Philbert Sasha A, Xu Jingshu, Church Stephanie J, Unwin Richard D, Roncaroli Federico, Cooper Garth J S
Division of Cardiovascular Sciences, Centre for Advanced Discovery and Experimental Therapeutics, Faculty of Biology, Medicine and Health, School of Medical Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Division of Cancer Sciences, Stoller Biomarker Discovery Centre, Faculty of Biology, Medicine and Health, School of Medical Sciences, The University of Manchester, Manchester, United Kingdom.
Front Aging Neurosci. 2022 Jul 18;14:926463. doi: 10.3389/fnagi.2022.926463. eCollection 2022.
Vascular dementia (VaD) is the second most common cause of cognitive impairment amongst the elderly. However, there are no known disease-modifying therapies for VaD, probably due to incomplete understanding of the molecular basis of the disease. Despite the complex etiology of neurodegenerative conditions, a growing body of research now suggests the potential involvement of metal dyshomeostasis in the pathogenesis of several of the age-related dementias. However, by comparison, there remains little research investigating brain metal levels in VaD. In order to shed light on the possible involvement of metal dyshomeostasis in VaD, we employed inductively coupled plasma-mass spectrometry to quantify the levels of essential metals in VaD brain tissue ( = 10) and age-/sex-matched controls ( = 10) from seven brain regions. We found novel evidence for elevated wet-weight cerebral sodium levels in VaD brain tissue in six out of the seven regions analyzed. Decreased cerebral-potassium levels as well as increased Na/K ratios (consistent with high tissue sodium and low potassium levels) were also observed in several brain regions. These data suggest that reduced Na/K-exchanging ATPase (EC 7.2.2.13) activity could contribute to the contrasting changes in sodium and potassium measured here.
血管性痴呆（VaD）是老年人认知障碍的第二大常见病因。然而，目前尚无已知的可改变疾病进程的VaD治疗方法，这可能是由于对该疾病分子基础的理解不完整所致。尽管神经退行性疾病的病因复杂，但越来越多的研究表明，金属稳态失衡可能参与了几种与年龄相关的痴呆症的发病机制。然而，相比之下，关于VaD患者脑内金属水平的研究仍然很少。为了阐明金属稳态失衡在VaD中的可能作用，我们采用电感耦合等离子体质谱法对来自七个脑区的10例VaD脑组织和10例年龄及性别匹配的对照脑组织中的必需金属水平进行了定量分析。我们发现了新的证据，在所分析的七个区域中的六个区域，VaD脑组织中的湿重脑钠水平升高。在几个脑区还观察到脑钾水平降低以及钠/钾比值升高（与高组织钠水平和低钾水平一致）。这些数据表明，钠/钾交换ATP酶（EC 7.2.2.13）活性降低可能导致了此处所测钠和钾的相反变化。
