| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
REPORT
1Departments of Biophysics and 2Psychobiology, Universidade Federal de São Paulo/Escola Paulista de Medicina, São Paulo, Brazil
Submitted 31 October 2007; accepted in final form 28 June 2007
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
). It has been shown that either enforced or voluntary moderate exercise is a helpful tool against brain disorders, such as depression and anxiety (Goodwin 2003; Petrovitch and White 2005), as it has beneficial effects on cognitive functions (Gomez-Pinilla et al. 2002). Indeed it has been reported that chronic voluntary exercise improves murine performance on the one-trail passive avoidance task (Samorajski et al. 1985), whereas long periods of voluntary exercise increases acquisition rate of spatial learning on an eight-arm radial maze (Anderson et al. 2000) and enforced moderate exercise improves spatial learning in a water maze (Ang et al. 2006). In addition, exercise can enhance neurogenesis (Pereira et al. 2007) and upregulate the expression of trophic factors, which are associated with enhanced memory and long-term potentiation (van Praag et al. 1999; Vaynman et al. 2003).
The same does not certainly stand for intense exercise (IE), which can be drastically injurious according to the subject's physical fitness (Peijie et al. 2003). In fact, this kind of exercise generates high levels of reactive oxygen species, leading to oxidative damage of important macromolecules (Aguiló et al. 2005). Although moderate exercise causes adaptation of brain antioxidant and repair systems by increasing its resistance to oxidative stress (Radák et al. 2001; Somani and Husain 1997), acute and IE seems to enhance its lipid peroxidation (Hara et al. 1997; Somani et al. 1996). However, the effects of IE on either oxidative damage or antioxidant status of the brain are still conflicting, and some authors did not observe exercise-induced alterations in the brain lipid peroxidation or in the antioxidant enzymes activities (Acikgoz et al. 2006; Özkaya et al. 2002).
Considering that it is quite easy to misjudge the appropriate intensity of the daily exercise session with the individual level of physical conditioning, it is essential to unravel the interference of IE on cognitive process as it may have important consequences on people skills and work skills. As observations in humans are difficult to interpret because they can be influenced by the subject's expectancy of exercise-induced either positive or negative effects (Hogervorst et al. 1996), we investigated the effects of IE on the memory of animals supplemented or not with vitamins E and C, to explore the possible relationship between exercise-induced brain oxidative damage and exercise-induced memory impairment.
|
METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
Inbred male C57BL/6 mice, 28 ± 2 g, were obtained from Centro de Desenvolvimento de Modelos Experimentais para Medicina e Biologia—Universidade Federal de São Paulo animal facility, housed five animals per cage with water and food ad libitum. Animals were kept on a 12:12-h light-dark cycle (06:00–18:00 h) and maintained at 23°C for 
5 days before any experimental procedure. Animals were divided in four groups: sedentary (control), submitted to IE for 10 days (Ex. 10D), supplemented sedentary (control-V), and supplemented exercised (Ex. 10D-V). Animal-handling procedures were approved by our University Ethics Committee in adherence to the International Guiding Principles for Biomedical Research Involving Animals. Independent animal groups, experimental and the corresponding control, were used for each cognitive test, except for shock sensitivity which was performed immediately after the elevated plus maze test.
Exercise protocol
Animals were submitted to treadmill (Exer 3/6 Treadmill, Columbus Instruments, Columbus, OH)-enforced running, a kind of exercise in which intensity and duration can be easily manipulated and quantified as opposed to voluntary wheel or swimming exercises (Cunliffe-Beamer and Les 1987). Animals from all groups were initially acclimated to treadmill environment by performing a daily running session at 10 m/min for 15 min during five successive days (adaptation period). After this period, the individual maximum velocity was determined by submitting each animal to an incremental test (IT 1), which consisted of 3-min warm-up at 5 m/min, then adjustment of the treadmill speed at 10 m/min, followed by steps of 1 min with progressive increases of 1 m/min until the animal reached exhaustion, terminating in a 3-min cool down at 5 m/min. The exercised animal groups started the training exercise program 24 h after the IT, and each daily session consisted of a single IE session during 10 consecutive days, according to the following schedule: 1) 3-min warm-up at 5 m/min; 2) running at 85% of the individual maximum velocity until animal reached exhaustion; and 3) 3-min cool down at 5 m/min. The treadmill grade was maintained at 0% throughout the adaptation period, the daily exercise training session, and in two ITs as well. Mice were motivated to run with gentle hand prodding. Electrical shock was avoided as a negative reinforcement because this would add undue stress to the animals not typically associated with exercise. Control animals were exposed to the same environment conditions (handling, treadmill motor noise, vibration, and deprivation of food and water), whereas the other animals performed their daily exercise session.
