title: Activation of the intrinsic cell death pathway, increased apoptosis and modulation of astrocytes in the cerebellum of diabetic rats.
abstract: Poorly controlled diabetes mellitus results in structural and functional changes in many brain regions. We demonstrate that in streptozotocin-induced diabetic rats cell death is increased and proliferation decreased in the cerebellum, indicating overall cell loss. Levels of both the proform and cleaved forms of caspases 3, 6 and 9 are increased, with no change in caspases 7, 8 or 12. Colocalization of glial fibrillary acidic protein (GFAP) and cleaved caspase 3 and GFAP in TUNEL-positive cells increased in diabetic rats. Changes in GFAP levels paralleled modifications in proliferating cell nuclear antigen (PCNA), increasing at 1 week of diabetes and decreasing thereafter, and proliferating GFAP-positive cells were decreased in the cerebellum of diabetic rats. These results suggest that astrocytes are dramatically affected in the cerebellum, including an increase in cell death and a decrease in proliferation, and this could play a role in the structural and functional changes in this brain area in diabetes.
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
authors.forename: Alfonso M
authors.initials: AM
authors.lastname: Lechuga-Sancho
authors.forename: Ana I
authors.initials: AI
authors.lastname: Arroba
authors.forename: Laura M
authors.initials: LM
authors.lastname: Frago
authors.forename: Covadonga
authors.initials: C
authors.lastname: Pañeda
authors.forename: Cristina
authors.initials: C
authors.lastname: García-Cáceres
authors.forename: Arancha
authors.initials: A
authors.lastname: Delgado Rubín de Célix
authors.forename: Jesús
authors.initials: J
authors.lastname: Argente
authors.forename: Julie A
authors.initials: JA
authors.lastname: Chowen
mesh_terms: D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D002531:Cerebellum / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D020287:In Situ Nick-End Labeling; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
chemical_list: D005904:Glial Fibrillary Acidic Protein