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Progesterone modulates diabetes/hyperglycemia-induced changes in the central nervous system and sciatic nerve
Fahim Atif1, Megan C Prunty1, Nefize Turan2
1Department of Emergency Medicine, Brain Research Laboratory, 1365 Clifton Rd NE, Suite B5100, Emory University School of Medicine, Atlanta, GA 30322, USA.
Abstract:
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.
Insights
Progesterone (P4) treatment mitigated hyperglycemia-induced nerve damage and inflammation in diabetic rats. P4 therapy reduced body weight loss and normalized key pathological markers in the brain, spinal cord, and sciatic nerve.
Area of Science:
- Neuroscience
- Endocrinology
- Diabetology
Background:
- Diabetes/hyperglycemia causes pathological changes in the central and peripheral nervous systems.
- These changes include altered angiogenesis, inflammation, and tissue injury markers.
- The neuroprotective potential of progesterone (P4) in diabetes is not fully understood.
Purpose of the Study:
- To investigate the effect of progesterone (P4) treatment on diabetes/hyperglycemia-induced pathological changes in male rats.
- To assess P4's impact on markers of angiogenesis, inflammation, and tissue injury in neural tissues.
- To examine P4's regenerative effect on intra-epidermal nerve fibers (IENF) in diabetic rats.
Main Methods:
- Male rats were rendered hyperglycemic using streptozotocin (STZ).
- Progesterone (P4) treatment commenced post-hyperglycemia confirmation; body weight and blood glucose monitored weekly for 5 weeks.
- Behavioral testing, Western blot analysis for VEGF, IL-6, CD11b, NG2, COX2, MMP-2, and IENF density assessment were performed.
Main Results:
- P4 treatment reduced hyperglycemia-induced body weight loss and lowered blood glucose levels.
- Diabetic rats exhibited hyperactivity, which was normalized by P4 treatment.
- P4 normalized the upregulation of VEGF, IL-6, CD11b, NG2, COX2, and MMP-2, and restored reduced IENF densities.
Conclusions:
- Progesterone (P4) treatment effectively counteracted several chronic pathological responses to STZ-induced diabetes in rats.
- P4 demonstrated neuroprotective effects by normalizing markers of angiogenesis, inflammation, and tissue injury in neural tissues.
- P4 treatment promoted nerve regeneration, evidenced by the normalization of intra-epidermal nerve fiber densities.
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