King's College London, Wolfson Centre for Age-Related Diseases, London, United Kingdom.
King's College London, Wolfson Centre for Age-Related Diseases, London, United Kingdom; Biochemistry Department, College of Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Am J Geriatr Psychiatry. 2015 Feb;23(2):141-8. doi: 10.1016/j.jagp.2014.05.001. Epub 2014 May 14.
Depression is a common symptom in dementia with Lewy bodies (DLB), Parkinson disease dementia (PDD), and Alzheimer disease (AD), yet its molecular basis remains unclear and current antidepressants do not appear to be effective. Cerebral zinc has been implicated in depression and synaptic dysfunction. We investigated the relationship between synaptic zinc regulation (for which zinc transporter 3 [ZnT3] is responsible) and depression in a large clinicopathologic study.
We examined brains from people with PDD (N = 29), DLB (N = 27), and AD (N = 15) and comparison subjects without depression or dementia (N = 24). Individuals were categorized according to the presence and severity of depression (on a scale of 0-3) based on standardized assessments during life (principally Neuropsychiatric Inventory). Western blotting was used to determine ZnT3 levels in Brodmann area 9 (BA9), and regression analysis was used to determine the relationship between ZnT3 and depression.
Reductions in ZnT3 in BA9 were significantly associated with elevated depression scores in the study cohort (β = -0.351, df = 93, t = -3.318 p = 0.0004). This association remained when only individuals with DLB, PDD, and no dementia or depression were examined (β = -0.347, df = 78, t = -3.271, p = 0.002) or only individuals with AD and no dementia or depression were examined (β = -0.433, df = 37, t = -2.924, p = 0.006).
Although decreased zinc levels have been implicated in the genesis of depression in animal models and in major depressive disorder in humans, this study provides the first evidence of a role for zinc in depression in people with dementia and highlights zinc metabolism as a therapeutic target.
抑郁是路易体痴呆（DLB）、帕金森病痴呆（PDD）和阿尔茨海默病（AD）的常见症状，但其分子基础仍不清楚，目前的抗抑郁药似乎无效。大脑中的锌已被牵涉到抑郁和突触功能障碍中。我们通过一项大型临床病理研究，研究了突触锌调节（锌转运蛋白 3 [ZnT3] 负责）与抑郁之间的关系。
我们检查了 29 例 PDD、27 例 DLB 和 15 例 AD 患者以及无抑郁或痴呆的对照患者（n=24）的大脑。根据生活中的标准评估（主要是神经精神疾病问卷），根据抑郁的存在和严重程度（0-3 分）对个体进行分类。使用 Western blot 确定 Brodmann 区 9（BA9）中的 ZnT3 水平，并使用回归分析确定 ZnT3 与抑郁之间的关系。
BA9 中的 ZnT3 减少与研究队列中抑郁评分升高显著相关（β=-0.351，df=93，t=-3.318，p=0.0004）。当仅检查 DLB、PDD 且无痴呆或抑郁的个体时，或仅检查 AD 且无痴呆或抑郁的个体时，这种关联仍然存在（β=-0.347，df=78，t=-3.271，p=0.002；β=-0.433，df=37，t=-2.924，p=0.006）。
尽管动物模型中的抑郁和人类重度抑郁症中锌水平的降低与抑郁的发生有关，但本研究首次提供了锌在痴呆患者抑郁中的作用的证据，并强调了锌代谢作为治疗靶点。
