Dados do Trabalho

Título

AEROBIC TRAINING REDUCES MICROGLIAL ACTIVATION AND TNFalpha RELEASE IN THE HYPOTHAMALAMUS OF HYPERTENSIVE RATS

Introdução

Spontaneously hypertensive rats (SHR) exhibit autonomic imbalance and blood-brain barrier (BBB) dysfunction, a pathophysiological condition that can be corrected by exercise training (T). Although microglia (MG) are not part of the BBB structure, they modulate its function through the synthesis/release of cytokines. In hypertensive condition, MG are activated releasing pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα), which is able to break down different BBB constituents. Here we hypothesized that the benefit of exercise training to ameliorate BBB integrity in hypertensive rats could be due to reduced TNFα release by MG.

Objetivo

To evaluate whether MG activation and TNFα release in the hypothalamus of SHR can be affected by T. 

Método

Wistar and SHR male rats (CEUA ICB/USP #3407080618) aged 90 days were divided into 4 groups: sedentary (W-S n=6) and trained Wistar (W-T n=6), sedentary (SHR-S n=6) and trained SHR (SHR-T n=6). T rats were submitted to treadmill training (50%-60% of maximum capacity, 1 h/day, 5 days/week) or kept S for 4 weeks). At the end of protocols, the hypothalamus, brainstem and cortex were collected and processed for isolation of mononuclear cells, followed by flow cytometry analysis to evaluate MG and TNFα+ labeling. Data was analyzed by two-way ANOVA followed by Bonferroni’s post-test. 

Resultados

SHR-S vs. W-S exhibited elevated neuroinflammation degree and increased MG activation compared to normotensive subjects, (7.0±1.4% vs.0.65±0.39%, p<0.0001) and TNFα release (95.2±3.6% vs. 33.9±24.6%, p=0.0007). Increased performance gain was observed in both T groups. After training, SHR-T exhibited a reduction in hypothalamic MG activation attaining values similar to Wistar rats (CD45lowCD11b+, SHR-T: 0.55±0.26% vs. W-S:0.65±0.39% p=0.99; vs. W-T: 0.41±0.28% p=0.98; vs. SHR-S: 7.0±1.4% p<0.0001). TNFα release was reduced in hypothalamus of SHR-T (CD11b+TNFα+, SHR-T: 59.4±17.0% vs. W-S: 33.9±24.6% p=0.15; vs. W-T: 41.9±4.6% p=0.6; vs. SHR-S: 95.2±3.6% p<0.01). SHR-S vs. W-S also exhibited higher MG activation and TNFα release in brainstem, but 4 weeks of training was not enough to reduce this condition. No difference was observed in the cortex.

Conclusão

Exercise training of moderate intensity efficiently reduces MG activation and consequently TNFα release in the hypothalamus of hypertensive rats, which could be one of the causes affecting the integrity of the BBB in neurogenic hypertension.