Quantitative Study of the Effect of Progesterone on the Diabetic Sural Nerves in Rats
DOI:
https://doi.org/10.3923/pjn.2017.906.913Keywords:
Diabetes, myelinated nerve fibers, myelin sheath, peripheral nerves, progesteroneAbstract
Objective: The quantitative effects of progesterone injection on the diabetic peripheral nerves with peripheral neuropathy was studied in this experiment. Methodology: Forty two-months-old male albino rats were used in the present study (4 animals as normal control). Diabetes was inducted in 36 animals by a single intravenous injection of freshly prepared streptozotocin (STZ) (65 mg kg–1, Sigma, Milano, Italy) in citrate buffer 0.09 M, pH 4.8 in each animal. The diabetic animals were divided into two groups (18 diabetic control and 18 received 16 times of injection of progesterone). All the specimens were processed for light microscopic study and were photographed at 40X than at 100X. The obtained photographs were studied using the image analyzing system. The myelinated nerve fibers were studied quantitatively (diameters of nerve fibers and axons, surface areas, number and myelin thickness). The obtained values were statistical analyzed using t-test and were compared. Results: There were significant increase in the diameters of nerve fibers and axons, surface areas, number and myelin thickness in the myelinated diabetic nerves treated with progesterone than that of the diabetic control. The diabetic nerves showed significant decrease in the above parameters compared to the normal control. Conclusion: Progesterone injection has neuroprotective properties and can ameliorate the structural changes in the diabetic nerves.
References
Sugimoto, K., Y. Murakawa and A.A.F. Sima, 2000. Diabetic neuropathy-a continuing enigma. Diabetes/Metab. Res. Rev., 16: 408-433.
Tesfaye, S., A.J.M. Boulton, P.J. Dyck, R. Freeman and M. Horowitz et al., 2010. Diabetic neuropathies: Update on definitions, diagnostic criteria, estimation of severity and treatments. Diabetes Care, 33: 2285-2293.
Vinik, A.I., T.S. Park, K.B. Stansberry and G.L. Pittenger, 2000. Diabetic neuropathies. Diabetology, 43: 957-973.
Eckersley, L., 2002. Role of the Schwann cell in diabetic neuropathy. Int. Rev. Neurobiol., 50: 293-321.
Greene, D.A., S. Lattimer-Greene and A.A. Sima, 1989. Pathogenesis of diabetic neuropathy: Role of altered phosphoinositide metabolism. Crit. Rev. Neurobiol., 5: 143-219.
Ji, Z.H., Z.J. Liu, Z.T. Liu, W. Zhao and B.A. Williams et al., 2017. Diphenyleneiodonium mitigates bupivacaine-induced sciatic nerve damage in a diabetic neuropathy rat model by attenuating oxidative stress. Anesth. Analgesia, 125: 653-661.
Bianchi, R., B. Buyukakilli, M. Brines, C. Savino and G. Cavaletti et al., 2004. Erythropoietin both protects from and reverses experimental diabetic neuropathy. Proc. Natl. Acad. Sci. USA., 101: 823-828.
Lauria, G., M. Morbin, R. Lombardi, M. Borgna, G. Mazzoleni, A. Sghirlanzoni and D. Pareyson, 2003. Axonal swellings predict the degeneration of epidermal nerve fibers in painful neuropathies. Neurology, 61: 631-636.
Lauria, G., R. Lombardi, M. Borgna, P. Penza and R. Bianchi et al., 2005. Intraepidermal nerve fiber density in rat foot pad: Neuropathologic-neurophysiologic correlation. J. Peripheral Nervous Syst., 10: 202-208.
Underwood, R.A., N.S. Gibran, L.A. Muffley, M.L. Usui and J.E. Olerud, 2001. Color subtractive-computer-assisted image analysis for quantification of cutaneous nerves in a diabetic mouse model. J. Histochem. Cytochem., 49: 1285-1291.
Luo, Z.J., R.H.M. King, J. Lewin and P.K. Thomas, 2002. Effects of nonenzymatic glycosylation of extracellular matrix components on cell survival and sensory neurite extension in cell culture. J. Neurol., 249: 424-431.
Conti, G., E. Scarpini, P. Baron, S. Livraghi and M. Tiriticco et al., 2002. Macrophage infiltration and death in the nerve during the early phases of experimental diabetic neuropathy: A process concomitant with endoneurial induction of IL-1β and p75NTR. J. Neurol. Sci., 195: 35-40.
Hu, G., F. Zhai, F. Mo, L. He, W. Shen and H. Wang, 2017. Effectiveness and feasibility of nailfold microcirculation test to screen for diabetic peripheral neuropathy. Diabetes Res. Clin. Pract., 131: 42-48.
