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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Indomethacin reverses decreased hippocampal cell proliferation in streptozotocin-induced diabetic mice
Metabolic brain disease, v 30(2), pp 555-562
01 Apr 2015
PMID: 25160865
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Diabetes in humans and animals is accompanied by chronic low-grade inflammation, which could be a possible mediator of developing neuropathology and neurobehavioral deficits. The objective of the present study determined if decreasing inflammation could reverse diabetes-induced decreases in hippocampal cell proliferation, one aspect of hippocampal neurogenesis. C57BL/6J mice were made diabetic by administering streptozotocin (STZ; 195 mg/kg). STZ mice or vehicle controls received chronic treatment with the non-steroidal anti-inflammatory drug indomethacin (2 mg/kg for 14 days). Levels of glucose, corticosterone and cytokines were measured from plasma, cell proliferation was measured using BrdU incorporation in the hippocampus and TNF-alpha R1 and TNF-alpha R2 mRNA was measured using real-time PCR. STZ-induced diabetes increased plasma levels of glucose and corticosterone and decreased body weight. Cell proliferation in the hippocampus was reduced in diabetic mice by 50 %. The decreased level of cell proliferation was reversed by chronic treatment with indomethacin without changes to corticosterone and glucose levels. Plasma TNF-alpha levels increased in diabetic mice and were normalized by indomethacin treatment whereas IL-1 and IL-6 levels were unchanged by diabetes or indomethacin. In contrast, plasma levels of the cytokines IL-10 and IFN-gamma decreased in diabetic mice and were not affected by indomethacin treatment. STZ-induced diabetes decreased hippocampal expression of TNF-alpha R2 but not TNF-alpha R1 mRNA. Indomethacin ameliorated the effects of STZ on hippocampal neurogenesis independent of corticosterone and glycemic control, possibly by mediating the proinflammatory cytokine TNF-alpha. Inflammation is a potential novel pharmacological target for alleviating neurobehavioral complications arising from diabetes.
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Details
- Title
- Indomethacin reverses decreased hippocampal cell proliferation in streptozotocin-induced diabetic mice
- Creators
- Nancy Ho - University of PennsylvaniaBethany R. Brookshire - University of PennsylvaniaJanet E. Clark - Drexel UniversityIrwin Lucki - University of Pennsylvania
- Publication Details
- Metabolic brain disease, v 30(2), pp 555-562
- Publisher
- Springer Nature
- Number of pages
- 8
- Grant note
- Eastern Nursing Research Society R01-MH86599; F31-NR010853; T32-MH14654 / USPHS; United States Department of Health & Human Services; United States Public Health Service 2009-033 / American Nurses Foundation Small Grants Program T32MH014654 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) F31NR010853 / NATIONAL INSTITUTE OF NURSING RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Nursing Research (NINR)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000350894800023
- Scopus ID
- 2-s2.0-84924150591
- Other Identifier
- 991019168123904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Endocrinology & Metabolism
- Neurosciences