Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-4291, USA.
Neurobiol Aging. 2012 Apr;33(4):708-19. doi: 10.1016/j.neurobiolaging.2010.06.008. Epub 2010 Jul 31.
Brain-derived neurotrophic factor (BDNF) has emerged as a possible broad-spectrum treatment for the plasticity losses found in rodent models of human conditions associated with memory and cognitive deficits. We have tested this strategy in the particular case of ovariectomy. The actin polymerization in spines normally found after patterned afferent stimulation was greatly reduced, along with the stabilization of long-term potentiation, in hippocampal slices prepared from middle-aged ovariectomized rats. Both effects were fully restored by a 60-minute infusion of 2 nM BDNF. Comparable rescue results were obtained after elevating endogenous BDNF protein levels in hippocampus with 4 daily injections of a short half-life ampakine (positive modulator of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate [AMPA]-type glutamate receptors). These results provide the first evidence that minimally invasive, mechanism-based drug treatments can ameliorate defects in spine plasticity caused by depressed estrogen levels.
脑源性神经营养因子 (BDNF) 已成为一种可能的广谱治疗方法，可用于治疗与记忆和认知缺陷相关的人类疾病的啮齿动物模型中发现的可塑性丧失。我们在卵巢切除的特殊情况下对此策略进行了测试。在从中年去卵巢大鼠制备的海马切片中，与模式传入刺激后通常发现的正常棘突中的肌动蛋白聚合相比，长时程增强的稳定性大大降低。BDNF 的 60 分钟输注完全恢复了这两种作用。通过 4 次每日注射半衰期短的ampakine（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸[AMPA]型谷氨酸受体的正调节剂）来提高海马中的内源性 BDNF 蛋白水平，可获得类似的挽救结果。这些结果首次提供了证据，证明微创、基于机制的药物治疗可以改善因雌激素水平降低而导致的脊柱可塑性缺陷。
