Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition - PubMed (original) (raw)

Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition

A Wu et al. Neuroscience. 2008.

Abstract

Omega-3 fatty acids (i.e. docosahexaenoic acid; DHA), similar to exercise, improve cognitive function, promote neuroplasticity, and protect against neurological lesion. In this study, we investigated a possible synergistic action between DHA dietary supplementation and voluntary exercise on modulating synaptic plasticity and cognition. Rats received DHA dietary supplementation (1.25% DHA) with or without voluntary exercise for 12 days. We found that the DHA-enriched diet significantly increased spatial learning ability, and these effects were enhanced by exercise. The DHA-enriched diet increased levels of pro-brain-derived neurotrophic factor (BDNF) and mature BDNF, whereas the additional application of exercise boosted the levels of both. Furthermore, the levels of the activated forms of CREB and synapsin I were incremented by the DHA-enriched diet with greater elevation by the concurrent application of exercise. While the DHA diet reduced hippocampal oxidized protein levels, a combination of a DHA diet and exercise resulted in a greater reduction rate. The levels of activated forms of hippocampal Akt and CaMKII were increased by the DHA-enriched diet, and with even greater elevation by a combination of diet and exercise. Akt and CaMKII signaling are crucial step by which BDNF exerts its action on synaptic plasticity and learning and memory. These results indicate that the DHA diet enhanced the effects of exercise on cognition and BDNF-related synaptic plasticity, a capacity that may be used to promote mental health and reduce risk of neurological disorders.

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Figures

Figure 1

Figure 1

DHA and exercise improve learning disability in rats. Learning performance was scored as average of escape latencies to locate the platform in the Morris water maze. The results demonstrated that DHA-enriched diet-fed rats perform better with lower escape latency (DHA-Sed) (21.4±3.4 s, 17.4.4±1.8 s, 13.6±2.0 s) than the rats-fed regular diet (RD-Sed) (34.6±4.5 s, 29.6±3.3 s, 21.7±2.5 s) while searching for the platform at days 3,4,5 of cognitive testing (A). Furthermore, exercise can boost the effect of DHA with much less latency (DHA-Exc) (16.3±4.0 s, 11.3±2.4 s, 8.8±1.0 s) to find the platform compared to DHA-enriched diet-fed rats (DHA-Sed) or exercised rats fed regular diets (19.0±2.4 s, 14.0±2.6 s, 11.8±2.0 s) at days 3,4,5 of cognitive testing (A). (B) The significant difference between these groups at day 5 was shown. *, P < 0.05; **, P < 0.01.

Figure 2

Figure 2

DHA and exercise affect pro-BDNF and mature BDNF levels in the hippocampus of rats. (A) DHA increased pro-BDNF, which was boosted by exercise. The values were converted to percent of RD-Sed group (mean ± SEM). *, P < 0.05. (B) DHA also increased mature BDNF, whereas exercise plus DHA led to greater elevation of mature BDNF. The mature BDNF and pro-BDNF in DHA-Exc rats were significantly higher than that in DHA-Sed rats. The values were converted to percent of RD-Sed group (mean ± SEM). *, P < 0.05.

Figure 3

Figure 3

DHA and exercise increase phosphorylated synapsin I and CREB response in the hippocampus. (A) Results show that DHA increased the ratio p-Syn I/t-Syn I, which was enhanced by exercise. This ratio in DHA-Exc rats was significantly higher than that in DHA-Sed rats. (B) Results show that DHA elevated p-CREB/t-CREB, which also was enhanced by exercise. The p-CREB/t-CREB ratio in DHA-Exc rats was significantly higher than that in DHA-Sed rats. The values were expressed as mean ± SEM. *, P < 0.05.

Figure 4

Figure 4

DHA and exercise increase phosphorylated Akt and CaMKII response in the hippocampus. (A) Results show that DHA elevated the ratio p-Akt/t-Akt, which was enhanced by exercise. (B) Results show that DHA elevated p-CaMKII/t-CaMKII, and this was enhanced by exercise. The values were expressed as mean ± SEM. *, P < 0.05. (C) There is a significant positive correlation between p-Akt and m-BDNF for all groups: RD-Sed, DHA-Sed, RD-Exc, and DHA-Exc (r = 0.82, p < 0.05).

Figure 5

Figure 5

Measurement of oxidized protein levels in rat hippocampus by western blot analysis of DNPH-derivatized carbonyl groups on oxidized proteins. DHA reduced oxidized protein levels, while exercise plus DHA led to greater reduction of oxidized protein levels (72%). The oxidized protein levels in DHA-Exc rats were significantly lower than that in DHA-Sed rats. The values were converted to percent of RD-Sed group (mean ± SEM). *, P < 0.05.

Figure 6

Figure 6

Possible mechanisms by which DHA dietary supplementation and exercise can affect synaptic plasticity and cognition. Both the DHA diet and exercise can increase the levels of BDNF acting on TrkB receptor signaling and resulting in the ctivation of synapsin I and CREB. A32.045ctivated synapsin I and CREB may contribute to enhance cognitive function. The Akt and CaMKII signaling systems can play a crucial intermediate role on the effects of DHA dietary supplementation and exercise on synaptic plasticity and cognitive function.

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