Hyperglycemia induces the variations of 11β-hydroxysteroid dehydrogenase type 1 and peroxisome proliferator-activated receptor-γ expression in hippocampus and hypothalamus of diabetic rats.
In this paper, we first observed that there were differences in expressions of 11β-HSD1 and PPAR-γ, in hippocampi and hypothalami, among constant hyperglycemia group, control group and the fluctuant glycemia group, using Immunohistochemical analysis. However, whether in expression o f 11β-HSD1 or PPAR-γ, there were no statistic differences between the control group or the fluctuant glycemia group. So, we removed the fluctuant glycemia group, retaining only constant hyperglycemia group and control group, being fed for 8 weeks. After 8 weeks of induction, 11β-HSD1 expression increased and PPAR-γ expression decreased in the constant hyperglycemia group compared with control group, both in hippocampi and hypothalami, by Western Blot. The constant hyperglycemia group also showed impaired cognition in MORRIS watermaze, lower serum corticosterone level, and higher Serum ACTH concentration after 8 weeks. We inferred that the cognition impairment may be related to the abnormal expression of 11β-HSD1 and PPAR-γ in central nerves system. As for 11β-HSD1 is a regulating enzyme, converting the inactive 11-dehydrocorticosterone into the active glucocorticoid corticosterone, thus amplifying GC action in local tissues. It is also well known that high local GC levels can affect the cognitive function. In addition, PPAR-a protective receptor, which is related to cognition.
Department of Endocrinology, Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantan Xili Road, Dongcheng District, Beijing 100050, China.
Wen-wen
WW
Qi
Li-yong
LY
Zhong
Xiao-rong
XR
Li
Guang
G
Li
Zhao-xia
ZX
Liu
Jin-feng
JF
Hu
Nai-hong
NH
Chen
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000096:biosynthesis*; D000305:Adrenal Cortex Hormones / Q000097:blood; D000818:Animals; D003072:Cognition Disorders / Q000209:etiology; D048909:Diabetes Complications / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006624:Hippocampus / Q000201:enzymology*; D006943:Hyperglycemia / Q000097:blood*; D007031:Hypothalamus / Q000201:enzymology*; D008297:Male; D047495:PPAR gamma / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000305:Adrenal Cortex Hormones; D047495:PPAR gamma; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1