<strong>Secoisolariciresinol Reduces Behavioral Despair and Regulates Hippocampal BDNF Expression in Ovariectomized Mice</strong>

Abstract

Abstract:Objective: To investigate the antidepressant-like effect and the possible mechanism of Secoisolariciresinol (SECO) in ovariectomized (OVX) mice.Methods: OVX mice were used as a menopausal animal model and tail suspension and forced swimming tests were conducted to measure the effects of SECO on behavioral despair. The expression levels of brain-derived neurotrophic factor (BDNF) mRNA and protein were measured by real-time PCR, Western blot analysis and immunofluorescence. In addition, Akt and pAkt were tested by Western blot analysis and BrdU-labeled cells were observed by immunofluorescence.Results: SECO (10 and 20 mg/kg, p.o. ) significantly reduced the immobility duration of OVX mice in both forced swimming and tail suspension tests. Administration of SECO significantly increased BDNF levels in hippocampus. Moreover, this study demonstrated that SECO increased BDNF immunoreactivity in hippocampal CA1, CA3 and DG pyramidal neurons, and BrdU-labeled cell number in the DG subfield. SECO also significantly increased the phosphorylation of Akt.Conclusion: SECO has the potential to treat depression in menopausal women which may be attributed to BDNF-mediated PI3K/Akt signaling pathway.

Key words:Secoisolariciresinol (SECO),Ovariectomized mice,Forced swimming,Tail suspension,Brain-derived neurotrophic factor (BDNF)

YAO Guang-Yin, JI Dan-Yang, ZHOU Wei-Dong, YAO Hai-Yan, KU Bao-Shan, YANG Dong-Hui.Secoisolariciresinol Reduces Behavioral Despair and Regulates Hippocampal BDNF Expression in Ovariectomized Mice[J]. Acta Neuropharmacologica, 2013, 3(2): 13-25.

References

[1] Meir Steiner, Edward Dunn, Leslie Born. Hormones and mood: from menarche to menopause and beyond[J]. J Affect Disord, 2003, 74(1):67-83.

[2] Berecki-Gisolf J, Begum N, Dobson A J. Symptoms reported by women in midlife: menopausal transition or aging? [J] Menopause, 2009, 16(5):1021-1029.

[3] Susan E Gilbert Evans, Lori E Ross, Edward M Sellers, et al. 3alpha-reduced neuroactive steroids and their precursors during pregnancy and the postpartum period[J]. Gynecol Endocrinol, 2005, 21(5):268-279.

[4] Mehta D, Newport D J, Frishman G, et al. Early predictive biomarkers for postpartum depression point to a role for estrogen receptor signaling[J]. J Psychological medicine, 2014, 5: 1-14.

[5] Marie K Osterlund, Michael Robin Witt, Jan-Ake Gustafsson. Estrogen action in mood and neurodegenerative disorders: estrogenic compounds with selective properties-the next generation of therapeutics[J]. Endocrine, 2005, 28(3):235-242.

[6] Andrea J Rapkin, Judith A Mikacich, Babak Moatakef-Imani, et al. The clinical nature and formal diagnosis of premenstrual, postpartum, and peri-menopausal affective disorders[J]. Curr Psychiatry Rep, 2002, 4(6):419-428.

[7] Jessica Zonana, Jack M Gorman. The neurobiology of postpartum depression[J]. CNS Spectr, 2000, 10(10):792-799, 805.

[8] Lasiuk G C, Hegadoren K M. The effects of estradiol on central serotonergic systems and its relationship to mood in women[J]. Biol Res Nurs, 2007, 9(2):147-60.

[9] Barbara L Parry, Charles J Meliska, L Fernando Martinez, et al. Menopause: neuroendocrine changes and hormone replacement therapy[J]. J Am Med Womens Assoc, 2004, 59(2):135-145.

[10] Grady D, Gebretsadik T, Kerlikowske K, et al. Hormone replacement therapy and endometrial cancer risk: a meta-analysis[J]. Obstet Gynecol, 1995, 85(2):304-313.

[11]Song Q W, Wang X G. Progress in research on PE for prevention and treatment of perimenopausal syndrome[J]. Foreign Medical Science (Section of Maternal and Child Health), 2004, 15:124-125.

[12] Charlotta Dabrosin, Chen Jian-min, Wang Linda, et al. Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts[J]. Cancer Lett, 2002, 185(1):31-37.

