Raz Naftali, Daugherty Ana M, Bender Andrew R, Dahle Cheryl L, Land Susan
Department of Psychology and Institute of Gerontology, Wayne State University, 87 E. Ferry St., 226 Knapp Building, Detroit, MI, 48202, USA,
Brain Struct Funct. 2015 Sep;220(5):2663-74. doi: 10.1007/s00429-014-0817-6. Epub 2014 Jun 20.
The hippocampus is one of the most age-sensitive brain regions, yet the mechanisms of hippocampal shrinkage remain unclear. Recent studies suggest that hippocampal subfields are differentially vulnerable to aging and differentially sensitive to vascular risk. Promoters of inflammation are frequently proposed as major contributors to brain aging and vascular disease but their effects on hippocampal subfields are unknown. We examined the associations of hippocampal subfield volumes with age, a vascular risk factor (hypertension), and genetic polymorphisms associated with variation in pro-inflammatory cytokines levels (IL-1β C-511T and IL-6 C-174G) and risk for Alzheimer's disease (APOEε4) in healthy adult volunteers (N = 80; age = 22-82 years). Volumes of three hippocampal subfields, cornu ammonis (CA) 1-2, CA3-dentate gyrus, and the subiculum were manually measured on high-resolution magnetic resonance images. Advanced age was differentially associated with smaller volume of CA1-2, whereas carriers of the T allele of IL-1β C-511T polymorphism had smaller volume of all hippocampal subfields than CC homozygotes did. Neither of the other genetic variants, nor diagnosis of hypertension, was associated with any of the measured volumes. The results support the notion that volumes of age-sensitive brain regions may be affected by pro-inflammatory factors that may be targeted by therapeutic interventions.
海马体是对年龄最为敏感的脑区之一，然而海马体萎缩的机制仍不清楚。近期研究表明，海马体亚区对衰老的易损性不同，对血管风险的敏感性也不同。炎症促进因子常被认为是脑衰老和血管疾病的主要促成因素，但其对海马体亚区的影响尚不清楚。我们在健康成年志愿者（N = 80；年龄 = 22 - 82岁）中，研究了海马体亚区体积与年龄、一种血管风险因素（高血压）以及与促炎细胞因子水平变化（白细胞介素-1β C-511T和白细胞介素-6 C-174G）和阿尔茨海默病风险（载脂蛋白Eε4）相关的基因多态性之间的关联。在高分辨率磁共振图像上手动测量了三个海马体亚区的体积，即海马角（CA）1 - 2、CA3 - 齿状回和海马下脚。高龄与CA1 - 2体积较小存在差异关联，而白细胞介素-1β C-511T多态性的T等位基因携带者的所有海马体亚区体积均比CC纯合子小。其他基因变异以及高血压诊断均与任何测量体积无关。这些结果支持了这样一种观点，即对年龄敏感的脑区体积可能受到促炎因子的影响，而这些促炎因子可能是治疗干预的靶点。
