Avaliação de alterações metabólicas e comportamentais decorrentes de um episódio de restrição de tiamina através do método de modelagem autorregressiva.

Abstract

Thiamine is a B complex vitamin and its chronic restriction leads to severe clinical conditions such as beri-beri , Wernicke Encephalopathy and Wernecke-Korsakoff Syndrome. The use of experimental models of thiamine restriction is important in understanding the molecular, physiological and behavioral changes resulting from the deficiency of this vitamin. The objectives of this study were to evaluate the effects on behavioral, physiological and serotonergic parameters of adult Wistar rats on dietary restriction of thiamine. Thirty two rats were submitted or not to an episode of 7 weeks moderate restriction of thiamine, and were therefore divided according to the two treatment groups: deficient (DT, thiamine restricted diet, n = 16) and controls (C, standard diet, n=16), respectively. After this period, the standard diet was reestablished. All animals underwent a controlled manipulation (MC) three days before and three days after the episode of DT. After the 2nd MC all animals were exposed to the exploration of the open field (for 4 days). A week after the animals were sacrificed and samples of brain regions (thalamus-TAL, hippocampus-HIP, periaqueductal gray-PAG, and prefrontal cortex-CPF) were processed and analyzed via high-performance liquid chromatography for determining concentrations of serotonin (5-HT) and 5-hydroxy-indoleacetic acid (5-HIAA). ANOVA with repeated measures showed that the animals were DT after 49 days, on average 40 % lighter than the C (F(1,25)=39.973 ,p =0.001), eating 35% less water (F(1, 25)=7.116 ,p=0.037) and 70% less feed (F(1,25)=113.115, p<0.001). Comparing the behavioral dysplay before and after the deficiency was observed for the group DT a 36% increase in immobility (IMB, z=-3.41, p=0.0006), 33% reduction in ambulation (AMB, t=-3.36, p=0.0007), 12% in vertical exploration (EXP, t=-2.48, p=0.013) and 17% in resistance to capture (FIGHT, t=2.4, p=0.029). For group C these comparisons were not significant. The animals in the DT group traveled shorter distances during open field exploration in the four days, with significant on days 1 (t=2.601, p=0.014), 3(t=3.762, p=0.001) and 4 (t=2,641; p=0.013). There was no difference between groups with respect to [5-HT], but significant increase was observed in [5-HIAA] in the PAG of the DT group compared to C (t=-3.61, p=0.002). Analysis of correlation between [5-HT] and [5-HIAA] for each of the four brain regions in animals of Group C and TD showed the occurrence of an alteration induced by DT in standard association between these two variables only in HIP (r=0.54, p=0.03). It was observed an increased in the PAG of DT rats serotonergic activity (z=-3.36, p<0.001) and reduced in the CPF (t=3.76, p=0.002), evaluated from the renewal rate [5-HIAA]/[5-HT]. Significant correlations between serotonergic activity were also observed for group C(HIP-TAL: R=0.53, p=0.036; HIP-CPF: R=0.82, p=0.0001), but not for the group DT, where relationships were not significant. The greatest strength of correlations observed between renewal ratio and behaviors assessed on the 2nd MC were: DT group: IMB-TAL (R=-0.74, p=0.001) and AMB-TAL (R=0.71, p=0.002), group C: n/sig. DT group: HIP-FIGHT (R=0.74, p=0.001),. Group C:n/sig. The results show that the partial thiamine deficiency alters the pattern of activity of central serotonergic pathways and the animals’ coping style. We conclude that the neurochemical changes in response to the condition of moderate thiamine deficiency may lead to adjustments in the neural network. This adaptation of neuronal circuits to the state of DT can be modulated to meet hierarchically important for the survival of the individual, such as those related to behavioral responses to aversive stimuli demands. .