Effects of Voluntary Wheel-Running Types on Hippocampal Neurogenesis and Spatial Cognition in Middle-Aged Mice

Abstract

While increasing evidence demonstrated that voluntary wheel running promotes cognitive function, little is known on how different types of voluntary wheel running affect cognitive function in elderly populations. We investigated the effects of various voluntary wheel-running types on adult hippocampal neurogenesis and spatial cognition in middle-aged mice. Male C57BL6 and Thy1-green fluorescent protein (GFP) transgenic mice (13 months) were equally assigned to one of the following groups: (1) T1: no voluntary wheel running; (2) T2: intermittent voluntary wheel running; and (3) T3: continuous voluntary wheel running. The Thy1-GFP transgenic mice were used to specifically label granule cells, since Thy-1 is a promoter for neuronal expression. Behavioral evaluations suggested that intermittent voluntary wheel running improved Morris water maze performance in middle-aged mice. The number of BrdU-positive cells was significantly higher in both intermittent and continuous voluntary wheel running compared with no voluntary wheel running. However, only intermittent voluntary wheel running facilitated the newborn cells to differentiate into granule cells, while newborn cells tended to differentiate into astrocytes and repopulation of microglia was also enhanced in the continuous voluntary wheel-running group. These results indicated that intermittent voluntary exercise may be more beneficial for enhancing spatial memory. Effective improvement of hippocampal neurogenesis was also caused by intermittent voluntary wheel running in middle-aged mice.

Positive effects of running exercise on astrocytes in the medial prefrontal cortex in an animal model of depression

“…On the other hand, published evidence has suggested that CUS significantly decreases cell proliferation in the neocortex in adult rats, and chronic antidepressant administration reverses the decrease in cortical cell proliferation (Banasr et al., 2007). Continuous voluntary wheel running significantly increases the number of BrdU + cells in the hippocampus of middle‐aged mice, and these new cells tend to differentiate into astrocytes (Huang et al., 2018). Similarly, voluntary exercise could increase astrocyte proliferation in the mPFC of control rats (Mandyam et al., 2007).…”

Exercise for Brain Health: An Investigation into the Underlying Mechanisms Guided by Dose

“…Animal models enable the study of the microscopic changes in brain structure that support exercise-mediated cognitive benefits, such as the formation of new neurons (neurogenesis) and synapses (synaptogenesis) in the hippocampus. One of the strongest and earliest links between exercise and cognition was found on neurogenesis [75][76][77], which was 1 of the first hypotheses used to explain the neurobiological underpinnings of exercise-mediated cognitive performance benefits. However, when considering the generalizability of these microscopic findings to translational research in aging humans, it is pertinent to also consider how age might impact processes such as neurogenesis and synaptogenesis.…”

The Sedentary Lifestyle and Masticatory Dysfunction: Time to Review the Contribution to Age-Associated Cognitive Decline and Astrocyte Morphotypes in the Dentate Gyrus

“…It is well known that long-term voluntary running improves learning and memory, by enchancing the strength of neuronal connections, through synaptic plasticity in the hippocampus [ 78 , 79 ], and increasing neurogenesis [ 55 , 80 ]. Continuous voluntary wheel running exercise also contributes to astrogenesis and the repopulation of microglia [ 81 ]. The voluntary running-enhanced plasticity seems to be mediated by the Notch1 signaling pathway [ 82 ] and brain-specific angiogenesis inhibitor 1 (BAI1) [ 83 ].…”