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Furthermore, levels of matrix metalloproteinase-2 (MMP-2), nucleoside triphosphate diphosphohydrolase-1 (CD39), and ionized calcium-binding adaptor molecule 1 (Iba-1) were utilized to assess inflammatory changes in astrocytes, microglia, and blood vessels. In the diabetic hypothalamus (HYPO), we observed 20% reduction in neuronal soma diameter ( P &lt; 0.05) and reduced neuronal expression of IGFBP-3 (\u221232%, P &lt; 0.05) and IGF-I (\u221215%, P &lt; 0.05) compared with controls at 35 wk. In diabetic HYPO, MMP-2 expression was increased in astrocytes (46%, P &lt; 0.01), and IDO<jats:sup>+<\/jats:sup>cell density rose by (62%, P &lt; 0.05). CD39 expression dropped by 30% ( P &lt; 0.05) in microglia and blood vessels. With 10 wk of systemic treatment using minocycline, an anti-inflammatory agent that crosses the blood-brain barrier, MMP-2, IDO, and CD39 levels normalized ( P &lt; 0.05). Our results suggest that increased IDO and early loss of CD39<jats:sup>+<\/jats:sup>protective cells lead to activation of inflammation in sympathetic centers of the CNS. As a downstream effect, the loss of the neuronal survival factors IGFBP-3 and IGF-I and the neurotoxic products of the kynurenine pathway contribute to the loss of neuronal density observed in the HYPO in T1D.<\/jats:p>","DOI":"10.1152\/ajpendo.00504.2014","type":"journal-article","created":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T09:09:49Z","timestamp":1424941789000},"page":"E688-E698","source":"Crossref","is-referenced-by-count":23,"title":["Loss of survival factors and activation of inflammatory cascades in brain sympathetic centers in type 1 diabetic mice"],"prefix":"10.1152","volume":"308","author":[{"given":"Ping","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Anatomy, School of Medical Sciences, Bosch Institute, The University of Sydney, Camperdown, New South Wales, Australia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey S.","family":"Thinschmidt","sequence":"additional","affiliation":[{"name":"Department of 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