title: Activation of microglia and induction of pro-inflammatory cytokines in the hippocampus of type 2 diabetic rats.
abstract: OBJECTIVE
  The majority of immune cells in the brain are comprised of microglia, which undergo morphological changes when activated to remove damaged neurons and infectious agents from the brain tissue. In this study, we investigated the effects of type 2 diabetes on microglial activation and the subsequent secretion of pro-inflammatory cytokines, such as interferon-gamma (IFN-gamma) and interleukin-1beta (IL-1beta), in the hippocampus using Zucker diabetic fatty (ZDF) rats and Zucker lean control (ZLC) rats at various diabetic stages.
  
  
  METHODS
  Zucker lean control and Zucker diabetic fatty rats were sacrificed at 12 (early diabetic stage), 20, or 30 weeks of age (chronic diabetic stage), and the hippocampus was obtained via transcardiac perfusion or dissection for immunohistochemistry and western blot analysis, respectively.
  
  
  RESULTS
  Zucker diabetic fatty rats demonstrated significantly higher glucose levels at 12 and 30 weeks of age compared to ZLC rats. Microglia immunoreactive to ionized calcium-binding adapter molecule 1 (Iba-1) had hypertrophied cytoplasm with retracted processes at 30 weeks of age. In contrast, Iba-1-immunoreactive microglia displayed similar morphology in ZDF and ZLC rats at 12 and 20 weeks of age. Similarly, IFN-gamma and IL-1beta protein levels were significantly increased in ZDF rats compared to ZLC rats at 30 weeks of age, but not at 12 and 20 weeks of age. Interleukin-1beta immunoreactivity in the ZDF rats predominantly increased in the dentate gyrus and CA1 region of the hippocampus compared to that of ZLC rats at 30 weeks of age. In addition, IL-1beta immunoreactive structures in ZDF rats at 30 weeks of age were detected near the astrocytes and microglia.
  
  
  CONCLUSIONS
  These results suggest that chronic diabetes activates microglia and significantly increases pro-inflammatory cytokine levels in the hippocampus.
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Nam
authors.forename: Ok Kyu
authors.initials: OK
authors.lastname: Park
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Yoo
authors.forename: Woosuk
authors.initials: W
authors.lastname: Kim
authors.forename: Sun Shin
authors.initials: SS
authors.lastname: Yi
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.forename: Je Kyung
authors.initials: JK
authors.lastname: Seong
authors.forename: Yeo Sung
authors.initials: YS
authors.lastname: Yoon
mesh_terms: D000208:Acute Disease; D000375:Aging / Q000276:immunology / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D001786:Blood Glucose / Q000502:physiology; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D017628:Microglia / Q000473:pathology / Q000502:physiology*; D011924:Rats, Zucker
chemical_list: C100745:Aif1 protein, rat; D001786:Blood Glucose; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D008840:Microfilament Proteins; D007371:Interferon-gamma
keywords: Diabetes,; Hippocampus,; Interferon-gamma,; Interleukin-1beta; Ionized calcium-binding adapter molecule,; Microglia,