Training intensity markers
PHYSICAL PERFORMANCE. Physical performance was assessed by determining the maximum treadmill velocity reached by each animal in the incremental test. Each animal performed two ITs, the first, 24 h after the last day of the adaptation period (IT 1) and the second, either 36 h after the last day of exercise training session or 12 h before the performance of the cognitive tests (IT 2).
BLOOD LACTATE CONCENTRATION. Blood samples (25 µl) were collected from the caudal vein of the animals at rest, immediately after IT 1, and at the 10th day of training. Blood samples were stored in 50 µl 1% natrium fluoride and frozen at –20°C. Blood lactate concentration was measured in a lactate analyzer (YSI Model 1500 Sport Lactate Analyzer, YSI) according to the producer's technical specifications.
Supplementation
Supplemented animal groups were simultaneously supplemented with 10 mg/kg vitamin E and 10 mg/kg vitamin C (Faria et al. 2005), once a day and 2 h before the beginning of the exercise session. The vitamin supplementation was administered intraperitoneally, in volumes not exceeding 1 ml/kg body wt. The treatment started at the first day of the adaptation period and finished at the last exercise session, thus summing up a whole period of 16 days of vitamin supplementation. Control animals were daily and intraperitoneally injected with the same volume of saline solution.
Behavioral procedures
INHIBITORY AVOIDANCE TASK (IAT). Memory performance was assessed by the level of the animal performance in the inhibitory avoidance task done 24 h after the last exercise training session. The avoidance apparatus consisted of a white and a black (light and dark) compartment, separated by a sliding door, with a controlled shock generator connected to the floor, which consisted of a metal grid with the bars 1.0 cm apart from each other. The inhibitory avoidance task included two sessions: the acquisition training and the retention test. In the acquisition training, each animal was placed inside the white compartment of the avoidance apparatus for 10 s with the sliding door closed. Then the sliding door was opened, and as soon as the animal got into the black compartment with all four paws, the door was closed again and three foot shocks (0.5 mA/1 s at each 30 s) were delivered. The time interval elapsed between the opening of the sliding door and the moment the animal got into the black compartment with its four paws corresponds to the latency time. Fifteen seconds after the last foot shock, the animal was removed from the apparatus and kept in the homecage for 30 min before being submitted to the retention test. The procedure of the retention test was exactly the same as that described for the acquisition training but without the foot shock delivery, and the animal was removed as soon as it got into the black compartment (4 paws in). The latency time was recorded as described before, and the higher this value, the better the animal memory performance. A maximum latency time of 180 s was ascribed to the animals that did not get into the black compartment.
CONTEXTUAL FEAR CONDITIONING TASK (CFC) AND TONE FEAR CONDITIONING TASK (TFC).
The tasks were performed according to Ferreira et al. (2003) with some modifications. These two tasks also comprised two sessions, the acquisition training and the retention test. The acquisition training procedure was the same for both CFC and TFC tasks and was performed 24 h after the last exercise session. Each animal was confined in the black compartment of the avoidance apparatus with the sliding door closed for 3 min when a 60-dB tone was sounded for 5 s. In the last second of the tone, a foot shock (0.5 mA, and 1-s duration) was simultaneously delivered so that both stimuli, electrical and sound, ended at the same time. This procedure was repeated five times at 25-s intervals. Then, the animal was removed from the avoidance apparatus 30 s after the fifth foot shock and returned to its homecage, so that the whole acquisition procedure lasted 5.5 min. After 30 min of rest, the animal was exposed to the same training context to perform the CFC retention test; that is, it was placed again in the dark compartment of the avoidance apparatus, but this time no foot shock was delivered. The freezing time, defined as the period of time the animal remained fully motionless with no evident signs of vibrissa movements and sniffing, was continuously recorded minute by minute for 5.0 min by a skilled observer. The TFC retention test was performed 24 h after its respective acquisition training and 48 h after the last exercise session. Mice were placed in a new context (i.e., the white compartment) for 5.0 min with the sliding door closed. At the end of the third minute, the same tone, utilized in the acquisition training, was delivered five times at 25-s intervals, throughout the fourth and fifth minute of exposure to the avoidance apparatus. The freezing time was measured, minute by minute, before and after the tone.
