Astrocytes function in the brainAstrocytes are the most common cell type in mammalian brain.Glial fibrillary acidic protein (GFAP) and vimentin (Vim) constitute intermediate filaments (known also as nanofilaments) as part of the cytoskeleton in astrocytes.Reactive gliosis is a response of astrocytes to a variety of brain insults that is characterized by hypertrophy of the cell bodies and processes, altered gene expression, increase in the expression of GFAP, Vim and the calcium binding protein S100 (Ridet et al., 1997), and proliferation that may likely occur in some neurodegenerative diseases (Sofroniew, 2009;Sofroniew & Vinters, 2010).In contrast, because reactive astrocytes are ubiquitous in aged central nervous system (CNS) tissue, they are often regarded as uniformly harmful, provoking inflammation, releasing cytotoxins and chemokines that serve no purpose but to inhibit axonal regeneration and increase damage.The wide range of activities that astrocytes can exhibit in vitro contributes to uncertainty over whether these cells exert beneficial or detrimental effects after CNS degeneration.For example, potential protective effects could be provided by glutamate uptake and neurotrophin release, while potential detrimental effects might be caused by the release of inflammatory cytokines and cytotoxic radicals.Little information has been available on the r o l e s p l a y e d b y r e a c t i v e a s t r o c y t e s i n t h e r e s p o n s e t o e x p e r i m e n t a l m o d e l s o f neurodegenerative diseases in vivo.For instance, aged astrocytes exhibit an elevated content of GFAP and of S100 (Barreto et al., 2009;Nichols, 1999).Use of oligonucleotide arrays has yielded the first profile of gene expression from the aging brain of mice and evidence that aging seems to be associated with an inflammatory response and oxidative stress both in neocortex, hippocampus and in cerebellum (Lee et al., 2000;Zeier et al., 2011), with parallels to human neurodegenerative disorders.GFAP is also one of the genes that undergoes a twofold increase in expression.Thus, the GFAP increases of the aged astrocytes may be the result of a response to the inflammatory and oxidative state of the aging brain.Indeed, better comprehension of the features that distinguish a normal, "healthy" old brain from a brain that is at an early stage of a neurodegenerative disease is a key aspect in developing treatments.It is interesting to note that one of the characteristics of astrocytes in the aging brain -the number of astrocytes -is increased by ~20% (Peinado et al., 1998;Pilegaard & Ladefoged, 1996;Rozovsky et al., 1998;Salminen et al., 2011).This response has been compared with reactive gliosis in response to injured or damaged neurons during aging.However, an alternative explanation is that increased number of astrocytes in the aging brain is required to provide the same level of neuroprotection that is present in the brain of a young animal.One hallmark of the cellular response to brain aging, and in neurodegenerative states, is a rapid, dramatic increase in damaging free radicals, including nitric oxide (NO), superoxide, and peroxynitrite (Shibata & Kobayashi, 2008).On the other hand, astrocytes produce the beneficial antioxidants glutathione, superoxide dismutases (SODs 1, 2 and 3), and ascorbate (Figure 1, Anderson & Swanson, 2000;Dringen, 2000;Dringen et al., 2000;Lindenau et al., 2000;Sims et al., 2004).Interestingly, neurons cocultured with astrocyte exhibit higher levels of glutathione compared with neurons cultured alone (Giordano et al., 2009), suggesting that astrocytes provide additional antioxidant defense to neurons (Slemmer et al., 2008).Similarly, astrocytes upregulate HO-1 (heme-oxygenase 1, Figure 2), a 32 kDa stress protein that degrades heme to biliverdin, free iron and carbon monoxide.Although the upregulation of this enzyme has been previously reported to confer neuroprotection following various brain insults (Beschorner et al.,