Luteinizing hormone: Evidence for direct action in the CNS.
Luteinizing hormone: Evidence for direct action in the CNS.
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DOI：
10.1016/j.yhbeh.2015.06.020
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发表时间：
2015-11
影响因子：
3.5
通讯作者：
Casadesus G
中科院分区：
文献类型：
--
作者：
Blair JA;Bhatta S;McGee H;Casadesus G
衰老，尤其是在更年期期间导致的激素功能失调，在认知能力下降以及神经退行性疾病的进展和发展中起着重要作用。下丘脑 - 垂体 - 性腺（HPG）轴长期以来一直被认为与行为和神经元形态的变化有关。最值得注意的是，雌激素通过多种不同机制已被证明对健康的大脑有益。最近，黄体生成素（LH）因其在中枢神经系统中的作用而成为进一步研究的对象。其依据是LH和LH受体在大脑中均有表达，且血清LH水平与认知缺陷和阿尔茨海默病（AD）的发病率相关。对LH在认知和AD方面的研究主要集中在评估这种肽下调的影响。相关文献表明，通过多种药物干预降低外周LH可减轻卵巢切除和AD模型中的认知缺陷。然而，很少有研究探究LH对神经元和神经胶质细胞的直接作用。在此我们总结了黄体生成素在调节认知中的作用，并提出了大脑LH在这一过程中所起作用的潜在机制。
在老年雌性大脑中，卵巢切除术后的雌激素替代并不能改善认知功能或相关的潜在机制，如树突棘密度的变化。降低卵巢切除术后或更年期期间激增的外周LH水平的药物可挽救卵巢切除相关的认知功能障碍，增加与突触可塑性相关的信号事件。LH受体定位于与认知相关的区域，其功能在功能和可塑性层面均有描述。脑源性LH蛋白水平存在于与认知相关的区域，且卵巢切除会使其降低。通过降低外周LH水平的药物可使这些水平恢复正常，并且脑LH的这种正常化与神经可塑性和认知改善的标志物呈正相关。
Hormonal dysfunction due to aging, especially during menopause, plays a substantial role in cognitive decline as well as the progression and development of neurodegenerative diseases. The hypothalamic-pituitary-gonadal (HPG) axis has long been implicated in changes in behavior and neuronal morphology. Most notably, estrogens have proven beneficial in the healthy brain through a host of different mechanisms. Recently, luteinizing hormone (LH) has emerged as a candidate for further investigation for its role in the CNS. The basis of this is that both LH and the LH receptor are expressed in the brain, and serum levels of LH correlate with cognitive deficits and Alzheimer's disease (AD) incidence. The study of LH in cognition and AD primarily focuses on evaluating the effects of downregulation of this peptide. This literature has shown that decreasing peripheral LH, through a variety of pharmacological interventions, reduces cognitive deficits in ovariectomy and AD models. However, few studies have researched the direct actions of LH on neurons and glial cells. Here we summarize the role of luteinizing hormone in modulating cognition, and we propose a mechanism that underlies a role for brain LH in this process. In the aged female brain estrogen replacement after ovariectomy does not improve cognitive function or associated underlying mechanisms such as dendritic spine density changes. Drugs that reduce peripheral levels of LH, which surge after ovariectomy or during menopause, rescue ovariectomy-dependent cognitive dysfunction, increases signaling events associated with synaptic plasticity. The LH receptor is localized to cognition-associated areas and its functionality is described both at a level of function and plasticity. Brain-derived LH protein levels are present in cognition associated areas and reduced by ovariectomy. These levels are normalized by drugs that reduce peripheral LH levels and this normalization of brain-LH positively correlates with markers of neuroplasticity and cognitive improvement.