Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Japan.
J Pharmacol Sci. 2012;120(2):89-97. doi: 10.1254/jphs.12115fp. Epub 2012 Sep 6.
We have recently found that combination of ovariectomy (OVX) and chronic restraint stress causes cognitive dysfunction and reduces hippocampal CA3 neurons in female rats and mice and that estrogen replacement and chronic treatment with Ginkgo biloba extract EGb 761 suppress the OVX/stress-induced behavioral and morphological changes. In this study, we examined the effect of placental extract on the memory impairment and neuromorphological change in OVX/stress-subjected mice. Female Slc:ICR strain mice were randomly divided into four groups: vehicle-treated OVX, porcine placental extract (120 and 2160 mg/kg)-treated OVX, and sham-operated control groups. Two weeks after surgical operation, OVX mice underwent restraint stress for 21 days (6 h/day), and all animals were then subjected to a contextual fear conditioning test followed by morphological examination by Nissl staining. Placental extract was orally administered once daily until the behavioral analysis was carried out. Chronic treatment with both doses of placental extract improved the OVX/stress-induced fear memory impairment and Nissl-positive cell loss of the hippocampal CA3 region, although it did not affect the loss of bone mineral density and increase in body weight after OVX. These results have important implications for the neuroprotective and cognition-enhancing effects of placental extract in postmenopausal women.
我们最近发现,卵巢切除术(OVX)和慢性束缚应激的组合会导致雌性大鼠和小鼠认知功能障碍,并减少海马 CA3 神经元,而雌激素替代和银杏叶提取物 EGb 761 的慢性治疗可以抑制 OVX/应激引起的行为和形态变化。在这项研究中,我们研究了胎盘提取物对 OVX/应激小鼠记忆障碍和神经形态变化的影响。雌性 Slc:ICR 品系小鼠随机分为四组: vehicle(溶剂)处理的 OVX、猪胎盘提取物(120 和 2160 mg/kg)处理的 OVX 和假手术对照组。手术后 2 周,OVX 小鼠接受 21 天的束缚应激(每天 6 小时),然后所有动物接受情景恐惧条件反射测试,随后进行尼氏染色的形态学检查。胎盘提取物每天口服一次,直到进行行为分析。两种剂量的胎盘提取物均可改善 OVX/应激引起的恐惧记忆障碍和海马 CA3 区尼氏阳性细胞丢失,尽管它不影响 OVX 后骨密度的丧失和体重的增加。这些结果对胎盘提取物在绝经后妇女中的神经保护和认知增强作用具有重要意义。