Activation of the intrinsic cell death pathway, increased apoptosis and modulation of astrocytes in the cerebellum of diabetic rats.
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.
Lechuga-Sancho
Alfonso M
AM
Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Arroba
Ana I
AI
Frago
Laura M
LM
Pañeda
Covadonga
C
García-Cáceres
Cristina
C
Delgado Rubín de Célix
Arancha
A
Argente
Jesús
J
Chowen
Julie A
JA
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
D005904:Glial Fibrillary Acidic Protein