title: Depressed basal hypothalamic neuronal activity in type-1 diabetic mice is correlated with proinflammatory secretion of HMBG1.
abstract: We recently found indicators of hypothalamic inflammation and neurodegeneration linked to the loss of neuroprotective factors including insulin-like growth factor (IGF-1) and IGF binding protein-2 (IGFBP-3) in mice made diabetic using streptozotocin (STZ). In the current work, a genetic model of type-1 diabetes (Ins2(Akita) mouse) was used to evaluate changes in neuronal activity and concomitant changes in the proinflammatory mediator high-mobility group box-1 (HMBG1). We found basal hypothalamic neuronal activity as indicated by manganese-enhanced magnetic resonance imaging (MEMRI) was significantly decreased in 8 months old, but not 2 months old Ins2(Akita) diabetic mice compared to controls. In tissue from the same animals we evaluated the expression of HMBG1 using immunohistochemistry and confocal microscopy. We found decreased HMBG1 nuclear localization in the paraventricular nucleus of the hypothalamus (PVN) in 8 months old, but not 2 months old diabetic animals indicating nuclear release of the protein consistent with an inflammatory state. Adjacent thalamic regions showed little change in HMBG1 nuclear localization and neuronal activity as a result of diabetes. This work extends our previous findings demonstrating changes consistent with hypothalamic neuroinflammation in STZ treated animals, and shows active inflammatory processes are correlated with changes in basal hypothalamic neuronal activity in Ins2(Akita) mice.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Thinschmidt
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL, USA.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Colon-Perez
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, FL, USA.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Febo
authors.affiliation: Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Caballero
authors.affiliation: Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: King
authors.affiliation: Department of Anesthesia, Indiana University School of Medicine, IN, USA.
authors.forename: Fletcher A
authors.initials: FA
authors.lastname: White
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, IN, USA. Electronic address: mabgrant@iupui.edu.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Grant
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D024243:HMGB1 Protein / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism* / Q000503:physiopathology*; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D009474:Neurons / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein
keywords: Akita; Diabetes; HMBG1; MEMRI; Neuroinflammation