Neuroprotective role of 17β estradiol with tachykinin neuropeptide NKB and Aβ (25 - 35) in aging female rat brain

DOI: 10.4236/aar.2013.24019   PDF   HTML   XML   2,885 Downloads   5,251 Views   Citations


The brain experiences structural, molecular and functional alterations during aging. In aging brain tissue, the oxidative stress increases due to decreased activity of antioxidant enzymes and increased oxidative stress leading to neurodegeneration associated with excitotoxicity. In the present study, we observed the effect of tachykinin neuropeptide Neurokinin B (NKB) and amyloid beta fragment Aβ (25 - 35) on the activity of Acetylcholine esterase (AChE) and Lipid peroxidation (LPO) in brains of 17β estradiol (E2) treated aging female rat synaptosomes of different age groups. An in-vitro incubation of E2 treated brain synaptosomes with Aβ (25 - 35) showed toxic effects on all the parameters. The treatment of NKB and combined NKB and Aβ (25 - 35) increased the AChE enzyme activity and decreased the level of LPO in E2 treated aging rats. The treatment of NKB and combined NKB and Aβ (25 - 35) in a concentration dependent manner reversed the effects of aging and Aβ (25 - 35) on AChE and LPO. The present finding suggests that E2 along with NKB reverse aging and Aβ (25 - 35) induced toxicity as well as AChE and LPO levels. The results of the current study showed a possible beneficial role of NKB with E2 inthe age related neurological diseases.