Animal anxiety levels were assessed 24 h after the last exercise session by elevated plus maze (EPM) test. The plus maze apparatus consisted of a cross with two open arms (30 x 7 cm) and two closed arms (30 x 7 cm with a wall 14 cm high), both arms standing at 50 cm above the floor. The animal was placed in the central segment of the EPM apparatus facing one of the open arms. The number of entries into and the time spent either in the open or in the closed arms were recorded for 5 min. The percentage of entries into the open arms was calculated relative to the total entries in either open or closed arm. The apparatus was cleaned with alcohol after the end of each animal performance to avoid any smell interference between distinct animals. The total number of entries was used as a measure of locomotion.
Shock sensitivity test was performed, immediately after EPM test, by placing each animal in the dark compartment of the avoidance apparatus with the sliding door closed. Foot shocks of progressive intensity were delivered, starting at 0.1 mA, followed by increment steps of 0.1 mA at 30-s intervals until the animal either flinched (coordinated movements of paw withdrawal) or vocalized. The intensity of the shock necessary to produce one of these two behaviors was recorded.
Oxidative stress levels
LIPID PEROXIDATION ASSAY.
Peroxidative damage to membrane lipid constituents from whole brain was determined by measuring the chromogen reaction product of 2-thiobarbituric acid (TBA) with one of the products of membrane lipid peroxidation, malondialdehyde (MDA), according to the technique described by Winterbourn et al. (1985) and adapted by Rosa et al. (2005). In brief, homogenate tissue pools were incubated for 30 min with the reaction mixture at 95°C. The chromogen reaction product was extracted in n-butanol, and its concentration was determined spectrophotometrically (N-200, Hitashi, Tokyo, Japan) at 532 nm. Results are expressed as nanomoles per milliliter per gram dry tissue.
CARBONYL ASSAY.
Oxidative damage to whole brain proteins was spectrophotometrically determined by quantifying tissue carbonyl content according to the method described by Reznick and Packer (1994). Briefly, 10 mM 2,4-dinitrophenylhydrazine (DNPH), dissolved in 2.5 M HCl, was added to brain homogenate pools from each animal group to generate chromophoric dinitrophenylhydrazones. After the DNPH reaction time, proteins were precipitated in 20% (wt/vol) trichloroacetic acid (TCA), followed by successive washings with ethanol/ethyl acetate mixture (1:1) and centrifugation at 6000 g. The last pellet was dissolved in 6 M guanidine–HCl solution. The protein carbonyl content was assessed spectrophotometrically (N-200, Hitashi) at 370 nm, using the molar extinction coefficient of DNPH, 
= 22,000 M–1 cm–1. The total protein content was measured in comparison with a bovine serum albumin standard curve (0.25–2.0 mg/ml) at 280 nm.
Solutions
The following solutions were used for lipid peroxidation assays: phosphate buffer solution (in mM): 20 KH2PO4, 150 KCl, and 40 HEPES; the reaction mixture: 20 mM phosphate buffer, 11% acetic acid, 0.1% tungstophosphoric acid, 0.5% SDS, and 0.2% TBA. For carbonyl assays the homogenizing buffer solution was: 50 mM NaH2PO4, 0.1% digitonin, plus a cocktail of antiproteases (5 mg/ml leupeptin, 7 mg/ml pepstatin, and 5 mg/ml aprotonin), and 1 mM EDTA.
Chemicals
All chemicals were analytical grade. Salts, D-glucose, n-butanol, TBA, tungstophosphoric acid, SDS, ascorbic acid (vitamin C), and acetic acid were purchased from Merck (Darmstadt, Germany); EDTA, 2,4-dinitrophenylhydrazine, TCA, cocktail of antiproteases, digitonin, guanidine, and 
-tocopherol (vitamin E) were from Sigma (St. Louis, MO).
