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Astrocytes play a major neuroprotective role, producing high levels of anti\u2010oxidants including metallothionein\u2010I and \u2010II (MT\u2010I\/II). In the present study we characterized the immunoreactive profile of MT\u2010I\/II in the temporal cortex of the Cognitive Function and Ageing Study (CFAS) aging population\u2010representative neuropathology cohort, and examined H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010modulation of <jats:italic>MT<\/jats:italic> transcription by human astrocytes. MT\u2010I\/II is primarily expressed by astrocytes in the aging brain, but is also associated with pyramidal neurons in a small proportion of cases. Astrocyte expression of MT\u2010I\/II does not correlate with Alzheimer\u2010type pathology (A\u03b2 plaques and neurofibrillary tangles) but does relate to astrocyte oxidative DNA damage (<jats:italic>r<\/jats:italic><jats:sub>s<\/jats:sub>\u2009=\u2009.312, <jats:italic>p<\/jats:italic>\u2009=\u2009.006) and the astrocyte response to oxidative DNA damage <jats:italic>in vivo<\/jats:italic> (<jats:italic>r<\/jats:italic><jats:sub>s<\/jats:sub>\u2009=\u2009.238, <jats:italic>p<\/jats:italic>\u2009=\u2009.04), and <jats:italic>MT<\/jats:italic> gene expression is significantly induced in human astrocytes response to oxidative stress <jats:italic>in vitro<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009=\u2009.01). In contrast, neuronal MT\u2010I\/II does not relate to oxidative DNA damage or the neuronal DNA damage response, but is significantly higher in cases with high levels of local tangle pathology (<jats:italic>p<\/jats:italic>\u2009=\u2009.007). As MT\u2010I\/II is neuroprotective against oxidative stress, modulation of MT\u2010I\/II expression is a potential therapeutic target to treat the onset and progression of cognitive impairment.<\/jats:p>","DOI":"10.1002\/glia.23465","type":"journal-article","created":{"date-parts":[[2018,8,11]],"date-time":"2018-08-11T03:50:05Z","timestamp":1533959405000},"page":"2316-2323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Metallothionein\u2010I\/II expression associates with the astrocyte DNA damage response and not Alzheimer\u2010type pathology in the aging brain"],"prefix":"10.1002","volume":"66","author":[{"given":"Rachel","family":"Waller","sequence":"first","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience University of Sheffield  Sheffield United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Murphy","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience University of Sheffield  Sheffield United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire J","family":"Garwood","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience University of Sheffield  Sheffield United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Jennings","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience University of Sheffield  Sheffield United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R","family":"Heath","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience University of Sheffield  Sheffield United 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