Li, Y.B., Q. Wu, J. Liu, Y.Z. Fan, K.F. Yu and Y. Cai, 2017. miR-199a-3p is involved in the pathogenesis and progression of diabetic neuropathy through downregulation of SerpinE2. Mol. Med. Rep., 16: 2417-2424.
Hoffman, E.M., N.P. Staff, J.M. Robb, J.L.S. Sauver, P.J. Dyck and C.J. Klein, 2015. Impairments and comorbidities of polyneuropathy revealed by population-based analyses. Neurology, 84: 1644-1651.
Rolim, L.C., E.M.K. da Silva, J.R. de Sa and S.A. Dib, 2017. A systematic review of treatment of painful diabetic neuropathy by pain phenotype versus treatment based on medical comorbidities. Front. Neurol., Vol. 8.
Tesfaye, S., N. Chaturvedi, S.E.M. Eaton, J.D. Ward and C. Manes et al., 2005. Vascular risk factors and diabetic neuropathy. N. Engl. J. Med., 352: 341-350.
Melcangi, R.C., V. Magnaghi, M. Galbiati, B. Ghelarducci, L. Sebastiani and L. Martini, 2000. The action of steroid hormones on peripheral myelin proteins: A possible new tool for the rebuilding of myelin? J. Neurocytol., 29: 327-339.
Melcangi, R.C., V. Magnaghi, M. Galbiati and L. Martini, 2001. Formation and effects of neuroactive steroids in the central and peripheral nervous system. Int. Rev. Neurobiol., 46: 145-176.
Melcangi, R.C., E. Leonelli, V. Magnaghi, G. Gherardi, L. Nobbio and A. Schenone, 2003. Mifepristone (RU 38486) influences expression of glycoprotein Po and morphological parameters at the level of rat sciatic nerve: In vivo observations. Exp. Neurol., 184: 930-938.
Azcoitia, I., E. Leonelli, V. Magnaghi, S. Veiga, L.M. Garcia-Segura and R.C. Melcangi, 2003. Progesterone and its derivatives dihydroprogesterone and tetrahydroprogesterone reduce myelin fiber morphological abnormalities and myelin fiber loss in the sciatic nerve of aged rats. Neurobiol. Aging, 24: 853-860.
Sereda, M.W., G.M. Zu Horste, U. Suter, N. Uzma and K.A. Nave, 2003. Therapeutic administration of progesterone antagonist in a model of Charcot-Marie-Tooth disease (CMT-1A). Nat. Med., 9: 1533-1537.
Leonelli, E., J.G. Yague, M. Ballabio, I. Azcoitia and V. Magnaghi et al., 2005. Ro5-4864, a synthetic ligand of peripheral benzodiazepine receptor, reduces aging-associated myelin degeneration in the sciatic nerve of male rats. Mech. Ageing Dev., 126: 1159-1163.
El-Etr, M., M. Rame, C. Boucher, A. Ghoumari and N. Kumar et al., 2015. Progesterone and nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex. Glia, 63: 104-117.
Melcangi, R.C., V. Magnaghi, I. Cavarretta, L. Martini and F. Piva, 1998. Age-induced decrease of glycoprotein Po and myelin basic protein gene expression in the rat sciatic nerve. Repair by steroid derivatives. Neuroscience, 85: 569-578.
Fowler, M.J., 2008. Microvascular and macrovascular complications of diabetes. Clin. Diabetes, 26: 77-82.
Boulton, A.J.M., F.A. Gries and J.A. Jervell, 1998. Guidelines for the diagnosis and outpatient management of diabetic peripheral neuropathy. Diabetic Med., 15: 508-514.
Said, G., 2007. Diabetic neuropathy: A review. Nat. Clin. Pract. Neurol., 3: 331-340.
Greene, D.A., A.A. Sima, M.J. Stevens, E.L. Feldman and S.A. Lattimer, 1992. Complications: Neuropathy, pathogenetic considerations. Diabetes Care, 15: 1902-1925.
Sato, A., Y. Sato and H. Suzuki, 1985. Aging effects on conduction velocities of myelinated and unmyelinated fibers of peripheral nerves. Neurosci. Lett., 53: 15-20.
Felitsyn, N., P.W. Stacpoole and L. Notterpek, 2007. Dichloroacetate causes reversible demyelination in vitro: Potential mechanism for its neuropathic effect. J. Neurochem., 100: 429-436.
Lee, H.K., Y.K. Shin, J. Jung, S.Y. Seo, S.Y. Baek and H.T. Park, 2009. Proteasome inhibition suppresses Schwann cell dedifferentiation in vitro and in vivo. Glia, 57: 1825-1834.