Statistical analysis
Data are presented as means ± SE with n representing the number of experiments. Statistical significance was analyzed by t-test of Student's or ANOVA, followed by Newman-Keuls's test. P < 0.05 were considered statistically significant.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
Animal adaptation to the exercise protocol was assessed through two well-known IE markers: the physical performance and the blood lactate concentration (Boudet et al. 2004; Marquezi et al. 2003). After 10 days of IE training, a reduction of 34% in the maximum velocity reached by the exercised animals in the IT2 as compared with IT1 was observed (Table 1). Consistent with the high-intensity training, great accumulation of lactate in the exercised animal blood throughout the IE period was detected, starting from 2 mM before the training initiation (control) 
5 mM after the IT1, and reaching values >6 mM after the 10th day of IE (Table 1).
|
Data from the acquisition training of IAT were analyzed considering two factors: supplementation (saline or vitamin) and exercise (control or exercised). Neither supplementation [F(1,29) = 0.13, P = 0.72] nor exercise [F(1,29) = 0.19, P = 0.66] caused any significant effects on the latency time, and no interaction between supplementation and exercise [F(1,29) = 1.55, P = 0.22] animal groups was detected by two-way ANOVA analysis.
Concerning the retention test from IAT, a significant effect of supplementation [F(1,29) = 4.28, P < 0.05] and exercise [F(1,29) = 4.31, P < 0.05] with a significant interaction between them [F(1,29) = 4.74, P < 0.01], were detected by two-way ANOVA analysis. Thus intense and exhaustive exercise caused a significant decrease of 41% in the latency time in the exercised group as compared with the control. This reduction was fully prevented by concurrent vitamin C and E supplementation (Fig. 1A).
|
Data from the acquisition training from CFC and TFC tests were analyzed considering three factors: first, supplementation (saline or vitamins), second, exercise (control or exercised), and third, time (minute). A significant effect of time (minute) [F(3,105) = 47.02, P < 0.001] was detected in the three-way ANOVA analysis done with measurements of freezing time (s) at 1-min intervals (data not shown), but no effect of either supplementation [F(1,35) = 1.43, P = 0.23] or exercise [F(1,35) = 0.15, P = 0.69; Fig. 1B]). In addition, no interaction between supplementation and exercise, minute and supplementation, minute and exercise, or even among the three factors [F(1,35) = 0.52, P = 0.47; F(3,105) = 0.38, P = 0.76; F(3,105) = 0.03, P = 0.99; F(3,105) = 0.568, P = 0.63, respectively] were detected. Post hoc analysis (Newman-Keuls, P < 0.05) to time effect detected that mice from all groups presented more freezing behavior during the first minute after tone and shock presentation, than in all other minutes (P < 0.01).
CFC retention test
A significant effect of supplementation [F(1,35) = 6.67, P < 0.05] and exercise [F(1,35) = 17.39, P < 0.001] were detected in the two-way ANOVA. In addition, significant interaction between supplementation and exercise [F(1,35) = 9.48, P < 0.01] was detected. Post hoc analysis considering the interaction between supplementation and exercise factors detected that Ex. 10D group displayed the lowest total freezing time (P < 0.001; Fig. 1B).
TFC retention test
Three-way ANOVA detected significant effect of time (minute) [F(4,140) = 109.93, P < 0.001] but no effect of both the supplementation [F(1,35) = 4.02, P = 0.06] and the exercise [F(1,35) = 1.74, P = 0.19] factors. Significant interaction between minute and supplementation [F(4,140) = 6.02, P < 0.001] and minute and exercise [F(4,140) = 3.41, P < 0.05] and among the three factors [F(4,140) = 6.39, P < 0.001] were detected, in contrast to the absence of any interaction between supplementation and exercise [F(1,35) = 2.39, P = 0.13].
A post hoc test considering the interaction among the three factors detected that no differences were observed among the groups before the tone presentation (minutes 1–3). In contrast, immediately after the tone presentation (minutes 4 and 5), the Ex. 10D displayed the lowest freezing time (P < 0.05). Throughout the test, the control, control-V and Ex. 10D-V animal groups displayed similar freezing behavior. Throughout the second and third minutes, there was a significant increase (P < 0.05) of the freezing time as compared with the first minute, then followed by a significant increase (P < 0.05) immediately after the tone, at the fourth and fifth minutes, when the freezing time reached its highest values. On the other hand, the tone presentation did not alter the animal behavior of animals from Ex. 10D group, as there were no significant differences in the freezing time immediately before or after the tone presentation.
Shock sensitivity
No significant difference between control and Ex. 10D groups (P = 0.52) was detected with the Student's t-test (Fig. 2A).
|
No differences were detected between the control and Ex. 10D groups concerning the time spent either in the open arms or in the closed arms (Fig. 2B); but for both animal groups, the percent of total permanence time was higher in the closed arms than in the open arms. Moreover, the total number of entries in the open and closed arms, an indicative of locomotion, did not differ between the control and Ex. 10D animal groups (Fig. 2C). Altogether, these results suggest that there were no differences caused by exercise on the anxiety level and locomotor activity of the animals.
