Astroglia up-regulate transcription and secretion of 'readthrough' acetylcholinesterase following oxidative stress

Novel and diverse functions of glial cells are currently the focus of much attention [A. Volterra and J. Meldolesi (2005) Nature Rev. 6, 626-640]. Here we present evidence that rat astroglia release acetylcholinesterase (AChE) as part of their response to hypoxic damage. Exposure of astroglia to tert-butyl hydroperoxide, and hence oxidative stress, subsequently leads to a switching in mRNA from the classical membrane-bound T-AChE to a preferential increase in the splice variant for a soluble form, R-AChE, This change in expression is reflected in increased perinuclear and reduced cytoplasmic AChE staining of the insulted glial cells, with a concomitant and marked increase in extracellular secretion that peaks at 1 h post-treatment. An analogous increase in R-AChE, over a similar time scale, occurs in response to psychological stress [D. Kaufer et al. (1998) Nature 93, 373-377], as well as to head injury and stroke [E. Shohami et al. (1999) J. Neurotrauma 6, 365-76]. The data presented here suggest that glial cells may be key chemical intermediaries in such situations and, perhaps more generally in pathological conditions involving oxidative stress, such as neurodegeneration.