Review Article

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

Table 1

Description of included animal studies.

Author (year)AimAnimal species/experimental groupsBrain tissuesAnalysisProtocol of physical exercise

Gomes da Silva et al. [23]To investigate the morphological and functional hippocampal changes in adult rats submitted to daily treadmill exercise during the adolescent period.Male Wistar rats at 21 days of age were divided into two groups: exercise () and control ().HippocampusImmunofluorescence; ELISA; immunoblottingAn aerobic physical exercise protocol (running on a treadmill) was performed. Only animals that were classified as medium, above average, and good runner were included in the procedure. The physical exercise protocol was performed between days 21 and 60 of life. Each session started with a 5-minute warm-up at 8-10 m/minute. The running time and speed were gradually increased, reaching a maximum of 18 m/min for 60 min. Animals in the control group were treated in the same way as animals in the exercise group.

Aguiar et al. [24]Investigate whether long-term light physical exercise on a running wheel or treadmill improves spatial learning, memory, and plasticity of the hippocampus in elderly rats.Female Wistar rats aged 24 months were divided into two groups: exercised ( animals) and sedentary controls ( animals).HippocampusWestern blotting; RT-PCRAnimals underwent an adaptation period for 1 week on a treadmill, with a daily session of 3 minutes at a speed of 2 m/min. Then, the aerobic exercise protocol was started, which was performed for 4 consecutive weeks, with 4 sessions per week. Each exercise session consisted of a warm-up session (3 min, 2 m/min), followed by two sessions of running sessions (4-6 min) at a constant belt speed 10 m/min. Each session was spaced by a 1-minute rest interval.

Aguiar et al. [25]To analyze the effects of physical exercise on mitochondrial physiology, anxiodepressive-like behaviors and neuroplasticity in mice.Male C57BL/6 mice aged 8-10 weeks old were divided into two groups: voluntary exercise () and control group ().HippocampusRT-PCR; HPLC; Western blotting; spectrophotometrical assays for assessingA voluntary physical exercise protocol was carried out in individual cages equipped with a steering wheel to stimulate voluntary exercise for 6 weeks (Aguiar et al. [26]).

Bhattacharya et al. [27]To determine the effects of EGCG (∼250 mg/kg/day), B-ALA (∼550 mg/kg/day), and their combination with voluntary wheel running exercise.91 male BALB/cJ mice at 10 weeks of age were divided into eight groups: control ( sedentary and 11 runners), B-ALA ( sedentary and 12 runners), EGCG ( sedentary and 11 runners), or EGCG and B-ALA combined ( sedentary and runners).HippocampusImmunohistochemistryA voluntary physical exercise protocol was carried out for 39 days. Wheel rotations were monitored continuously in one-hour increments throughout the experiment via magnetic switches interfaced to the computer.

Brockett et al. [28]To investigate whether running alters performance on cognitive tasks that require the prefrontal cortex and whether any such changes are associated with astrocytic, as well as neuronal plasticity.Adult male Sprague-Dawley male rats are divided into two groups: sedentary controls () and runners () groups.Hippocampus; medial prefrontal cortex; orbitofrontal cortexImmunolabeling for astrocyte and synaptic markers; DiI impregnationA protocol of voluntary physical exercise in a running wheel was performed for 12 days. The running distance was recorded daily digital counters mounted on the racing wheels.

Kim et al. [29]To investigate the effect of treadmill exercise on impairment of cognitive function in relation with hippocampal neuroplasticity using high-fat diet-induced obese mice.C57BL/6 male mice at four weeks of age were divided into four groups: control group (), control and exercise group (), high-fat diet group (), and high-fat group and exercise ().HippocampusWestern blotting; immunohistochemistryAn aerobic exercise protocol was performed in treadmill for 20 weeks.

Vilela et al. [30]To investigate the effect of aerobic and strength training on spatial memory and hippocampal plasticity in aging rats.Male Wistar rats of 24 months old were divided into three groups: (/group) untrained, aerobic training, and strength training groups.HippocampusWestern blottingTwo physical exercise protocols were performed. The aerobic exercise protocol was performed on a running treadmill. Each session lasted 50 minutes and there was an interval of 48 hours between sessions. The anaerobic exercise protocol was performed through strength training. Climbing with 1 m inclined at 85° was carried out with weight attached to the tail. The weight attached to the tail was gradually increased from 50 to 100% during the 8 weeks of training. Three to five sets of 8 to 12 repetitions, with a 1-minute rest between repetitions and a 2-minute rest between sets, were performed for 3 or 4 days/week. Each session lasted 40 to 50 minutes, with an interval of 48 hours between sessions.

de Senna et al. [31]To investigate the effects of physical exercise to prevent or reverse spatial memory deficits produced by diabetes and some biochemical and immunohistochemical changes in hippocampal astrocytes of type 1 diabetes mellitus model.Three-month-old male Wistar rats were divided into four groups: nontrained control (), trained control (), nontrained diabetic (), and trained diabetic ().HippocampusImmunohistochemistry; morphological analysis of astrocytes.The aerobic physical exercise protocol was performed on a running treadmill at moderate intensity. The protocol took place once a day for 5x a week for 5 weeks.

