AAR  Vol.2 No.4 , November 2013
Effects of tachykinin neuropeptide NKB and Aβ (25-35) on antioxidant enzymes status in 17β estradiol treated aging female rats

Aging is the leading risk factor for neurodegenerative diseases and oxidative stress involved in the pathophysiology of these diseases. These changes increase during menopausal condition in females when the level of estradiol is decreased. The aim of the present study was to determine the effect of tachykinin neuropeptide, Neurokinin B (NKB) and Amyloid beta fragment Aβ (25 - 35) on 17β estradiol (E2) treated aging female rat synaptosomes of different age groups. Aging brain functions were assayed by measuring the activities of antioxidant enzymes—superoxide dismutase (SOD) and monoamine oxidase (MAO) with neuropeptides. An in-vitro incubation of Aβ (25 - 35) in E2 treated brain synaptosomes showed toxic effects on all the parameters. However, NKB and NKB combined with Aβ (25 35) showed stimulating effects in E2 treated rat brain synaptosomes. In the present study, an increase in activity of SOD and decrease in the level of MAO, in the presence of NKB and combined NKB and Aβ in E2 treated brain synaptosomes of aging rats. This study elucidates that treatment of NKB and Aβ with E2 incombination exerts more protective influence than their individual application, against excitotoxicity in age related changes.

Cite this paper
Jha, R. , Mahdi, A. , Pandey, S. , Baquer, N. and Cowsik, S. (2013) Effects of tachykinin neuropeptide NKB and Aβ (25-35) on antioxidant enzymes status in 17β estradiol treated aging female rats. Advances in Aging Research, 2, 137-143. doi: 10.4236/aar.2013.24020.
[1]   Abrass, I.B. (1990) The biology and physiology of aging. Western Journal of Medicine, 153, 641-645.

[2]   Bodis, W.I., Chang, E., Ghilardi, M.F., Glover, A., Onfrj, M., Pasik, P. and Samson, Y. (1991) Acetyl-Levocarnitine protect against MPTP-induced Parkinsonism in primates. Journal of Neural Transmission—Parkinson’s Disease and Dementia Section, 3, 63-72. http://dx.doi.org/10.1007/BF02251137

[3]   Baquer, N.Z., Taha, A., Kumar, P., McLean, P., Cowsik, S.M., Kale, R.K., Singh, R. and Sharma, D. (2009) A metabolic and functional overview of brain aging linked to neurological disorders. Biogerontology, 10, 377-413. http://dx.doi.org/10.1007/s10522-009-9226-2

[4]   Brann, D.W., Krishnan, D., Chandramohan, W., Virendra, B.M. and Mohammad, M.K. (2007) Neurotrophic neuroprotective actions of estrogen: Basic mechanism and clinical implications. Steroids, 72, 381-405. http://dx.doi.org/10.1016/j.steroids.2007.02.003

[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. http://dx.doi.org/10.1016/j.exger.2011.02.008

[6]   Moorthy, K., Yadav, S.U.C., Mantha, A.K., Cowsik, S.M., Sharma, D. and Baquer, N.Z. (2004) Effect of estradiol and progesterone treatment on lipid profile in naturally menopausal rats from different age groups. Biogerontology, 5, 1-9. http://dx.doi.org/10.1007/s10522-004-3190-7

[7]   Gronemeyer, H., Gustafsson, J.A. and Laudet, V. (2004) Principles for modulation of the nuclear receptor superfamily. Nature Reviews Drug Discovery, 3, 950-964. http://dx.doi.org/10.1038/nrd1551

[8]   Spencer, J.L., Waters, E.M., Romeo, R.D., Wood, G.E., Millner, T.A. and McEwen, B.S. (2008) Uncovering the mechanism of estrogen effects on hippocampal function. Frontiers in Neuroendocrinology, 29, 219-237. http://dx.doi.org/10.1016/j.yfrne.2007.08.006

[9]   Garcia-Segura, L.M., Azcoitia, I. and DonCarlos, L.L. (2001) Neuroprotection by estradiol. Progress in Neurobiology, 63, 29-60. http://dx.doi.org/10.1016/S0301-0082(00)00025-3

[10]   Compton, J., Van Amelsvoort, T. and Declan, M. (2003) HRT and its effect on normal aging of the brain and dementia. Journal of Clinical Pharmacology, 52, 647-653.

[11]   Henderson, V.W. (2010) Action of estrogens in the aging brain: dementia and cognitive aging. Biochimica et Biophysica Acta, 1800, 1077-1083. http://dx.doi.org/10.1016/j.bbagen.2009.11.005

[12]   Dobson, C.M. (2003) Protein folding and misfolding. Nature, 426, 884-890.

[13]   Hung, L.W., Ciccotosto, G.D., Giannakis, E., Tew, D.J., Perez, K., Masters, C.L., Cappai, R., Wade, J.D. and Barnham, K.J. (2008) Amyloid-beta peptide (Abeta) neurotoxicity is modulated by the rate of peptide aggregation: Abeta dimers and trimers correlate with neurotoxicity. The Journal of Neuroscience, 28, 11950-11958. http://dx.doi.org/10.1523/JNEUROSCI.3916-08.2008

[14]   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. http://dx.doi.org/10.1016/j.tips.2003.11.005

[15]   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. http://dx.doi.org/10.2174/0929867043364748

[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. http://dx.doi.org/10.1016/0306-3623(85)90088-6

[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. http://dx.doi.org/10.1007/s10522-005-6043-0

[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. http://dx.doi.org/10.1007/s10522-005-6044-z

[19]   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.

[20]   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.

[21]   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. http://dx.doi.org/10.1023/B:BGEN.0000038026.89337.02

[22]   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. http://dx.doi.org/10.1111/j.1471-4159.1982.tb11475.x

[23]   Marklund, S. and Marklund, G. (1974) Involvement of the super anion radicals in the autoxidation of pyrogollol and a convenient assay for superoxide dismutase. European Journal of Biochemistry, 47, 469-474. http://dx.doi.org/10.1111/j.1432-1033.1974.tb03714.x

[24]   Catravas, G.N., Takenaga, J. and McHale, C.G. (1977) Effect of chronic administration of morphine on monoamine oxidase activity in discrete regions of the brain of rats. Biochemical Pharmacology, 26, 211-214. http://dx.doi.org/10.1016/0006-2952(77)90305-7

[25]   Bradford, M.M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72, 248-254. http://dx.doi.org/10.1016/0003-2697(76)90527-3

[26]   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.

[27]   Varadarajan, S., Kanski, J., Aksenova, M., Lauderback, C. and Butterfield, D.A. (2001) Different mechanisms of oxidative stress and neurotoxicity for Alzheimer’s A beta (1 42) and A beta (25 35). Journal of the American Chemical Society, 123, 5625-5631. http://dx.doi.org/10.1021/ja010452r

[28]   Song, W., Zhou, L.J., Zheng, S.X. and Zhu, X.Z. (2000) Amyloid-beta 25-35 peptide induces expression of monoamine oxidase B in cultured rat astrocytes. Acta Pharmacologica Sinica, 21, 557-563.