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We have previously shown that in neonatal rats subjected to hypoxia\u2013ischemia (HI), melatonin administration significantly reduces brain damage. This study assessed whether attenuation of ER stress is involved in the neuroprotective effect of melatonin after neonatal HI. We found that the UPR was strongly activated after HI. Melatonin significantly reduced the neuron splicing of XBP\u20101 mRNA, the increased phosphorylation of eIF2<jats:italic>\u03b1<\/jats:italic>, and elevated expression of chaperone proteins GRP78 and Hsp70 observed after HI in the brain. CHOP, which plays a convergent role in the UPR, was reduced as well. Melatonin also completely prevented the depletion of SIRT\u20101 induced by HI, and this effect was observed in the same neurons that over\u2010express CHOP. These results demonstrate that melatonin reduces ER stress induced by neonatal HI and preserves SIRT\u20101 expression, suggesting that SIRT\u20101, due to its action in the modulation of a wide variety of signaling pathways involved in neuroprotection, may play a key role in the reduction of ER stress and neuroprotection observed after melatonin.<\/jats:p>","DOI":"10.1111\/jpi.12156","type":"journal-article","created":{"date-parts":[[2014,7,2]],"date-time":"2014-07-02T02:31:32Z","timestamp":1404268292000},"page":"192-199","source":"Crossref","is-referenced-by-count":95,"title":["Melatonin reduces endoplasmic reticulum stress and preserves sirtuin 1 expression in neuronal cells of newborn rats after hypoxia\u2013ischemia"],"prefix":"10.1111","volume":"57","author":[{"given":"Silvia","family":"Carloni","sequence":"first","affiliation":[{"name":"Department of Biomolecular Sciences University of Urbino \u2018Carlo Bo\u2019 Urbino 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