title: Increased astrocyte reactivity in the hippocampus of murine models of type 1 diabetes: the nonobese diabetic (NOD) and streptozotocin-treated mice.
abstract: Diabetes can be associated with cerebral dysfunction in humans and animal models of the disease. Moreover, brain anomalies and alterations of the neuroendocrine system are present in type 1 diabetes (T1D) animals, such as the spontaneous nonobese diabetic (NOD) mouse model and/or the pharmacological streptozotocin (STZ)-induced model. Because of the prevalent role of astrocytes in cerebral glucose metabolism and their intimate connection with neurones, we investigated hippocampal astrocyte alterations in prediabetic and diabetic NOD mice and STZ-treated diabetic mice. The number and cell area related to the glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes were quantified in the stratum radiatum region of the hippocampus by computerized image analysis in prediabetic (2, 4 and 8 weeks of age) and diabetic (16-week-old) NOD female mice, age and sex-matched lymphocyte-deficient NODscid and C57BL/6 control mice and, finally, STZ-induced diabetic and vehicle-treated nondiabetic 16-week-old C57BL/6 female mice. Astrocyte number was higher early in life in prediabetic NOD and NODscid mice than in controls, when transient hyperinsulinemia and low glycemia were found in these strains. The number and cell area of GFAP(+) cells further increased after the onset of diabetes in NOD mice. Similarly, in STZ-treated diabetic mice, the number of GFAP(+) cells and cell area were higher than in vehicle-treated mice. In conclusion, astrocyte changes present in genetic and pharmacological models of T1D appear to reflect an adaptive process to alterations of glucose homeostasis.
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biologa y Medicina Experimental, Buenos Aires, Argentina.
authors.forename: Flavia E
authors.initials: FE
authors.lastname: Saravia
authors.forename: Yanina
authors.initials: Y
authors.lastname: Revsin
authors.forename: Maria Claudia
authors.initials: MC
authors.lastname: Gonzalez Deniselle
authors.forename: Susana L
authors.initials: SL
authors.lastname: Gonzalez
authors.forename: Paulina
authors.initials: P
authors.lastname: Roig
authors.forename: Analia
authors.initials: A
authors.lastname: Lima
authors.forename: Françoise
authors.initials: F
authors.lastname: Homo-Delarche
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: De Nicola
mesh_terms: D000367:Age Factors; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001786:Blood Glucose / Q000187:drug effects / Q000235:genetics; D048429:Cell Size / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology / Q000503:physiopathology*; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D006706:Homeostasis / Q000502:physiology; D006946:Hyperinsulinism / Q000235:genetics; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D005904:Glial Fibrillary Acidic Protein; D007328:Insulin; D005947:Glucose