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ANXIOLYTIC-LIKE EFFECTS OF BIOTECHNOLOGICAL PREPARATION ROPREN- IN ?-AMYLOID-(25-35) RAT MODEL OF ALZHEIMER'S DISEASE IN FEMALE RATS WITH EXPERIMENTAL MODEL OF MENOPAUSE
Abstract
The global population of menopausal women is on the rise and expected to increase from 470 million in 1990 to 1.2 billion by the year 2030. Most of them suffer from postmenopausal symptoms, such as hot flushes, tender breasts, vaginal dryness, reduced bone mineral density, cognitive deterioration and neuropsychiatric disorders such as different mood disturbances and cognitive impairments including AlzheimerпїЅs disease (AD). Considering the wide use of complementary and alternative medications such as bioactive supplements in menopausal patients and our insufficient knowledge about the interaction between hormone replacement therapy and bioactive supplements, investigating the subject from a preclinical experimental studies seems very beneficial. RoprenпїЅ can be such candidate substance for treatment of AD in women with an imbalance of estrogen. RoprenпїЅ substance (pure polyprenols) was isolated from the green verdure of Picea abies (L.) Karst. Nowadays, polyprenols have been extensively studied as multifunctional agents for the prevention and treatment of many neurological diseases. The present preclinical study was designed to examine the effects of prolonged RoprenпїЅ administration (8.6 mg/kg, per os, 28 days, once daily) on anxiety-like behavior in a ?-amyloid (25-35) rat model of Alzheimer's disease following long-term ovariectomy (12 weeks). The experimental model was created by intracerebroventricular injection of ?-amyloid (25-35) into ovariectomized (OVX) rats and OVX rats with 17?-estradiol (17?-E2, 5.0 ?g/rat, subcutaneously, once daily, 28 days) supplementation. RoprenпїЅ was administered to the OVX rats and OVX rats treated with 17?-E2. Anxiety-like behavior was assessed in the elevated plus maze and light-dark test (LDT), as well a spontaneous locomotor activity was assessed using the open field test. The corticosterone and estradiol levels in the blood serum before and after EPM and LDT tests were measured in all experimental groups. Treatment with RoprenпїЅ significantly increased the time spent into the open arms of OVX rats with ?-amyloid (25-35)-induced amnesia in the EPM and LDT tests. Co-administration of RoprenпїЅ with 17?-E2 exerted a markedly synergistic anxiolytic-like effect in the OVX rats with ?-amyloid (25-35)-induced amnesia on the same models of anxiety-like behavior testing. RoprenпїЅ administered alone or together with 17?-E2 significantly enhanced crossing, frequency of rearing and grooming of the OVX rats with ?-amyloid (25-35)-induced amnesia in the open field test. Moreover, RoprenпїЅ administered alone or together with 17?-E2 significantly increased lower estradiol levels in the blood serum of OVX rats with ?-amyloid (25-35)-induced amnesia. These results indicate that RoprenпїЅ has a marked anxiolytic-like effect in the experimental model of AlzheimerпїЅs disease in female rats with long-term estrogen deficiency.
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Santoro N., Epperson C.N., Mathews S.B. Menopausal Symptoms and their Management. Endocrinol. Metab. Clin North Am vol. 44, pp. 497-515, 2015.
Maki P.M., Freeman E.W., Greendale G.A., Henderson V.W., Newhouse P.A., Schmidt P.J., Scott N.F., Shively C.A., Soares C.N. Summary of the National Institute on aging-sponsored conference on depressive symptoms and cognitive complaints in the menopausal transition. Menopause, vol. 17, pp. 815-822, 2010.
Soares C.N. Depression in peri- and postmenopausal women: Prevalence, pathophysiology and pharmacological management. Drugs Aging, vol. 30, pp. 677-685, 2013.
Soares C.N., Almeida O.P., Joffe H., Cohen L.S. Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: A double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry, vol. 58, pp. 529-534, 2001.
Vedder L.C., Bredemann T.M., McMahon L.L. Estradiol replacement extends the window of opportunity for hippocampal function. Neurobiol Aging, vol. 35, pp. 2183- 2192, 2014.
Studd J., Nappi R.E. Reproductive depression. Gynecol Endocrinol, vol. 28 (Suppl. S1), pp. 42-45, 2012.
Soares, C.N., Maki, P.M. Menopausal transition, mood, and cognition: An integrated view to close the gaps. Menopause, vol. 17, pp. 812-814, 2010.
Salomone S., Caraci F., Leggio G.M., Fedotova J., Drago F., New pharmacological strategies for treatment of Alzheimer’s disease: focus on disease modifying drugs. Br J Clin Pharmacol, vol. 73, pp 504-517, 2012.
Weisenbach S.L., Boore L.A., Kales H.C., Depression and cognitive impairment in older adults. Curr Psychiatry Rep, vol. 14, pp 280-288, 2012.
Tsolaki M., Grammaticos P., Karanasou C., Balaris V., Kapoukranidou D., Kalpidis I., Petsanis K., Dedousi E., Serum estradiol, progesterone, testosterone, FSH and LH levels in postmenopausal women with Alzheimer’s dementia. Hell J Nucl Med, vol. 8, pp 39-42, 2005.
Choi D.-Y., Lee Y.-J. Hong J.T., Lee H.J., Antioxidant properties of natural polyphenols and their therapeutic potentials for Alzheimer’s disease. Brain Res Bull vol. 87, pp 144-153, 2012.
Bosee R., Di Paolo T. Dopamine and GABAA receptor imbalance after ovariectomy in rats: Model of menopause. J Psychiatr Neurosci, vol. 20, pp. 364-371, 1995.
Pellow S., File S.E. Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus maze: A novel test of anxiety in the rat. Pharmacol Biochem Behav, vol. 24, pp. 526-530, 1986.
Edinger K.L., Frye C.A. Sexual experience of male rats influences anxiety-like behavior and androgen levels. Physiol Behav, vol. 92, pp. 443-453, 2007.
Skorupinska-Tudek K., Wojcik J., Swiezewska E., Polyisoprenoid alcohols - recent results of structural studies. Chemical Records, vol. 8, pp 33-45, 2008.
Burger H. The menopausal transition - endocrinology. J. Sex. Med. vol. 5, pp. 2266- 2273, 2008.
Vera P.G., Rada G.C. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the women’s health initiative randomized controlled trial. Obstet. Gynecol. Syrv., vol. 57, pp. 750-752, 2002.
Anderson G.L., Limacher M., Assaf A.R., Bassford T., Beresford S.A., Black H. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA, vol. 291, pp. 1701-1712, 2004.
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