Vulnerability for apoptosis in the hippocampal dentate gyrus of STZ-induced diabetic rats with cognitive impairment.
BACKGROUND
Hyperglycemia impaired hippocampal network via triggering suicide program of immanent neurons, this is regarded as an etiological factor for diabetic cognition deficits.


OBJECTIVE
To investigate the occurrence of apoptosis in the hippocampal dentate gyrus of streptozotocin (STZ)-induced diabetic rats with cognitive impairment and assess the gene and protein expression of the apoptotic proteins bax, bcl-2, and caspase-3.


METHODS
Four weeks after the verification of STZ-induced diabetes, diabetic rats with and without cognitive decline subgroups were subsequently assigned according to Morris water maze test. The expression levels of apoptotic proteins were measured using real-time RT-PCR and western blotting, respectively. Neuronal apoptosis was detected by TUNEL staining and electron microscopy.


RESULTS
In the dentate gyrus of the rats with cognitive decline, Bcl-2 exhibited lower gene and protein levels, whereas a higher expression of bax was detected contributing to a significant increase in their mean bax/bcl-2 ratio. However, caspase-3 was not activated. Statistically different numbers of TUNEL-staining cells and features of apoptosis were no found.


CONCLUSIONS
The higher bax/bcl ratio probably represents neurons of dentate gyrus vulnerable to apoptosis in the diabetes with cognitive decline. However, the normal caspase-3 level suggests that apoptosis is not active in this illness phase.
Department of Neurology, The Affiliated ZhongDa Hospital of Southeast University, No.87 DingJiaQiao Road, Nanjing, 210009, People's Republic of China.
Yi-jing
YJ
Guo
Shao-hua
SH
Wang
Yang
Y
Yuan
Feng-fei
FF
Li
Kuan-ping
KP
Ye
Yan
Y
Huang
Wen-qing
WQ
Xia
Yi
Y
Zhou
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000096:biosynthesis; D003072:Cognition Disorders / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018782:Maze Learning; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3