Progesterone Treatment on Prefrotal Cortical Demyelination in Experimental Diabetes Induced Brain Injury

  • Adetunji Opeyemi Adebola Department of Anatomy, College of Health and Medical Sciences, Benjamin Carson (SNR) School of Medicine, Babcock University, Ilisan-Remo, Ogun State, Nigeria & Department of Anatomy, College of Health Sciences, University of Ilorin, Kwara State, Nigeria.
Keywords: Myelination, Progesterone, Prefrontal cortex, Streptozotocin


Clinical studies have been looking for an easy way to solve neurodegenerative diseases and in this study, testing of whether effect of progesterone can ameliorate the neurodegenerative effect caused by an induce streptozotocin. Animals were randomly grouped into six (6) groups of eight (8) adult wistar rats each: Group CTR, Group LDP, Group HDP, Group STZ, Group STZ+LDP, and Group STZ+HDP, progesterone was administered daily for seven days after hyperglycemia is confirmed in groups (STZ+LDP and STZ+HDP), likewise administration of Progesterone only is for seven (7) days in groups (LDP and HDP), and the dosesof Progesterone administration varies, low doses of 4 mg/kg/b.w/day to groups (LDP andSTZ+LDP) and high doses of 8 mg/kg/b.w/day to groups (HDP andSTZ+HDP), while groups (CTR andSTZ)received none. Consumption of water and food in each group show an effect on the serum glucose, via an increases in body weight of diabetic animals in comparison with control rat’s body weight which decreases. At the end of the experiment (18wks) the rats are sacrifice and microscopic study of neurotrophic and neuroprotective of rats, prefrontal cortex tissue sampling shows that cells  in the molecular layer of the  induce-hyperglycemia groups rats (STZ, STZ+LDP&STZ+HDP) are reduced and the cortical layer are wider and contain fewer cells compared to the non-induced hyperglycemia groups rats (CTR, LDP&HDP) that has thiner cortical layers and Loss of myelin sheath in the groups(STZ, LDP, and STZ+LDP), in contrast to groups (CTR and STZ+HDP). Involvement of myelinated axons in the morphologic impairment induced by an untreated hyperglycaemic state, an evident in the study, therefore doses of progesterone have an effect on the myelination of axon.


