Progesterone modulates diabetes/hyperglycemia-induced changes in the central nervous system and sciatic nerve.
We investigated the effect of progesterone (P4) treatment on diabetes/hyperglycemia-induced pathological changes in brain, spinal cord and sciatic nerve tissue in male rats. Animals were rendered hyperglycemic by a single dose of streptozotocin (STZ). P4 treatment was started after hyperglycemia was confirmed and body weight and blood glucose levels were monitored once/week for 5weeks. Rats underwent behavioral testing at week 5 and were then euthanized for histology. We assessed the expression of markers of angiogenesis (vascular endothelial growth factor (VEGF)), inflammation (interleukin-6 (IL-6)) and tissue injury (CD11b, NG2, COX2 and matrix metalloproteinase-2 (MMP-2)) in the brain, spinal cord and sciatic nerve. We also examined the regenerative effect of P4 on pathological changes in intra-epidermal nerve fibers (IENF) of the footpads. Diabetes/hyperglycemia led to body weight loss over 5weeks and P4 treatment reduced this loss. At week 5, blood-glucose levels were significantly lower in the P4-treated diabetic group compared to vehicle. Compared to sham or P4-treated groups, the diabetic vehicle group showed hyperactivity on the spontaneous locomotor activity test. Western blot data revealed upregulation of VEGF, IL-6, CD11b, NG2, COX2 and MMP-2 levels in the vehicle group and P4 treatment normalized these expression levels. IENF densities were reduced in the vehicle group and normalized after P4 treatment. We conclude that P4 can reduce some of the chronic pathological responses to STZ-induced diabetes.
Department of Emergency Medicine, Brain Research Laboratory, 1365 Clifton Rd NE, Suite B5100, Emory University School of Medicine, Atlanta, GA 30322, USA.
Fahim
F
Atif
Department of Emergency Medicine, Brain Research Laboratory, 1365 Clifton Rd NE, Suite B5100, Emory University School of Medicine, Atlanta, GA 30322, USA.
Megan C
MC
Prunty
Department of Neurological Surgery, 1365 Clifton Rd NE, Suite B6200, Emory University, Atlanta, Georgia 30322, USA.
Nefize
N
Turan
Department of Emergency Medicine, Brain Research Laboratory, 1365 Clifton Rd NE, Suite B5100, Emory University School of Medicine, Atlanta, GA 30322, USA.
Donald G
DG
Stein
Department of Emergency Medicine, Brain Research Laboratory, 1365 Clifton Rd NE, Suite B5100, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: syousu2@emory.edu.
Seema
S
Yousuf
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D001786:Blood Glucose; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; C577686:interleukin-6, mouse; D011374:Progesterone; D013311:Streptozocin; D020778:Matrix Metalloproteinase 2
hyperglycemia; inflammation; nervous system; progesterone; recovery