived from young adults and reproductive senescent females ethanol had no effect on the LPS-induced increase in nitric oxide (NO). Inflammation is a necessary process for the brain to fight infection or viruses and to remove cellular debris following injury. Prolonged inflammation, however, can lead to neurodegeneration. This data suggests that, in female adult rat astrocytes, LPS is able to stimulate NO in the presence or absence of ethanol. However, matrix metalloproteinase activity may be differentially regulated in these two physiologically distinct female populations. Thus ethanol may potentially have a more detrimental impact on the mobility of astrocytes and on the blood brain barrier in the aging brain.
Simpson, Ashley (2009). The Effects of Alcohol and Age on Astrocytes In Female Rats Following an Inflammatory Stimulus. Available electronically from