Exercise intensities modulate cognitive function in spontaneously hypertensive rats through oxidative mediated synaptic plasticity in hippocampus.

Oxidative damage in the brain may lead to cognitive impairments. There was considerable debate regarding the beneficial effects of physical exercise on cognitive functions because exercise protocols have varied widely across studies. We investigated whether different exercise intensities alter performance on cognitive tasks. The experiment was performed on spontaneously hypertensive rats (6 months at the established phase of hypertension) distributed into 3 groups: sedentary, low-intensity exercise and high-intensity exercise. Systolic blood pressure measurements confirmed hypertension in spontaneously hypertensive rats. In comparison to normotensive Wistar-Kyoto rats, sedentary spontaneously hypertensive rats had similar escape latencies and a similar preference for the correct quadrant in the probe trial. Compared to the sedentary group, the low-intensity exercise group had significantly better improvements in spatial memory assessed by Morris water maze. Low-intensity exercise was associated with attenuated reactive oxygen species, as measured by dihydroethidine fluorescence and nitrotyrosine staining in the dentate gyrus of the hippocampus. This was coupled with increased numbers of neurons and dendritic spines as well as a significant upregulation of synaptic density. In contrast, the beneficial effects of low-intensity exercise are abolished in high-intensity exercise as shown by increased free radical levels and an impairment in spatial memory. We concluded that exercise is an effective strategy to improve spatial memory in spontaneously hypertensive rats even at an established phase of hypertension. Low-intensity exercise exhibited better improvement on cognitive deficits than high-intensity exercise by attenuating free radical levels and improving downstream synaptic plasticity.

Differential effects of EPA and DHA on PPARγ-mediated sympathetic innervation in infarcted rat hearts by GPR120-dependent and -independent mechanisms.

The ω-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to attenuate inflammation processes, whereas the molecular mechanisms remain unclear. This study was aimed at figuring out the differential effects of EPA and DHA on fatal arrhythmias and whether the signaling pathway could be a target after myocardial infarction, an inflammatory status. Male Wistar rats after ligating coronary artery were randomized to either vehicle, EPA, or DHA for 4 weeks. Postinfarction was associated with increased myocardial norepinephrine levels and sympathetic innervation. Furthermore, infarction was associated with the activation of NLRP3 inflammasomes and increased the protein and expression of IL-1ß and nerve growth factor (NGF). These changes were blunted after adding either EPA or DHA with a greater extent of EPA than DHA. Immunoblotting and immunohistochemical analysis showed that EPA had significantly lower phosphorylation of PPARγ at Ser 112 compared with DHA. Arrhythmic severity during programmed stimulation in the infarcted rats treated with EPA was significantly lower than those treated with DHA. Specific inhibition of GPR120 by AH-7614 and PPARγ by T0070907 reduced the EPA-or DHA-related attenuation of IL-1ß and NGF release. Besides, AH-7614 treatment partially reduced the PPARγ levels, whereas T0070907 administration did not affect the GPR120 levels. These results suggest that EPA was more effective than DHA in prevention of fatal arrhythmias by inhibiting NLRP3 inflammasome and sympathetic innervation through activation of PPARγ-mediated GPR120-dependent and -independent signaling pathways in infarcted hearts.