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Jha, R. , Mahdi, A. , Pandey, S. , Baquer, N. and Cowsik, S. (2013) Neuroprotective role of 17β estradiol with tachykinin neuropeptide NKB and Aβ (25 - 35) in aging female rat brain. Advances in Aging Research, 2, 130-136. doi: 10.4236/aar.2013.24019.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Markesbery, W.R. (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radical Biology & Medicine, 23, 134-147.
[2] Jenner, P. (1998) Oxidative mechanisms in nigral cell death in Parkinson’s disease. Movement Disorders, 13, 24-34.
[3] Stocker, R. and Frie, B. (1991) Endogenous antioxidant defense in human blood plasma. In: Sies, H., Ed., Oxidative Stress: Oxidants and Antioxidants, Academic Press, London, 213-243.
[4] Brann, D.W., Krishnan, D., Chandramohan, W., Virendra, B.M. and Mohammad, M.K. (2007) Neurotrophic neuroprotective actions of estrogen: Basic mechanisms and clinical implications. Steroids, 72, 381-405.
[5] Kumar, P., Taha, A., Kale, R.K., Cowsik, S.M. and Baquer, N.Z. (2011) Physiological and biochemical effects of 17β estradiol in aging female rat brain. Experimental Gerontology, 46, 597-605.
[6] Kumar, P., Kale, R.K., McLean, P. and Baquer N.Z. (2011) Protective effects of 17β estradiol on altered age related neuronal parameters in female rat brain. Neuroscience Letters, 502, 56-60.
[7] Meyers, B., Agostino, D.A., Walker, J. and Kritzer, M.F. (2010) Gonadectomy and hormone replacement exert regionand enzyme isoform-specific effects on monoamine oxidase and catechol-o-methyltransferase activity in prefrontal cortex and neostriatum of adult male rats. Neuroscience, 165, 850.
[8] Henderson, V.W. (2010) Action of estrogens in the aging brain: Dementia and cognitive aging. Biochimica et Biophysica Acta, 1800, 1077-1083.
[9] Almeida, T.A., Rojo, J., Nieto, P.M., Pinto, F.M., Hernandez, M., Martin, J.D. and Candenas, M.L. (2004) Tachykinins and tachykinin receptors: Structure and activity relationships. Current Medicinal Chemistry, 11, 20452081.
[10] Patacchini, R., Lecci, A., Holzer, P. and Maggi, C.A. (2004) Newly discovered tachykinins raise new questions about their peripheral roles and the tachykinin nomenclature. Trends in Pharmacological Sciences, 25, 1-3.
[11] Maggi, C.A. and Meli. A. (1988) The sensory-efferent function of capsaicin-sensitive sensory neurons. General Pharmacology, 19, 1-43.
[12] Regoli, D., Boudon, A. and Fauchere, J.L. (1994) Receptors and antagonists for substance P and related peptides. Pharmacological Reviews, 46, 551-599.
[13] Maggi, C.A. (1997) Tachykinins as peripheral modulators of primary afferent nerves and visceral sensitivity. Pharmacological Research, 36, 153-169.
[14] Patak, E.N., Pennefather, J.N. and Story, M.E. (2000) Effects of tachykinins on uterine smooth muscle. Clinical and Experimental Pharmacology and Physiology, 27, 922-927.
[15] Singh, K.P. and Maji, S.K. (2012) Amyloid-like fibril formation by tachykinin neuropeptides and its relevance to amyloid β-protein aggregation and toxicity. Cell Biochemistry and Biophysics, 64, 29-44.
[16] Turska, E., Lachowicz, L. and Wasiak, T. (1985) Effect of analogues of substance P fragments on the MAO activity in rat brain. General Pharmacology, 16, 293-295.
[17] Mantha, A.K., Moorthy, K., Cowsik, S.M. and Baquer, N.Z. (2006) Neuroprotective role of neurokinin B (NKB) on amyloid β (25 35) induced toxicity in aging rat brain synaptosomes: Involvement in oxidative stress and excitotoxicity. Biogerentology, 7, 1-17.
[18] Mantha, A.K., Moorthy, K., Cowsik, S.M. and Baquer, N.Z. (2006) Membrane associated functions of neurokinin B (NKB) on Aβ (25 35) induced toxicity in aging rat brain synaptosomes. Biogerentology, 7, 19-33.
[19] Kowall, N.W., Beal, M.F., Buscigliot, J., Duffyt, L.K. and Yankner, N.W. (1991) An in vivo model for the neurodegenerative effects of β amyloid and protection by substance P. Neurobiology, 88, 7247-7251.
[20] Yankner, B.A., Duffy, L.K. and Kirschner, D.A. (1990) Neurotrophic and neurotoxic effects of amyloid protein: Reversal by tachykinin neuropeptides. Science, 250, 279282.
[21] Pradhan, S.N. (1980) Central neurotransmitters and aging. Life Sciences, 26, 1643-1656.
[22] Tripathy, A. and Srivastava, U.C. (2008) Acetylcholinesterase: A versatile enzyme of nervous system. Annual Review of Neuroscience, 15, 106-111.
[23] Hagihara, M., Nishigaki, I., Maseki, M. and Yagi, K. (1984) Age dependent changes in lipid peroxide levels in the lipoprotein fractions of human serum. The Journals of Gerontology, 39, 269-272.
[24] Kurata, M., Suzuki, M. and Agar, N.S. (1993) Antioxidant systems and erythrocyte life-span in mammals. Comparative Biochemistry and Physiology, 106, 477-487.
[25] Moorthy, K., Yadav, U.C.S., Siddiqui, M.R., Mantha, A.K., Basir, S.F., Sharma, D., Cowsik, S.M. and Baquer, N.Z. (2005) Effect of hormone replacement therapy innormalizing age related neuronal markers in different age groups of naturally menopausal rats. Biogerontology, 6, 345-356.
[26] Moorthy, K., Yadav, U.C.S., Siddiqui, M.R., Basir, S.F., Sharma, D. and Baquer, N.Z. (2004) Effect of estradiol and progesterone treatment on carbohydrate metabolizing enzymes in tissues of aging female rats. Biogerontology, 5, 249-259.
[27] Moorthy, K., Sharma, D., Basir, S.F. and Baquer, N.Z. (2005) Administration of estradiol and progesterone modulate the activities of antioxidant enzyme and aminotransferases in naturally menopausal rats. Experimental Gerontology, 40, 295-302.
[28] Mayanil, C.S., Kazmi, S.M. and Baquer, N.Z. (1982) Na+, K+-ATPase and Mg2+-ATPase activities in different regions of rat brain during alloxan diabetes. Journal of Neurochemistry, 39, 903-908.
[29] Ellman, G.L., Courtney, K.D., Andres Jr., V. and Featherstone, R.M. (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology, 7, 88-95.
[30] Genet, S., Kale, R.K. and Baquer, N.Z. (2002) Alterations in antioxidant enzymes and oxidative damage in experimental diabetic rat tissues: Effect of vanadate and fenugreek (TSP foenum-graecum). Molecular and Cellular Biochemistry, 236, 7-12.
[31] Guzman, R.G., Kendrick, K.M. and Emson, P.C. (1993) Effect of substance P on acetylcholine and dopamine release in the rat striatum: A microdialysis study. Brain Research, 622, 147-154.
[32] Yau, W.M., Mandel, K.G., Dorsett, J.A. and Youther, M.L. (1992) Neurokinin3 receptor regulation of acetylcholine release from myenteric plexus. American Journal of Physiology, 263, 659-664.
[33] Uysal, M., Seckin, S., Kocak-Toker, N. and Oz, H. (1989) Increased hepatic lipid peroxidation in aged mice. Mechanisms of Ageing and Development, 48, 85-89.
[34] Martins, D.B., Mazzanti, C.M., Franca, R.T., Pagnoncelli, M., Costa, M.M., De Souza, E.M., Goncalves, J., Spanevello, R., Schmatz, R., Da Costa, P., Mazzanti, A., Beckmann, D.V., Cecimda, S., Schetinger, M.R. and Lopes, S.T. (2012) 17-β estradiol in the actylcholinesterase activity and lipid peroxidation in the brain and blood of ovariectomized adult and middle-aged rats. Life Sciences, 90, 351-359.
[35] Rodriguez, M.M.A. and Ruiz, T. (1992) Homeostasis between lipid peroxidation and antioxidant enzymes activties in health human aging. Mechanisms of Ageing and Development, 66, 213-222.
[36] Subbiah, M.T., Kessel, B., Agrawal, M., Rajan, R., Abplanalp, W. and Rymaszewski, Z. (1993) Antioxidant potential of specific estrogens on lipid peroxidation. The Journal of Clinical Endocrinology & Metabolism, 77, 1095-1097.
[37] Vina, J., Sastre, J., Pallardo, F. and Borras, C. (2003) Mitochondrial theory of aging: Importance to explain why females live longer than males. Antioxidants & Redox Signaling, 5, 549-556.

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