Effects of Puerarin on Learning-Memory and Amino Acid Transmitters of Brain in Ovariectomized Mice

Abstract

In the present study, the protective effects of puerarin (Pur) on learning and memory in ovariectomized mice were investigated. One week after ovariectomy (Ovx) or sham operation, female mice were given a 4-week treatment of Pur (50 or 100 mg/kg, i. p.) or estradiol benzoate (EB, 1 or 5 μg/day, i. p.). The results showed that, following treatment with 50 or 100 mg/kg Pur in Ovx mice, the training times for achieved learning criterion in a Y-maze declined by 11.8 % and 17.8 % (P > 0.05 and P < 0.05), and that memory retention increased by 23.3 % and 28.3 % (P < 0.05 and P < 0.05), respectively. In addition, the prolonged escape latency of platform finding in a water maze was shortened by 15.5 % and 23.8 % (P < 0.05 and P < 0.05). After a behavior test, the levels of glutamate (Glu) and GABA in the frontal cortex and hippocampus were assessed using high-performance liquid chromatography (HPLC). The results showed that 100 mg/kg Pur normalized the levels of Glu and GABA in the hippocampus of Ovx mice, while the Glu level was significantly elevated from 24.1 ± 4.5 to 27.9 ± 3.5 mg/g protein (P < 0.05), and GABA was decreased from 5.64 ± 1.06 to 4.73 ± 0.85 mg/g protein (P < 0.05). The results indicated that Pur possessed phytoestrogen activity, and long-term treatment of Pur ameliorated learning and memory deficits of Ovx mice through affecting the activity of the glutamatergic/GABAergic system in the hippocampus.

Puerarin - estrogen - ovariectomy - learning and memory - amino acid transmitters

References

• 1 Henderson V W. Estrogen, cognition, and a woman's risk of Alzheimer's disease.  Am J Med. 1997;  103 11S-18
• 2 Frick K M, Fernandez S M, Bulinski S C. Estrogen replacement improves spatial reference memory and increases hippocampal synaptophysin in aged female mice.  Neuroscience. 2002;  115 547-58
• 3 Segal M, Murphy D. Estrogen induces formation of dendritic spines in hippocampal neurons: functional correlates.  Horm Behav. 2001;  40 156-9
• 4 Foy M R, Xu J, Xie X, Brinton R D, Thompson R F, Berger T W. 17.-Estradiol enhances NMDA receptor-mediated EPSPs and long-term potentiation.  J Neurophysiol. 1999;  81 925-9
• 5 Gibbs R B. Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats.  Neurobiol Aging. 2000;  21 107-16
• 6 Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: a meta-analysis.  Obstet Gynecol. 1995;  85 304-13
• 7 Fitzpatrick L A. Soy isoflavones: hope or hype.  J Eur menopause Maturitas. 2003;  44 S21-29
• 8 Zheng G L, Zhang X Y, Zheng J W, Meng Q C, Zheng D S. Estrogen-like effects of puerarin and total isoflavones from Pueraria lobata .  J Chin Med Materials. 2002;  25 566-8
• 9 Zheng G L, Zhang X Y, Fang X L, Peng X Y, Gong W G, Zheng X X. Effects of total isoflavones of Pueraria DC. on bone mineral density and bone strength in ovariectomized rats.  Chin Traditional Herbal Drugs. 2001;  32 422-5
• 10 Woolley C S, Weiland N G, McEwen B S, Schwartzkroin P A. Estradiol increases the sensitivity of hippocampal CA1 pyramidal cells to NMDA receptor-mediated synaptic input: Correlation with dendritic spine density.  J Neurosci. 1997;  17 1848-59
• 11 Murphy D D, Cole N B, Greenberger V, Segal M. Estradiol increases dendritic spine density by reducing GABA neurotransmission in hippocampal neurons.  J Neurosci. 1998;  18 2550-9
• 12 Myhrer T. Neurotransmitter systems involved in learning and memory in the rat: a meta-analysis based on studies of four behavioral tasks.  Brain Res Rev. 2003;  41 268-87
• 13 Crawley J N. Exploratory behavior model of anxiety in mice.  Neurosci Biobehav Rev. 1985;  9 37-44
• 14 Xu X H, Zhao T Q. Effects of puerarin on D-galactose-induced memory deficits in mice.  Acta Pharmacol Sin. 2002;  23 587-90
• 15 Wilson I A, Puolivali J, Heikkinen T, Riekkinen P J. Estrogen and NMDA receptor antagonism: effects upon reference and working memory.  Eur J Pharmacol. 1999;  381 93-9
• 16 Franklin K BJ, Paxinos G. The mouse brain in stereotaxic coordinates. San Diego; Academic Press 1997: pp 10-54
• 17 Zhang M, Ning G M, Shou C H, Lu Y J, Hong D H, Zheng X X. Inhibitory effect of Jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus.  Planta Medica. 2003;  69 692-5
• 18 Mitchell J L, Cruickshanks K J, Klein B E, Palta M, Nondahl D M. Postmenopausal hormone therapy and its association with cognitive impairment.  Arch Intern Med. 2003;  163 2485-90
• 19 Farr S A, Banks W A, Morley J E. Estradiol potentiates acetycholine and glutamate-mediated post-trial memory processing in the hippocampus.  Brain Res. 2000;  864 263-9
• 20 Hsieh M T, Kuo L H, Tsai F H, Wang W H, Wu C RE. ffects of puerarin on scopolamine-, mecamylamine-, p-chloroamphetamine- and dizocilpine-induced inhibitory avoidance performance impairment in rats.  Planta Medica. 2002;  68 901-5
• 21 Li X L, Sun S G. Experimental research on the protective effect of puerarin to Parkinson disease.  J Brain Nervous Disease. 2002;  10 7-9
• 22 Markham J A, Pych J C, Juraska J M. Ovarian hormone replacement to aged ovariectomized female rats benefits acquisition of the Morris water maze.  Horm Behav . 2002;  42 284-93
• 23 Cos P, Bruyne T D, Apers S, Berghe D V, Pieters L, Vlietinck A J. Phytoestrogens: Recent developments.  Planta Medica. 2003;  69 692-5