1. Akinola OB, Michael G, Abdul-Azeez S et al. Treatment of alloxan-induced diabetic rats with metformin
or glitazones is associated with amelioration of hyperglycaemia and neuroprotection. The Open
Diabetes Journal 2012; 5: 8-12.
2. Amsten AFT, Goldman-Rakic PS. α2-Adrenergic mechanisms in prefrontal cortex associated with cognitive decline in aged nonhuman primates. Science 1985; 230: 1273-6.
3. Andallu B, Varadacharyulu NC. Antioxidant role of mulberry leaves in streptozotocin-diabetic rats. Clin
Chim Acta 2003; 338: 343.
4. Bancroft, Stevens A. Theory and Practice of Histological Techniques. Churchill Livingstone, Edinburgh. 1982.
5. Berman KE, Weinberger KE. The prefrontal cortex in schizophrenia and other neuropsychiatric diseases: In
vivo physiological correlates of cognitive deficits. Prog Brain Res 1990; 85: 521-36.
6. Cargill RS, Geddes DM, Malcom S et al. Progesterone is protective at the cellular level in an in vitro model
of TBI. Journal of Neurotrauma 1999; 16: 983.
7. Carroll JC, Rosario ER, Chang L et al. Progesterone and
estrogen regulate Alzheimer-like neuropathology in
female 3xTg-AD mice. The Journal of Neuroscience
2007; 27(48): 13357-65.
8. Chao TC, Van Alten PJ, Walker RJ. Steroid sex hormones and macrophage function: modulation of reactive
oxygen intermediates and nitrite release. American Journal of Reproductive Immunology 1994; 32: 43-52.
9. Dalley JW, Cardinal RN, Robbins TW. Prefrontal executive and cognitive functions in rodents: neural
and neurochemical substrates. Neurosci Biobehav Rev 2004; 28: 771-84.
10. Davey P, Brown E, Charani E et al. Interventions to improve antibiotic prescribing practices for hospital
inpatients. Cochrane Database Syst Rev 2013; 4: CD003543.pub3.
11. Drevets DC, Videen TO, Presskorn SH et al. A functional anatomical study of unipolar depression. Journal of
Neuroscience 1992; 12: 3628-41.
12. Garg MC, Ojha S, Bansal DD. Antioxidant status ofstreptozotocin diabetic rats. Indian J Exp Biol 1996;
34: 264-71.
13. Goldman-Rakic PS. Circuitry of primate prefrontal cortex and the regulation of behaviour by representational
memory. The Nervous System 1987; 5: 373-417.
14. Grünblatt E, Salkovic-Petrisic M, Osmanovic J et al. Brain insulin system dysfunction in streptozotocin
intracerebroventricularly treated rats generates hyperphosphorylated tau protein. J Neurochem 2007;
101(3): 757-70.
15. Hoyer S. Glucose metabolism and insulin receptor signal transduction in Alzheimer disease. Eur J Pharmacol
2004; 490: 115-25.
16. Hoyer S, Lannert H. Long-term abnormalities in brain glucose/energy metabolism after inhibition of the
neuronal insulin receptor: implication of tau-protein. J Neural Transm Suppl 2007; 72: 195-202.
17. Roriz-Filho JS, Sá-Roriz TM, Rosset I et al. (Pre) diabetes, brain aging, and cognition. Diabetes and the Nervous
System 2009; 1792: 432-43
18. Keller JN, Mattson MP. Roles of lipid peroxidation in modulation of cellular signalling pathways, cell
dysfunction, and death in the nervous system. Review of Neuroscience 1998; 9: 105.
19. Matsuoka A, Kizuka F, Lee L, et al. progesterone Increases Manganese Superoxide Dismutase Expression via a
cAMP-dependent signalling mediated by noncanonical wnt5a pathway in human endometrial stromal cells. J
Clin Endocrinol Metab 2010; 95: 291-9.
20. Mattes JA. The role of frontal lobe dysfunction in childhood hyperkinesis. Comprehensive Psychiatry
1980; 21: 358-69.
21. Mayer G, Nitsch R, Hoyer S. Effects of changes in peripheral and cerebral glucose metabolism on
locomotor activity, learning and memory in adult male rats. Brain Res 1990; 532: 95-100.
22. Michel F, Bonnefont-Rousselot D, Mas E, et al. Biomarkers of lipid peroxidation: analytical aspects.
Annals of Biological and Clinical Science 2008; 66(6): 605-20.
23. Morrissy S, Xu B, Aguilar D, et al. Inhibition of apoptosis by progesterone in cardiomyocytes. Aging Cell 2010;
9: 799-809.
24. National Toxicology Program. Streptozotocin CAS No. 18883-66-4. National Institute of Environmental Health
Sciences. 11th Ed Report on Carcin, 2005.
25. Nguyen H, Syed V. Progesterone inhibits growth and induces apoptosis in cancer cells through modulation
of ROS. Gynecol Endocrinol 2011; 27: 830-6.
26. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal
Biochem 1979; 95(2): 351-8.
27. Pari, Venkateswaran S. Protective role of Phaseolus vulgaris on changes in the fatty acid composition in
experimental diabetes. Journal of Medicinal Food 2004; 7: 204-9.
28. Roof RL, Duvdevani R, Braswell L et al. Progesterone facilitates cognitive recovery and reduces secondary neuronal loss caused by cortical contusion injury in male rats. Experimental Neurology 1994; 129: 64-9.
29. Martínez-Tellez R, Flores G. Alteration in dendritic morphology of cortical neurons in rats with diabetes
mellitus induced by streptozotocin. Brain Research 2005; 1048: 108-15.
30. Salkovic-Petrisic M, Tribl F, Schmidt M et al. Alzheimer like changes in protein kinase B and glycogen synthase
kinase 3 in rat frontal cortex and hippocampus after damage to the insulin signalling pathway. J Neurochem
2006; 96: 1005-15.
31. Shoham S, Bejar C, Kovalev E et al. Ladostigil prevents gliosis, oxidative-nitrative stress and memory deficits
induced by intracerebroventricular injection of streptozotocin in rats. Neuropharmacology 2006; 52:
32. Sinha AK. Colorimetric assay of catalase. Anal Biochem 1972; 47(2): 389-94.
33. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas.
Physiol Res 2001; 50: 336-46.
34. Todd Preuss M. Do rats have prefrontal cortex? the Rose-Woolsey-Akert program reconsidered. Journal
of Cognitive Neuroscience 1995; 7: 1-24.
35. Watanabe M. Reward expectancy in primate prefrontal neurons. Nature 1996; 382: 629-32.
36. Weinberger DR. A connectionist approach to the prefrontal cortex. Journal of Neuropsychiatry and
Clinical Neuroscience 1993; 5: 241-53.
37. Yanxing C, Zhihou L, Zhu T et al. Intracerebroventricular streptozotocin exacerbates Alzheimer-like changes of
3xTg-AD mice. Mol Neurobiol 2014; 49(1): 547-62.