Effects of exercise intensity on the reactive astrocyte polarization in the medial prefrontal cortex

Abstract

Purpose: Physical exercise contributes to neuroplasticity by promoting cognitive functions, such as learning and memory. The astrocytic phenotype is closely associated with synaptic plasticity. This study aimed to determine whether astrocyte polarization and synaptic alterations in the medial prefrontal cortex (mPFC) are affected differently by high- and moderate-intensity exercise.

Methods: Mice were subjected to moderate-(MIE) and high-intensity treadmill running (HIE). Memory capacity was assessed using the novel object recognition and modified Y-maze tests. For immunohistochemistry, c-Fos-positive cells were counted in the mPFC. Using western blot analysis, astrocyte phenotype markers were quantified in whole-cell lysates, and synaptic molecules were determined in the synaptosomal fraction.

Results: Exercise lengthened the approach time to novel objects regardless of intensity in the NOR test, whereas MIE only improved spatial memory. Exercise induced c-Fos expression in the anterior cingulate cortex (ACC) and c-Fos-positive cells were higher in MIE than in HIE in the ACC area. In the prelimbic/infralimbic cortex region, the number of c-Fos-positive cells were enhanced in MIE and decreased in HIE mice. The A1 astrocyte marker (C3) was increased in HIE mice, while the A2 astrocyte markers were enhanced in exercised mice, regardless of the intensity. In the synaptosomal fraction, synaptic proteins were elevated by exercise regardless of intensity.

Conclusion: These results suggest that exercise intensity affects neuronal plasticity by modulating the reactive state of astrocytes in the mPFC.

Keywords: astrocyte phenotype; exercise intensity; memory; neuronal activity; prefrontal cortex; synapse formation; treadmill running.

Figure 1.

The effects of exercise intensity on memory and neuronal activity in the mPFC. A. The experimental procedure. B–C. The quantitative analysis of exploration ratio in NOR test (B), and novel object entry and time (C). D. The photogram showing the area measured. E–F. Photomicrograph showing c-Fos-positive cells (E) and quantitative analysis (F). Data are presented as mean ± standard error. * and ** denote vs. CON p < 0.05 and p < 0.01, respectively. ^## vs. MIE p < 0.05 and p < 0.01, respectively.

Figure 2.

The effects of exercise intensity on astrocyte phenotype markers and synaptic proteins in the mPFC. A. Representative images of western blot for GFAP, C3, S100A10, PTX3, and GDNF. B. The quantitative analysis of GFAP, C3, S100A10, PTX3, and GDNF. C. Representative images of western blot for BDNF, synapsin-1, and PSD-95. D. The quantitative analysis of BDNF, synapsin-1, and PSD-95. Data are presented as mean ± standard error. * and ** denote vs. CON p < 0.05 and p < 0.01, respectively. ^## vs. MIE p < 0.05 and p < 0.01, respectively.