Review Article

Effects of Physical Exercise on Neuroplasticity and Brain Function: A Systematic Review in Human and Animal Studies

Table 3

Description of the main results of animal studies.

Author (year)Neuroplasticity outcomesFunctional outcomes
Neurotrophins and receptorsCell signalingCell growth and differentiation

Gomes da Silva et al. [23]An increase in BDNF expression was observed in the hippocampus () and TrkB () in the exercise group when compared to the control group. There were no differences for P75NRT receptor ().No significant differences in neuronal density were found between the exercise group and control groups [CA1 (); CA3 (); DG ()]. However, the density of mossy fibers was higher in the hippocampal formation of the exercise group () when compared to the control group.Learning and memory of animals from exercise and control groups were analyzed in the water maze for five days. Latency () and length of the swimming path () in the exercise group were significantly shorter than in the control group. However, there were no differences in speed (), showing that the results were not influenced by physical conditioning. On day 66, the platform was removed from the water maze to assess the time spent in each of the four imaginary quadrants. The results showed that both groups showed preferences for the previous quadrant (). On day 96, the platform was replaced in the water maze to analyze long-term memory. It was observed that the latency in finding the platform was lower in the exercise group () compared to the control group.

Aguiar et al. [24]BDNF mRNA expression () and BDNF protein levels () were higher in the hippocampus of elderly rats after short light intensity exercises.Phosphorylation of Akt () and CREB () was greater in the hippocampus of trained elderly rats when compared to the control.Learning and memory were analyzed in the water maze. A reduction in the escape latency of the exercised group was observed when compared to the control group (). In addition, more time was spent in the correct quadrant () in the exercise vs. control group. There were no differences in swimming speed () and distance covered ().

Aguiar et al. [25]Physical exercise increased the expression of BDNF () and GDNF () in the hippocampus.Physical exercise increased the phosphorylation of the element responsive to cAMP and CREB protein in the hippocampus ().The effects of physical exercise on depression-like and anxiety-like behaviors were evaluated. In the elevated plus maze (EPM) test, it was observed that PE promoted an anxiolytic effect indicated by increased open arms by exercised rats compared to the control group [EPM open arms: % total arms entries (); time of investigation ()]. In the open field, there was an increase in the exploration of the central regions of the open field in exercised animals. The increase in locomotion () and exploration time in the center of the open field () was greater in the trained vs. sedentary group. In the tail suspension test, the exercised group showed reduced immobility (). However, no differences were found between groups regarding latency time ().

Bhattacharya et al. [27]Exercise increased the total number of BrdU+ cells in the granular layer of the dentate gyrus compared to the sedentary group ().To assess the conditioning of contextual fear, physical exercise increased the duration of freezing in the original context (). In the assessment of fear conditioning, physical exercise promoted a longer duration of freezing behavior ().

Brockett et al. [28]Runner animals showed an increase in PSD-95 in the hippocampus (), medial prefrontal cortex (), orbitofrontal cortex (), and perirenal cortex ().An increase in body area of astrocyte cells was observed in the hippocampus (), medial prefrontal cortex (), and orbitofrontal cortex () in the runners group when compared to the sedentary group. No differences were observed in the perirenal cortex. Concerning the density of the dendritic column, runner animals had an increase in the apical () and basal dendrites of the 2/3-layer pyramidal neurons () in the medial prefrontal cortex. There was also a significant increase in apical () and basal () trees in runner animals.Object memory testing was used to evaluate memory. Runners showed the highest discrimination ratio on the object in place task (). On the other hand, there was no difference in discrimination rates between groups on the novel object preference after 12 days of running (). To assess cognition, an attentional set-shifting task was performed. Runners showed an improvement in simple (), reversal (), and extradimensional () discrimination, changing the attention-changing task in terms of the number of attempts to reach the criterion. However, sedentary mice also performed the task as expected.

Kim et al. [29]Physical exercise increased the expression of BDNF and TrkB compared to the control and high-fat group ().Treadmill exercise increased the number of DCX-positive and BRDU-positive cells in control and high-fat diet-induced obese mice ().Memory was assessed by the Y-maze test. Treadmill exercise alleviated deterioration of spatial and short-term memory in control mice [spontaneous alternation (), correct number (), and error number ()] and obese patients induced by a high-fat diet.

Vilela et al. [30]Aerobic exercise showed an increase in PSD-95 levels when compared to the other groups (). However, the two physical exercise protocols showed improvements over the levels of pNMDA (), BNDF (), and p75NTR () when compared to the control. TrkB levels were decreased after aerobic exercise ().CREB increased after training for both exercise protocols ().The Barnes maze test was used to assess memory and cognition. The latency to find the escape orifice was reduced and spatial memory (increase in the time spent in the destination quadrant) was improved after the strength and aerobic exercise () compared to the sedentary group.

de Senna et al. [31]A significant increase in the number of astrocytic ramification in all directions was observed in trained diabetic rats when compared to the diabetic group ().Memory was assessed using the place recognition test. After physical training, the analysis of the exploration time of trained diabetic rats was greater than in the diabetic group ().