Kennedy, J.M. and D.W. Zochodne, 2002. Influence of experimental diabetes on the microcirculation of injured peripheral nerve: Functional and morphological aspects. Diabetes, 51: 2233-2240.
Veiga, S., E. Leonelli, M. Beelke, L.M. Garcia-Segura and R.C. Melcangi, 2006. Neuroactive steroids prevent peripheral myelin alterations induced by diabetes. Neurosci. Lett., 402: 150-153.
Leonelli, E., R. Bianchi, G. Cavaletti, D. Caruso and D. Crippa et al., 2007. Progesterone and its derivatives are neuroprotective agents in experimental diabetic neuropathy: A multimodal analysis. Neuroscience, 144: 1293-1304.
Sameni, H.R., M. Panahi, A. Sarkaki, G.H. Saki and M. Makvandi, 2008. The neuroprotective effects of progesterone on experimental diabetic neuropathy in rats. Pak. J. Biol. Sci., 11: 1994-2000.
Schumacher, M., R. Guennoun, D.G. Stein and A.F. De Nicola, 2007. Progesterone: Therapeutic opportunities for neuroprotection and myelin repair. Pharmacol. Therapeut., 116: 77-106.
Melcangi, R.C., I. Azcoitia, M. Ballabio, I. Cavarretta and L.C. Gonzalez et al., 2003. Neuroactive steroids influence peripheral myelination: A promising opportunity for preventing or treating age-dependent dysfunctions of peripheral nerves. Progr. Neurobiol., 71: 57-66.
Chavez-Delgado, M.E., U. Gomez-Pinedo, A. Feria-Velasco, M. Huerta-Viera and S.C. Castaneda et al., 2005. Ultrastructural analysis of guided nerve regeneration using progesterone- and pregnenolone-loaded chitosan prostheses. J. Biomed. Mater. Res. Part B: Applied Biomater., 74: 589-600.
Benito, C., C.M. Davis, J.A. Gomez-Sanchez, M. Turmaine and D. Meijer et al., 2017. STAT3 controls the long-term survival and phenotype of repair Schwann cells during nerve regeneration. J. Neurosci., 37: 4255-4269.
Jessen, K.R., R. Mirsky and A.C. Lloyd, 2015. Schwann cells: Development and role in nerve repair. Cold Spring Harbor Perspect. Biol., Vol. 7.
Brinton, R.D., R.F. Thompson, M.R. Foy, M. Baudry and J. Wang et al., 2008. Progesterone receptors: Form and function in brain. Front. Neuroendocrinol., 29: 313-339.
Stein, D.G., 2008. Progesterone exerts neuroprotective effects after brain injury. Brain Res. Rev., 57: 386-397.
Conneely, O.M., J. Mulac-Jericevic, F. DeMayo, J.P. Lydon and B.W. O'Malley, 2002. Reproductive functions of progesterone receptors. Recent Progr. Hormone Res., 57: 339-355.
Boonyaratanakornkit, V., E. McGowan, L. Sherman, M.A. Mancini, B.J. Cheskis and D.P. Edwards, 2007. The role of extranuclear signaling actions of progesterone receptor in mediating progesterone regulation of gene expression and the cell cycle. Mol. Endocrinol., 21: 359-375.
Vicent, G.P., C. Ballare, A.S. Nacht, J. Clausell and A. Subtil-Rodriguez et al., 2008. Convergence on chromatin of non-genomic and genomic pathways of hormone signaling. J. Steroid Biochem. Mol. Biol., 109: 344-349.
Thomas, P., 2008. Characteristics of Membrane Progestin Receptor Alpha (mPRα) and Progesterone Membrane Receptor Component 1 (PGMRC1) and their roles in mediating rapid progestin actions. Front. Neuroendocrinol., 29: 292-312.
Losel, R.M., D. Besong, J.J. Peluso and M. Wehling, 2008. Progesterone receptor membrane component 1-many tasks for a versatile protein. Steroids, 73: 929-934.
Hosie, A.M., M.E. Wilkins, H.M.A. da Silva and T.G. Smart, 2006. Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites. Nature, 444: 486-489.
Cai, W., Y. Zhu, K. Furuya, Z. Li, M. Sokabe and L. Chen, 2008. Two different molecular mechanisms underlying progesterone neuroprotection against ischemic brain damage. Neuropharmacology, 55: 127-138.
Downloads
Published
Issue
Section
License
Copyright (c) 2017 The Author(s)
This work is licensed under a Creative Commons Attribution 4.0 International License.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
