Article

Activation of the intrinsic cell death pathway, increased apoptosis and modulation of astrocytes in the cerebellum of diabetic rats.

Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Neurobiology of Disease (impact factor: 5.4). 09/2006; 23(2):290-9. DOI:10.1016/j.nbd.2006.03.001 pp.290-9
Source: PubMed

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.

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Keywords

1 week
 
brain area
 
caspases 3
 
caspases 7
 
cell death
 
cell loss
 
cleaved caspase 3
 
Colocalization
 
diabetes
 
diabetes mellitus results
 
diabetic rats
 
functional changes
 
GFAP
 
GFAP levels paralleled modifications
 
glial fibrillary acidic protein
 
Poorly
 
proliferating cell nuclear antigen
 
proliferating GFAP-positive cells
 
streptozotocin-induced diabetic rats cell death
 
TUNEL-positive cells