Lipid peroxidation assay
Two-way ANOVA detected significant effect of exercise [F(1,12) = 26.81, P < 0.001], supplementation [F(1,12) = 3.34, P < 0.05] and a significant interaction between these two factors [F(1,12) = 3.00, P < 0.05]. Post hoc analysis shows a significant increase of 150% in brain lipid peroxidation level of the Ex. 10D group compared with control group. The vitamin supplementation partially prevented the lipid peroxidation damage since animals from Ex. 10D-V presented a significant decrease of the LP levels compared with those from Ex. 10D group but still remained 60% higher than the LP level from the control-V group (Fig. 3A).
|
Two-way ANOVA detected significant effect of exercise [F(1,12) = 32.08, P < 0.001] and supplementation [F(1,12) = 42.63, P < 0.001] but no significant interaction between the two factors [F(1,12) = 0.001, P = 0.97]. The Ex. 10D group presented a significant increase of 31% on the protein carbonyl content, whereas the Ex. 10D-V presented the same levels as those from the control group. Finally, the supplementation also reduced the levels of protein carbonyl content in the control animals, as the control-V presented a significant decrease of 6% on the protein oxidation compared with the control group (Fig. 3B).
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
). Oxidative stress was evaluated by both the membrane lipid peroxidation and the protein oxidation levels of the brain from C57Bl/6 mice engaged in enforced IE training. In all tests performed, there was a significant learning impairment associated with increased oxidative stress in the brain of exercised animals. Both effects were prevented by 16 successive days of concurrent vitamin C (ascorbic acid) and E (-tocopherol) supplementation of the animals. This is, to our knowledge, the first study to clearly report on relationship between exercise-induced cognitive prejudice and brain oxidative stress.
Our first concern was to characterize as intense the designed exercise protocol, and this was done by determining the effects of exercise protocol on two well-known intensity exercise markers, the blood lactate concentration and the animal physical performance. The blood lactate concentration was >5 mM just after the IT1 and at the end of the exercise program (Table 1). This reference value, according to Billat et al. (2005), indicates that the exercise protocol applied can be classified as intense. Moreover, the observed reduction of 30% of the maximum velocity reached by the animals in the incremental test performed 36 h after the end of the exercise program (IT 2; Table 1) corroborates the high intensity of the exercise program because successive sessions of IE impaired animal physical performance, mainly when the resting period between two sessions was not long enough to allow the complete recovery from the last exercise session (Budgett 1998).
The significant reduction of both the latency time (Fig. 1A) in the IAT, and the total freezing time (Fig. 1B) in the CFC in exercised animals as compared with control animals clearly show that IE impairs hippocampus-dependent memory. This is quite interesting considering that hippocampus is a region of the brain known to be very sensitive to oxidative stress (Jolitha et al. 2006; Parihar and Pandit 2003). Moreover, the negative influence of IE also on hippocampus-independent memory, as assessed by the significant reduction of the freezing time in the TFC task (Fig. 1C), enlarges the influence of this kind of exercise to other areas of the brain. It could be raised the possibility that other intrinsic parameters, such as sensitivity to electrical shock, elevated anxiety level, and locomotion disturbances, might be responsible for the observed impairment of the cognitive test performance. However, these were discarded since both the control and exercised animals did not differ regarding their sensitivity to shock intensity (Fig. 2A), the time of permanence of the animals on the open arm of the EPM (Fig. 2B) and in their locomotor activity (Fig. 2C).