Park and Kim [32]Paternal exercise enhanced BDNF () and TrkB () expressions in the male rat pups from the obese maternal rats.Paternal exercise increased cell differentiation (DCX-positive cells; ) and cell proliferation (BrdU-positive cells; ) in the hippocampus of male rat pups from the obese maternal rats.Spatial learning ability was evaluated using the Morris water maze task. Paternal exercise reduced the escape latency () and time in probe quadrant (), improving the spatial learning capacity in male offspring of obese rats.

Park et al. [33]Physical exercise reduced the effects of CHEMO, increasing the levels of BDNF () and TrkB ().Exercise increased levels of cell proliferation in animals that received CHEMO [BRDU/Neun-positive cells in dentate gyrus ()].Short-term memory was assessed using the step-down avoidance task, and Morris water maze task was performed to assess spatial learning and working memory. A reduction in the step-down latency time (), escape latency (), and longer time in the quadrant probe () was observed in CHEMO+EX compared to the CHEMO group.

Park et al. [34]Exercise reduced the effects of the high-fat diet, increasing the hippocampal levels of BDNF () and TrkB ().Exercise reduced the effects of the high-fat diet, increasing cell proliferation [number of Brdu/NeuN-positive cells in the dentate gyrus ()] and cell differentiation [number of DCX-positive cells in the dentate gyrus ()].The Morris water maze test was used to assess spatial memory. Exercise reduced the effects of the high-fat diet, reduced escape latency (), stepped down latency time (), and increased time in probe quadrant ().

Yau et al. [35]Treadmill exercise improved levels of PSD-95 () and SYN () reduced by treatment with costicosterone.Treadmill exercise improved IGF-1 levels () reduced by treatment with costicosterone.Treadmill exercise improved levels of CIdU-positive cells (), number of proliferating cells in dentate gyrus (), CIdU-positive cells in the dentate gyrus (), IdU-labeled cells in dentate gyrys (), BrdU-positive cells () and increased neuronal differentiation (DCX cells, ) reduced by treatment with costicosterone.Depression-like behavior was measured according to the method of the forced swim test. Continuous running decreased immobility time () and decreased depression-like phenotypes compared to the CORT group.

Pan et al. [36]Physical exercise increased the reduced levels of SYN () and PSD-95 () in the entorhinal cortex in tMCAO rats.Physical exercise improved cell proliferation [nestin-positive cells (), Ki-67-positive cells (), and TUNEL-positive cells ()] in transient rats with middle cerebral artery occlusion (tMCAO).Memory was assessed by the novel object recognition test. Physical exercise improved memory (discrimination ratios, ) of the recognition of new objects in transient mice with occlusion of the middle cerebral artery (tMCAO).

Rabelo et al. [37]Physical training elicited an increase in Gdnf mRNA levels in the CPu of low performance rats (), whereas it decreased Bdnf expression only in high-performance rats ().

Seo et al. [38]There was an increase in hippocampal expression of BDNF () in animals trained with posttraumatic disorder. However, there was no difference in TrkB levels.There was no difference on positive cells for BrDU/NeuN and DCX in the dentate gyrus between the groups, with no differences on neurogenesis and cell differentiation.The open field, elevated plus maze, forced swimming test, and Morris water test were performed to assess depressive-like behavior, anxiety, depressive state, and spatial learning and working memory, respectively. The exercise group showed an increase in open arms () and time in open arms () when compared to the PTSD group. There was a reduction in immobility time () and average distance in the centers () in the PSTS+EX group. Thus, a reduction in anxiety, depression-like behavior, and a depressed state was observed in the trained animals. There was no effect of exercise on escape latency and time in the probe quadrant, and average distance from the center demonstrating no improvement in memory and learning.

AKT: protein kinase B; APE1: apurinic/apyrimidinic endonuclease 1; BNDF: brain-derived neurotrophic factor; CAMP: cyclic adenosine 3,5-monophosphate; CREB: cyclic amp-response element binding protein; CR: CORT-treated rats that were allowed to run only during 2 weeks; CORT: corticosterone; CPu: caudate-putamen; DAT: dopamine transporter; DOPAC: 3,4-dihydroxyphenylacetic acid; DA: dopamine; DCX: doublecortin; GDNF: glial cell-derived neurotrophic factor; HP: high performance; LP: low performance; mRNA: messenger RNA; PDS-95: postsynaptic density protein 95; p75NTR: p75 neurotrophin receptor; PR: CORT-treated rats of 2 weeks prior to running only; PE: physical exercise; TrkB: tropomyosin receptor kinase B; TR: trained; tMCAO: transient middle cerebral artery occlusion; 5-HT: serotonin.