White matter (WM) pathology is a clinically predictive feature of vascular cognitive impairment and dementia (VCID). Mice overexpressing transforming growth factor‐β1 (TGF) with an underlying cerebrovascular pathology when fed a high cholesterol diet (HCD) develop cognitive deficits (VCID mice) that we recently found could be prevented by physical exercise (EX). Here, we further investigated cognitive and WM pathology in VCID mice and examined the cellular substrates of the protective effects of moderate aerobic EX focusing on WM alterations. Six groups were studied: Wild‐type (WT) and TGF mice (n = 20–24/group) fed standard lab chow or a 2% HCD, with two HCD‐fed groups given concurrent access to running wheels. HCD had a significant negative effect in TGF mice that was prevented by EX on working and object recognition memory, the latter also altered in WT HCD mice. Whisker‐evoked increases in cerebral blood flow (CBF) were reduced in HCD‐fed mice, deficits that were countered by EX, and baseline WM CBF was similarly affected. VCID mice displayed WM functional deficits characterized by lower compound action potential amplitude not found in EX groups. Moreover, there was an increased number of collapsing capillaries, galectin‐3‐expressing microglial cells, as well as a reduced number of oligodendrocytes in the WM of VCID mice; all of which were prevented by EX. Our findings indicate that a compromised cerebral circulation precedes reduced WM vascularization, enhanced WM inflammation and impaired oligodendrogenesis that all likely account for the increased susceptibility to memory impairments in VCID mice, which can be prevented by EX.

中文翻译：

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体育锻炼对血管性认知障碍和痴呆小鼠模型中认知和神经胶质白质病理学的益处。

白质 (WM) 病理学是血管性认知障碍和痴呆 (VCID) 的临床预测特征。当喂食高胆固醇饮食 (HCD) 时，过度表达具有潜在脑血管病变的转化生长因子-β1 (TGF) 的小鼠会出现认知缺陷（VCID 小鼠），我们最近发现这种缺陷可以通过体育锻炼 (EX) 来预防。在这里，我们进一步研究了 VCID 小鼠的认知和 WM 病理，并检查了专注于 WM 改变的适度有氧 EX 保护作用的细胞基质。研究了六组：野生型 (WT) 和 TGF 小鼠 ( n= 20–24/组）喂食标准实验室饲料或 2% HCD，两个喂食 HCD 的组同时使用跑步轮。HCD 在 TGF 小鼠中具有显着的负面影响，EX 阻止了 EX 对工作和物体识别记忆的影响，后者在 WT HCD 小鼠中也发生了变化。在 HCD 喂养的小鼠中，胡须诱发的脑血流量 (CBF) 增加减少，EX 抵消了缺陷，基线 WM CBF 也受到了类似的影响。VCID 小鼠表现出 WM 功能缺陷，其特征是 EX 组中未发现的复合动作电位幅度较低。此外，在 VCID 小鼠的 WM 中，塌陷的毛细血管、表达半乳糖凝集素 3 的小胶质细胞数量增加，少突胶质细胞数量减少；所有这些都被EX阻止了。