The observation that IE greatly affected all memory tasks, together with its well-known potent stimulus for increased formation of reactive oxygen species (Davies et al. 1982) led us to think that the cognition reduction induced by exercise might be related to brain oxidative stress, mainly because it has been already reported a straight relationship between cognitive impairment and brain oxidative stress (Serrano and Klann 2004). In accordance with these authors, we now demonstrated that the level of oxidative stress in the brain was significantly augmented in exercised animals as compared with control because higher level of both membrane lipid peroxidation and protein oxidation were observed, as assessed by the enhancement of MDA concentration, and accumulation of carbonyl groups in the brain, respectively (Fig. 3, A and B). These results are also in agreement with those from Tsakiris et al. (2006), who reported that either short or prolonged enforced swimming exercise induces oxidative stress in the rat brain. In addition, the exercise-induced brain oxidative stress herein reported was sensitive to the improvement of the antioxidant defense mechanisms of the animals because 16 days of supplementation with both vitamin C and E partially protected the brain from membrane lipid peroxidation and avoided brain protein oxidation (Fig. 3). More interestingly, the vitamin treatment also prevented the decrease in the general memory capacity caused by IE as the latency time, the total freezing time, and the minute-by-minute freezing time in the exercised supplemented animals were similar to those obtained in the control animals, supplemented or not (Fig. 1). These results indicate that both the IE and the vitamin and E supplementation may not be specifically targeted to discrete brain regions, like hippocampus, but may represent more global events. We cannot discard the possibility that the protective effect exerted by vitamin C and E supplementation could be due to other actions beyond the antioxidant effects of both vitamins, such as inhibition of pro-inflammatory cytokine release (Fisher et al. 2004). However, the straight relationship observed between exercise-induced brain oxidative stress and the impairment of cognitive function, on one hand, and the significant recovery of cognitive function and the reduced level of brain oxidative stress in exercised, but supplemented animals, on the other hand, strongly argue in favor of the importance of the antioxidant features of the vitamins C and E. Finally, it should be stressed that according to Faria et al. (2005), the simultaneous treatment with both vitamin C and E was more efficient to attenuate reserpine-induced oral dyskinesia, which is known to be associated with brain oxidative stress, than supplementation with either one of these vitamins.
It might be argued that the impairment of memory in mice submitted to enforced exhaustive and IE could be somehow related to the stress associated with enforced training. In rat model, Diamond et al. (1992) reported that increased level of the hormone corticosterone, >210 ng/ml, prejudices the learning process, while others reported positive effects of enforced moderate exercise on animal cognitive performance (Ang et al. 2006), despite the corticosterone increased level, 
280 ng/ml, induced by this kind of exercise (Ebal et al. 2007). Although there were no data, as far as we know, concerning the relationship among corticosterone levels, learning process, and exercise in murine model, the conflicting evidences in the literature and the lack of effect of vitamin C and E supplementation on corticosterone secretion related by Armario et al. (1989) allow us to rule out this alternative as an explanation for our results.
In the unique study on animal model about the effect of IE on memory, Ogonovszky et al. (2005) showed the beneficial effects of this kind of exercise. However, this was observed in aged rats (20–28 mo old), an experimental condition greatly favoring oxidative stress of the organism (Harman 1956). According to Tomporowski (2003), the researchers who have examined the effects of IE on human cognitive processes have consistently failed to detect a clear relationship between the exhaustive exercise and the processes involved in perception, sensory, integration, or discrimination. In fact, Hogervorst et al. (1996) demonstrated a positive impact of IE on the subject cognitive performance, but it could be argued that their results could be caused by the expectancy of the subjects for a positive effect of exercise rather than on the intrinsic exercise effect. Whereas Grebot et al. (2003) demonstrated that IE could increase the difficulty of recall shooting performance, Fleury et al. (1981) could not detect any clear influence of IE on a letter-detection task.
Finally, although the clear demonstration of the harmful effects of IE on the cognitive function was done in rodent model, which obviously cannot be directly extended to humans, it raises the important question about its consequences to human brain because it is quite easy for people to exceed their individual lactate threshold while performing exercise leading to significant mismatch between exercise intensity and their physical conditioning.
|
GRANTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
|
ACKNOWLEDGMENTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
|
FOOTNOTES |
|---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Address for reprint requests and other correspondence: M.G.M. Oliveira, Dept. of Psychobiology, Universidade Federal de São Paulo/Escola Paulista de Medicina, Rua Napoleão de Barros, 925, 04024002 São Paulo, SP, Brazil (E-mail: mgabi{at}psicobio.epm.br)
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
Aguiló A, Tauler P, Fuentespina E, Tur JA, Córdova A, Pons A. Antioxidant response to oxidative stress induced by exhaustive exercise. Physiol Behav 84: 1–7, 2005.[CrossRef][Medline]
Anderson BJ, Rapp DN, Baek DH, McCloskey DP, Coburn-Litvak PS, Robinson JK. Exercise influences spatial learning in the radial arm maze. Physiol Behav 70: 425–429, 2000.[CrossRef][Medline]
Ang ET, Dawe GS, Wong PT, Moochhala S, Ng YK. Alterations in spatial learning and memory after forced exercise. Brain Res 1113: 186–193, 2006.[CrossRef][ISI][Medline]
Armario B, Borras M, Campmany L. Lack of effect of alpha-tocopherol and ascorbic acid on the response of some physiological variables to immobilization stress in rat. Rev Esp Fisiol 45: 277–280, 1989.[ISI][Medline]
Billat VL, Mouisel E, Roblot N, Melki J. Inter- and intrastrain variation in mouse critical running speed. J Appl Physiol 98: 1258–1263, 2005.
