Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid.
Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid.
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DOI：
10.1186/1742-2094-5-13
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发表时间：
2008-04-09
影响因子：
9.3
通讯作者：
Cotman CW
中科院分区：
文献类型：
--
作者：
Nichol KE;Poon WW;Parachikova AI;Cribbs DH;Glabe CG;Cotman CW
炎症与阿尔茨海默病（AD）和转基因AD模型中的Aβ病理相关。以前，已经证明慢性刺激免疫反应会诱导促炎细胞因子IL-1β和TNF-α，这有助于神经退行性变。然而，最近的证据表明，诱导适应性免疫反应可减少Aβ病理，并具有神经保护作用。低浓度IFN-γ通过引导小胶质细胞向抗原呈递细胞分化来调节适应性免疫反应。我们的目的是确定运动是否可以诱导年龄（17-19个月）Tg2576小鼠的免疫特征转变为减少a β病理的反应。TG （n = 29）和WT （n = 27）小鼠分为久坐组（SED）和运动组（RUN）。给RUN动物笼内跑轮3周。取组织，切除海马和皮质。定量资料采用2 × 2方差分析和学生t检验进行分析。久坐Tg2576 （TGSED）小鼠海马中IL-1β和TNF-α显著高于野生型（WTSED） （p = 0.04, p = 0.006）。免疫应答蛋白IFN-γ和MIP-1α在TGSED小鼠中低于WTSED小鼠（p = 0.03, p = 0.07）。三周后，IL-1β和TNF-α下降至与WT无明显差异的水平，同时，TGRUN中IFN-γ和MIP-1α升高。与TGSED相比，在TGRUN动物中观察到CD40和MHCII（抗原呈递标志物）增加，斑块和血管内及其周围的CD11c染色也增加。在TGRUN中观察到的额外血管反应性与另一种激活免疫途径一致，涉及血管周围巨噬细胞。可溶性Aβ40 （p = 0.01）和可溶性纤维Aβ (p = 0.01)显著降低。运动将免疫反应从先天转变为适应性反应或替代反应。这种免疫反应的转变与晚期病理状态中a β的减少相一致。
Inflammation is associated with Aβ pathology in Alzheimer's disease (AD) and transgenic AD models. Previously, it has been demonstrated that chronic stimulation of the immune response induces pro-inflammatory cytokines IL-1β and TNF-α which contribute to neurodegeneration. However, recent evidence has shown that inducing the adaptive immune response reduces Aβ pathology and is neuroprotective. Low concentrations of IFN-γ modulate the adaptive immune response by directing microglia to differentiate to antigen presenting cells. Our objective was to determine if exercise could induce a shift from the immune profile in aged (17–19 months) Tg2576 mice to a response that reduces Aβ pathology. TG (n = 29) and WT (n = 27) mice were divided into sedentary (SED) and exercised (RUN) groups. RUN animals were provided an in-cage running wheel for 3 weeks. Tissue was harvested and hippocampus and cortex dissected out. Quantitative data was analyzed using 2 × 2 ANOVA and student's t-tests. IL-1β and TNF-α were significantly greater in hippocampi from sedentary Tg2576 (TGSED) mice than in wildtype (WTSED) (p = 0.04, p = 0.006). Immune response proteins IFN-γ and MIP-1α are lower in TGSED mice than in WTSED (p = 0.03, p = 0.07). Following three weeks of voluntary wheel running, IL-1β and TNF-α decreased to levels indistinguishable from WT. Concurrently, IFN-γ and MIP-1α increased in TGRUN. Increased CD40 and MHCII, markers of antigen presentation, were observed in TGRUN animals compared to TGSED, as well as CD11c staining in and around plaques and vasculature. Additional vascular reactivity observed in TGRUN is consistent with an alternative activation immune pathway, involving perivascular macrophages. Significant decreases in soluble Aβ40 (p = 0.01) and soluble fibrillar Aβ (p = 0.01) were observed in the exercised transgenic animals. Exercise shifts the immune response from innate to an adaptive or alternative response. This shift in immune response coincides with a decrease in Aβ in advanced pathological states.
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影响因子：
5.3
作者：
Adlard, PA;Perreau, VM;Cotman, CW
通讯作者：
Cotman, CW
影响因子：
3.5
作者：
Algotsson, A.;Winblad, B.
通讯作者：
Winblad, B.
DOI：
10.1046/j.1365-2362.2002.00994.x
发表时间：
2002-05-01
影响因子：
5.5
作者：
Fiala, M;Liu, QN;Vinters, HV
通讯作者：
Vinters, HV
影响因子：
9.3
作者：
Colton CA;Mott RT;Sharpe H;Xu Q;Van Nostrand WE;Vitek MP
通讯作者：
Vitek MP
影响因子：
3.3
作者：
Dudal, S;Morissette, C;Gervais, F
通讯作者：
Gervais, F