Park and Kim [32]To assess the effects of paternal physical exercise on spatial learning ability in relation with hippocampal neuroplasticity in the rat pups born from the obese maternal rats.Male and female Sprague-Dawley rats of 4 weeks old were divided into four groups: nonexercising male and normal female group (), exercising male and normal female group (), nonexercise male and obese female group (), and exercise male and obese female group ().HippocampusImmunohistochemistry; Western blottingAn aerobic exercise protocol was performed on a running treadmill. The exercise was performed once a day and 6 days a week for 12 consecutive weeks [first 3 weeks (30 minutes—speed: 10 min/min); 4-6 weeks (40 minutes—10 m/min); 7-9 weeks (30 minutes—15 m/min); 10 to 12 weeks (40 min—15 m/min)].

Park et al. [33]To determine whether symptoms of chemo brain and disruptions in the neuroplasticity and functioning of hippocampal mitochondria can be prevented or relieved by exercise.Male Wistar rats of 6 weeks olds were divided into four groups: control (), control and exercise (), DOX-induced chemo brain (), and DOX-induced chemo brain and exercise ().HippocampusImmunofluorescence; immunohistochemistry; Western blottingAn aerobic exercise protocol was performed on a running treadmill. The exercise was performed once a day (30 min at 10 m/min) and six days per week for 4 consecutive weeks.

Park et al. [34]To investigate whether the decline in cognitive function caused by a high-fat diet could be improved through exercise by examining insulin signaling pathways and neuroplasticity in the hippocampus.Male C57BL/6 mice of 4 weeks old were divided into five groups: control (), control and exercise (), exercise (), high-fat diet (), and high-fat diet and exercise ().HippocampusImmunofluorescence; immunohistochemistry; Western blottingAn aerobic exercise protocol was performed on a running treadmill. The treadmill exercise started 20 weeks after taking the HFD. The exercise was performed once a day and six days per week for 12 consecutive weeks [1-2 weeks (30 min—10 m/min); 3-4 weeks (40 min—10 m/min); 5-6 weeks (30 min—13 m/min); 7-8 weeks (40 min—16 m/min); 9-10 weeks (40 min—16 m/min); 10-12 weeks (50 min—16 m/min)].

Yau et al. [35]Examine the effects of training on the administration of corticosterone on the hippocampus neurogenesis, cell proliferation and differentiation, synaptic protein expression, expression of neurotrophic factors, and behavioral analysis.Adult male Sprague-Dawley rats were divided into four groups (): (1) control rats (CON); (2) CORT- treated rats that could run only during the 2-week CORT administration period (CR); (3) CORT-treated rats with the 2 weeks prior running only (PR); and (4) CORT-treated rats that could run both prior and concurrently with the CORT administration period ().HippocampusImmunohistochemistry; Western blottingA protocol of voluntary physical exercise in a running wheel was performed for 34 days. The wheels were then unlocked for the rats with running for 14 days prior to the 50 mg/kg corticosterone treatment.

Pan et al. [36]To explore the specific role of physical exercise in novel object recognition memory after stroke and the exact cortical regions in which memory is restored by physical exercise.Spontaneously hypertensive rats of 10-12 weeks old were divided into four groups ( rats/group): control groups; tMCAO (2 d) group, in which rats underwent tMCAO surgery and NOR tests were performed 2 days later; the tMCAO (28 d) group, in which NOR tests were performed at 28 days post-tMCAO; and a tMCAO (28 d)+PE group, in which tMCAO was established and rats exercised in a running wheel for 26 consecutive days starting at the third day post-tMCAO.Entorhinal cortexHistochemistry; Western blottingThe physical exercise protocol was performed on a motorized racing wheel for 26 days from day 3 after treatment with tMCAO. During the first 12 days, the speed of 3 m/min was maintained for 20 minutes, twice a day. In the following 14 days, the speed was maintained at 6 m/min.

Rabelo et al. [37]To evaluate whether the intrinsic capacity for physical exercise influences dopamine neuroplasticity induced by physical training.Male Wistar rats of 2 months old were divided into three groups: low performance LP (), standard performance (SP) (), and high performance (HP) rats () which were randomized into the SED and TR groups.Not informedPCRThe aerobic exercise protocol was performed on a treadmill for 6 weeks, 5 times a week. The training time was obtained through an exercise test (40% of the maximum time obtained during the test of 60% ) and the speed was kept constant. The duration of the training sessions was increased by 10% per week (except for the transition from the 3rd to the 4th week).

Seo et al. [38]To evaluate whether exercise can improve psychiatric status and cognitive functioning, increasing the mitochondrial function of the hippocampus and neuroplasticity in a model of rats with posttraumatic stress disorder.Male Sprague-Dawley of 4 weeks old were divided into four groups: control (CON) group, a control and exercise (CON+EX) group, a PTSD group, and a PTSD and exercise (PTSD+EX) group ( in each group).HippocampusImmunofluorescence; Western blotting; mitochondrial analysisThe aerobic exercise protocol was performed on a treadmill once a day, 6 days a week, for 4 consecutive weeks. In the first two weeks, the exercise lasted 30 min with a speed of 10 m/min. In the third week, the rats performed 40 minutes of exercise at a rate of 12 m/min. In the fourth week, the exercise lasted 50 minutes at 13 m/min.

B-ALA: β-alanine; CORT: corticosterone; Dox: doxorubicin; ELISA: enzyme-linked immunosorbent assay; ECGC: epigallocatechin-3-gallate; EX: exercise; GFAP: glial fibrillary acidic protein; HPLC: high-performance liquid chromatography; NOR: novel object recognition; PE: physical exercise; PTSD: posttraumatic stress disorder; RT-PCR: real-time polymerase chain reaction; SED: sedentary; tMCAO: transient middle cerebral artery occlusion; TR: trained.