Boudet G, Albuisson E, Bedu M, Chamoux A. Heart rate running speed relationships-during exhaustive bouts in the laboratory. Can J Appl Physiol 29: 731–742, 2004.[ISI][Medline]
Budgett R. Fatigue and underperformance in athletes: the overtraining syndrome. Br J Sports Med 32: 107–110, 1998.
Cunliffe-Beamer TL, Les EP. The laboratory mouse. In: The UFAW Handbook on the Care and Management of Laboratory Animals, edited by Poole TB. Harlow, UK: Longman Scientific and Technical, 1987, p. 275–308.
Davies KJ, Quintanilha AT, Brooks GA, Packer L. Free radicals and tissue damage produced by exercise. Biochem Biophys Res Commun 107: 1198–1205, 1982.[CrossRef][ISI][Medline]
Diamond DM, Benett MC, Fleshner M, Rose GM. Inverted-U relationship between the level of peripheral corticosterone and the magnitude of the hippocampal primed burst potentiation. Hippocampus 2: 421–430, 1992.[CrossRef][ISI][Medline]
Ebal E, Cavalie H, Michaux, Lac G. Effect of a moderate exercise on the regulatory hormones of food intake in rats. Appetite In press.
Faria RR, Abilio VC, Grassl C, Chinen CC, Negrao LT, de Castro JP, Fukushiro DF, Rodrigues MS, Gomes PH, Registro S, de Carvalho Rde C, D'Almeida V, Silva RH, Ribeiro Rde A, Frussa-Filho R. Beneficial effects of vitamin C and vitamin E on reserpine-induced oral dyskinesia in rats: critical role of striatal catalase activity. Neuropharmacology 48: 993–1001, 2005.[CrossRef][ISI][Medline]
Ferreira TL, Moreira KM, Ikeda DC, Bueno OF, Oliveira MGM. Effects of dorsal striatum lesions in tone fear conditioning and contextual fear conditioning. Brain Res 987: 17–24, 2003.[CrossRef][ISI][Medline]
Fisher CP, Hiscock NJ, Penkowa M, Basu S, Vessby B, Kallner A, Sjöberg LB, Pedersen B. Supplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscle. J Physiol 558: 633–645, 2004.
Fleury M, Bard C, Jobin J, Carriere L. Influence of different types of physical fatigue on a visual detection task. Percept Mot Skills 53: 723–730, 1981.[ISI][Medline]
Fornari RV, Moreira KM, Oliveira MGM. Effects of the selective M1 muscarinic receptor antagonist dicyclomine on emotional memory. Learn Mem 7: 287–292, 2000.
Gomez-Pinilla F, Ying Z, Roy RR, Molteni R, Edgerton VR. Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J Neurophysiol 88: 2187–2195, 2002.
Goodwin RD. Association between physical activity and mental disorders among adults in the United States. Prev Med 36: 698–703, 2003.[CrossRef][ISI][Medline]
Grebot C, Groslambert A, Pernin JN, Burtheret A, Rouillon JD. Effects of exercise on perceptual estimation and short-term recall of shooting performance in a biathlon. Percept Mot Skills 97: 1107–1114, 2003.[ISI][Medline]
Hara M, Iigo M, Ohtani-Kaneko R, Nakamura N, Suzuki T, Reiter RJ, Hirata K. Administration of melatonin and related indoles prevents exercise-induced cellular oxidative changes in rats. Biol Signals 6: 90–100, 1997.[ISI][Medline]
Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol 2: 298–300, 1956.
