Department of Biological Sciences, Kent State University, Kent, OH, USA.
Department of Biological Sciences, Kent State University, Kent, OH, USA.
Neurobiol Aging. 2019 Jun;78:111-120. doi: 10.1016/j.neurobiolaging.2019.02.002. Epub 2019 Feb 13.
Ovariectomy (OVX), a menopause model, leads to cognition and neuronal plasticity deficits that are rescued by estrogen administration or downregulation of pituitary luteinizing hormone (LH). LH is present in the brain. However, whether LH levels differ across brain regions, change across reproductive stages, or whether brain-specific LHR signaling play a role in OVX-related cognitive and neuroplasticity losses is completely unknown. To address this, we measured brain LH in cycling and OVX C57Bl/6 across brain regions and determined whether OVX-related functional and plasticity deficits could be rescued by intracerebroventricular administration of the LHR agonist (hCG). Here, we show that while pituitary LH is increased in OVX, brain LH is decreased, primarily in spatial memory and navigation areas. Furthermore, intracerebroventricular hCG delivery after OVX rescued dendritic spine density and spatial memory. In vitro, we show that hCG increased neurite outgrowth in primary hippocampal neurons in a receptor-specific manner. Taken together, our data suggest that loss of brain LH signaling is involved in cognitive and plasticity losses associated with OVX and loss of ovarian hormones.
卵巢切除术（OVX）是一种绝经模型，会导致认知和神经元可塑性缺陷，而雌激素给药或下调垂体促黄体生成素（LH）可以挽救这些缺陷。LH 存在于大脑中。然而，大脑不同区域的 LH 水平是否不同，在生殖阶段是否会发生变化，或者大脑特异性 LHR 信号是否在 OVX 相关认知和神经可塑性丧失中发挥作用，目前还完全不清楚。为了解决这个问题，我们测量了循环和 OVX C57Bl/6 小鼠大脑中不同区域的脑 LH，并确定了脑室内给予 LHR 激动剂（hCG）是否可以挽救 OVX 相关的功能和可塑性缺陷。在这里，我们表明，虽然 OVX 后垂体 LH 增加，但脑 LH 减少，主要是在空间记忆和导航区域。此外，OVX 后脑室内给予 hCG 可挽救树突棘密度和空间记忆。体外，我们表明 hCG 以受体特异性方式增加原代海马神经元的神经突生长。总之，我们的数据表明，脑 LH 信号的丧失与 OVX 和卵巢激素丧失相关的认知和可塑性丧失有关。