[13] Franziska Kramer Birkved, Alicja Mortensen, Jose L Peñalvo, et al. Investigation into the cancer protective effect of flaxseed in Tg. NK (MMTV/c-neu) mice, a murine mammary tumor model[J]. Genes Nutr, 2011, 6(4):403-411.

[14] Yasin Tülüce, Halil Ozkol, Ismail Koyuncu. Photoprotective effect of flax seed oil (Linumusitatissimum L.) against ultraviolet C-induced apoptosis and oxidative stress in rats[J]. ToxicolInd Health, 2012, 28(2):99-107.

[15] Wang Ying-feng, Xu Zhi-kun, Yang Dong-hui, et al. The antidepressant effect of secoisolariciresinol, a lignan-type phytoestrogen constituent of flaxseed, on ovariectomizedmice[J]. J Nat Med, 2013, 67(1):222-227.

[16] Ronald S Duman, George K Aghajanian. Neurobiology of Rapid Acting Antidepressants: Role of BDNF and GSK-3β[J]. J Neuropsychopharmacology, 2014, 39(1): 233-233

[17] Joanna L Spencer-Segal, Elizabeth M Waters, Kevin G Bath, et al. Distribution of phosphorylated TrkB receptor in the mouse hippocampal formation depends on sex and estrous cycle stage[J]. J Neurosci, 2011, 31(18):6780-6790.

[18] Tadahiro Numakawa, Misty Richards, Shingo Nakajima, et al. The role of brain-derived neurotrophic factor in comorbid depression: possible linkage with steroid hormones, cytokines, and nutrition[J]. J Frontiers in psychiatry, 2014, 5:136.

[19] Helen E Scharfman, Thomas C Mercurio, Jeffrey H Goodman, et al. Hippocampal excitability increases during the estrous cycle in the rat: a potential role for brain-derived neurotrophic factor[J]. J Neurosci, 2003, 23(37):11641-11652.

[20] Alicia A Walf, Cheryl A Frye. Antianxiety and antidepressive behavior produced by physiological estradiol regimen may be modulated by hypothalamic-pituitary-adrenal axis activity[J]. J Neuropsychopharmacology, 2005, 30(7):1288-1301.

[21] Naoko Bekku, Hiroyuki Yoshimura. Animal model of menopausal depressive-like state in female mice: prolongation of immobility time in the forced swimming test following ovariectomy[J]. Psychopharmacology (Berl), 2005, 183(3):300-307.

[22] Lucien Steru, Raymond Chermat, Bernard Thierry, et al. The tail suspension test: a new method for screening antidepressants in mice[J]. Psychopharmacology (Berl), 1985, 85(3):367-370.

[23] Porsolt R D, Le Pichon M, Jalfre M. Depression: a new animal model sensitive to antidepressant treatments[J]. Nature, 1977, 266(5604):730-732.

[24] Xu Ying, Ku Bao-shan, Yao Hai-yan, et al. The effects of curcumin on depressive-like behaviors in mice[J]. Eur J Pharmacol, 2005, 518(1):40-46.

[25] Vivien K Burt, Kira Stein. Epidemiology of depression throughout the female life cycle[J]. J Clin Psychiatry, 2002, 63 (Suppl 7):9-15.

[26] Ronald C Kessler. Epidemiology of women and depression[J]. J Affect Disord, 2003, 74(1):5-13.

[27] Miki Bloch, Robert C Daly, David R Rubinow. Endocrine factors in the etiology of postpartum depression[J]. Compr Psychiatry, 2003, 44(3):234-246.

[28] Heidi D Nelson, Linda L Humphrey, Peggy Nygren, et al. Postmenopausal hormone replacement therapy: scientific review[J]. JAMA, 2002, 288(7):872-881.

[29] Valerie Beral, Million Women Study Collaborators, Bull D, et al. Ovarian cancer and hormone replacement therapy in the Million Women Study[J]. Lancet, 2007, 369:1703-1710.

[30] Amnon Brzezinski, Ayelet Debi. Phytoestrogens: the "natural" selective estrogen receptor modulators? [J]. Eur J Obstet Gynecol Reprod Biol, 1999, 85(1):47-51.

[31] Ayman A Ewies. Phytoestrogens in the management of the menopause: up-to-date[J]. Obstet Gynecol Surv, 2002, 57(5):306-313.