Hogervorst E, Riedel W, Jeukendrup A, Jolles J. Cognitive performance after strenuous physical exercise. Percept Mot Skills 83: 479–488, 1996.[ISI][Medline]
Jolitha AB, Subramanyam MV, Asha Devi S. Modification by vitamin E and exercise of oxidative stress in regions of aging rat brain: studies on superoxide dismutase isoenzymes and protein oxidation status. Exp Gerontol 41: 753–763, 2006.[CrossRef][ISI][Medline]
Marquezi ML, Roschel HA, Dos Santa Costa A, Sawada LA, Lancha AHJr. Effect of aspartate and asparagine supplementation on fatigue determinants in intense exercise. Int J Sports Nutr Exerc Metab 13: 65–75, 2003.[ISI][Medline]
Ogonovszky H, Berkes I, Kumagai S, Kaneko T, Tahara S, Goto S, Radak Z. The effects of moderate-, strenuous- and over-training on oxidative stress markers, DNA repair, and memory, in rat brain. Neurochem Int 46: 635–640, 2005.[CrossRef][ISI][Medline]
Özkaya YG, Agar A, Yargicoglu P, Hacioglu G, Bilmen-Sarikcioglu S, Ozen I, Aliciguzel Y. The effect of exercise on brain antioxidant status of diabetic rats. Diabetes Metab 28: 377–384, 2002.[ISI][Medline]
Parihar MS, Pandit MK. Free radical induced increase in protein carbonyl is attenuated by low dose of adenosine in hippocampus and mid brain: implication in neurodegenerative disorders. Gen Physiol Biophys 22: 29–39, 2003.[ISI][Medline]
Peijie C, Hongwu L, Fengpeng X, Jie R, Jie Z. Heavy load exercise induced dysfunction of immunity and neuroendocrine responses in rats. Life Sci 72: 2255–2263, 2003.[CrossRef][ISI][Medline]
Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM, Sloan R, Gage FH, Brown TR, Small SA. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci USA 104: 5638–5643, 2007.
Petrovitch H, White L. Exercise and cognitive function. Lancet Neurol 4: 690–691, 2005.[CrossRef][ISI][Medline]
Radák Z, Taylor AW, Ohno H, Goto S. Adaptation to exercise-induced oxidative stress: from muscle to brain. Exerc Immunol Rev 7: 90–107, 2001.[ISI][Medline]
Reznick AZ, Packer L. Oxidayive damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 233: 357–363, 1994.[ISI][Medline]
Rosa EF, Silva AC, Ihara SS, Mora OA, Aboulafia J, Nouailhetas VLA. Habitual exercise program protects murine intestinal, skeletal, and cardiac muscles against aging. J Appl Physiol 99: 1569–1575, 2005.
Samorajski T, Delaney C, Durham L, Ordy JM, Johnson JA, Dunlap WP. Effect of exercise on longevity, body weight, locomotor performance, and passive-avoidance memory of C57Bl/6J mice. Neurobiol Aging 6: 17–24, 1985.[CrossRef][ISI][Medline]
Serrano F, Klann E. Reactive oxygen species and synaptic plasticity in the aging hippocampus. Ageing Res Rev 3: 431–443, 2004.[CrossRef][ISI][Medline]
Somani SM, Husain K, Diaz-Phillips L, Lanzotti DJ, Kareti KR, Trammell GL. Interaction of exercise and ethanol on antioxidant enzymes in brains regions of the rat. Alcohol 13: 603–610, 1996.[CrossRef][ISI][Medline]
Somani SM, Husain K. Interaction of exercise training and chronic ethanol ingestion on antioxidant system of rat brain regions. J Appl Toxicol 17: 329–336, 1997.[CrossRef][ISI][Medline]
Tomporowski PD. Effects of acute bouts of exercise on cognition. Acta Psycol 112: 297–324, 2003.[CrossRef]
Tsakiris T, Angelogianni P, Tesseromatis C, Tsakiris S, Tsopanakis C. Alterations in antioxidant status, protein concentration, acetylcholinesterase, Na+, K+-ATPase, and Mg2+-ATPase activities in rat brain after forced swimming. Int J Sports Med 27: 19–24, 2006.[CrossRef][ISI][Medline]
van Praag H, Christie BR, Sejnowski TJ, Gage FH. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci USA 96: 13427–13431, 1999.
Vaynman S, Ying Z, Gomez-Pinilla F. Interplay between brain-derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity. Neuroscience 122: 647–657, 2003.[CrossRef][ISI][Medline]
Warburton DE, Nicol CW, Bredin SS. Prescribing exercise as preventive therapy. CMAJ 174: 961–974, 2006.
Winterbourn CC, Gutteridge JMC, Halliwell B. Doxorubicin-dependent lipid peroxidation at low partial pressures of O2. Free Radic Biol Med 1: 43–49, 1985.[CrossRef]
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
, introduction of the tone.
