Abstract
Running exercise, one of the strategies to protect brain function, has positive effects on neurons and synapses in the cortex and hippocampus. However, white matter, as an important structure of the brain, is often overlooked, and the effects of long-term running exercise on white matter are unknown. Here, 14-month-old male Sprague–Dawley (SD) rats were divided into a middle-aged control group (18-month-old control group), an old control group (28-month-old control group), and a long-term runner group (28-month-old runner group). The rats in the runner group underwent a 14-month running exercise regime. Spatial learning ability was tested using the Morris water maze, and white matter volume, myelinated fiber parameters, total mature oligodendrocyte number, and white matter capillary parameters were investigated using stereological methods. The levels of growth factors related to nerve growth and vascular growth in peripheral blood and the level of neurite outgrowth inhibitor-A (Nogo-A) in white matter were measured using an enzyme-linked immunosorbent assay (ELISA). The present results indicated that long-term running exercise effectively delayed the age-related decline in spatial learning ability and the atrophy of white matter by protecting against age-related changes in myelinated fibers and oligodendrocytes in the white matter. Moreover, long-term running exercise prevented age-related changes in capillaries within white matter, which might be related to the protective effects of long-term exercise on aged white matter.
Highlights
Using stereological methods, previous studies showed no significant loss of neocortical neurons with human aging (Pakkenberg and Gundersen, 1997; Pakkenberg et al, 2003)
We found a decrease in the number of mature oligodendrocytes with age, leading us to hypothesize that demyelination is the main cause of myelinated fiber loss in aged rat white matter (Li et al, 2009; Chen et al, 2011)
We investigated the levels of insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), FGF, and brainderived neurotrophic factor (BDNF) in the peripheral blood of aged rats but found no significant differences in the levels of IGF-1, VEGF, NGF, and FGF in the peripheral blood between the exercise group and the control group of the same age
Summary
Previous studies showed no significant loss of neocortical neurons with human aging (Pakkenberg and Gundersen, 1997; Pakkenberg et al, 2003). Stereological studies and imaging studies have found that white matter changes with normal aging (Tang et al, 1997; Guttmann et al, 1998; Jernigan et al, 2001). We found a decrease in the number of mature oligodendrocytes with age, leading us to hypothesize that demyelination is the main cause of myelinated fiber loss in aged rat white matter (Li et al, 2009; Chen et al, 2011). Besides in normal aging, Nasrabady et al (2018) found that the abnormalities of myelin and oligodendrocytes in the white matter were the important changes in Alzheimer’s disease (AD) pathology. White matter changes might be one of the key causes of brain function decline with normal aging
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