[32] Susan R Sturgeon, Stella L Volpe, Elaine Puleo, et al. Effect of flaxseed consumption on urinary levels of estrogen metabolites in postmenopausal women[J]. Nutr Cancer, 2010, 62(2):175-180.

[33] Helena M Barros, Maristela Ferigolo. Ethopharmacology of imipramine in the forced-swimming test: gender differences[J]. Neurosci Biobehav Rev, 1998, 23:279-286.

[34] Benoit Petit-Demouliere, Franck Chenu, Michel Bourin. Forced swimming test in mice: a review of anti-depressant activity[J]. Psychopharmacology (Berl), 2005, 177(3):245-255.

[35] Naoko Bekku, Hiroyuki Yoshimura, Hiroaki Araki. Factors producing a menopausal depressive-like state in mice following ovariectomy[J]. Psychopharmacology (Berl), 2006, 187(2):170-180.

[36]Bekku N, Yoshimura H. Animal model of menopausal depressive-like state in female mice: prolongation of immobility time in the forced swimming test following ovariectomy[J]. Psychopharmacology (Berl), 2005,183:300-307.

[37] Liisa A Galea, Jennifer K Wide, Alasdair M Barr. Estradiol alleviates depressive-like symptoms in a novel animal model of post-partum depression[J]. Behav Brain Res, 2001, 122(1):1-9.

[38] Erin C Stoffel, Rebecca M Craft. Ovarian hormone withdrawal-induced "depression" in female rats[J]. Physiol Behav, 2004, 83(3):505-513.

[39] Joanna L Spencer-Segal, Elizabeth M Waters, Kevin G Bath, et al. Distribution of phosphorylated TrkB receptor in the mouse hippocampal formation depends on sex and estrous cycle stage[J]. J Neurosci, 2011, 31(18):6780-6790.

[40] Helen E Scharfman, Thomas C Mercurio, Jeffrey H Goodman, et al. Hippocampal excitability increases during the estrous cycle in the rat: a potential role for brain-derived neurotrophic factor[J]. J Neurosci, 2003, 23(37):11641-11652.

[41] Clive R Bramham, Debabrata Panja. BDNF regulation of synaptic structure, function, and plasticity[J]. J Neuropharmacology, 2014, 76(Pt: C): 601-602.

[42] Kaoru Sato, Tatsuhiro Akaishi, Norio Matsuki, et al. beta-Estradiol induces synaptogenesis in the hippocampus by enhancing brain-derived neurotrophic factor release from dentate gyrus granule cells[J]. Brain Res, 2007, 1150:108-120.

[43] Helen E Scharfman, Tana M Hintz, Juan Gomez, et al. Changes in hippocampal function of ovariectomized rats after sequential low doses of estradiol to simulate the preovulatory estrogen surge[J]. Eur J Neurosci, 2007, 26(9):2595-2612.

[44] Melinda K Jezierski, Farida Sohrabji. Estrogen enhances retrograde transport of brain-derived neurotrophic factor in the rodent forebrain[J]. Endocrinology, 2003, 144(11):5022-5029.

[45] Carol J Haggans, Elsa J Travelli, William Thomas, et al. The effect of flaxseed and wheat bran consumption on urinary estrogen metabolites in premenopausal women[J]. Cancer Epidemiol Biomarkers Prev, 2000, 9(7):719-725.

[46] Charlotte Carreau, Gilles Flouriot, Catherine Bennetau-Pelissero, et al. Enterodiol and enterolactone, two major diet-derived polyphenol metabolites have different impact on ER alpha transcriptional activation in human breast cancer cells[J]. J Steroid Biochem Mol Biol, 2008, 110(1-2): 176-185.

[47] Kenji Hashimoto. Brain-derived neurotrophic factor (BDNF) and its precursor pro-BDNF as diagnostic biomarkers for major depressive disorder and bipolar disorder[J]. J European archives of psychiatry and clinical neuroscience, 2015(1): 83-84.

[48] Zhang Qi, Liu Gang, Wu Yi, et al. BDNF promotes EGF-induced proliferation and migration of human fetal neural stem/progenitor cells via the PI3K/Akt pathway[J]. Molecules, 2011, 16(12):10146-10156.

Secoisolariciresinol Reduces Behavioral Despair and Regulates Hippocampal BDNF Expression in Ovariectomized Mice

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