Pathogenesis of peroxisomal deficiency disorders (Zellweger syndrome) may be mediated by misregulation of the GABAergic system via the diazepam binding inhibitor

BACKGROUND: Zellweger syndrome (ZS) is a fatal inherited disease caused by peroxisome biogenesis deficiency. Patients are characterized by multiple disturbances of lipid metabolism, profound hypotonia and neonatal seizures, and distinct craniofacial malformations. Median live expectancy of ZS patients is less than one year. While the molecular basis of peroxisome biogenesis and metabolism is known in considerable detail, it is unclear how peroxisome deficiency leads to the most severe neurological symptoms. Recent analysis of ZS mouse models has all but invalidated previous hypotheses. HYPOTHESIS: We suggest that a regulatory rather than a metabolic defect is responsible for the drastic impairment of brain function in ZS patients. TESTING THE HYPOTHESIS: Using microarray analysis we identify diazepam binding inhibitor/acyl-CoA binding protein (DBI) as a candidate protein that might be involved in the pathogenic mechanism of ZS. DBI has a dual role as a neuropeptide antagonist of GABA(A) receptor signaling in the brain and as a regulator of lipid metabolism. Repression of DBI in ZS patients could result in an overactivation of GABAergic signaling, thus eventually leading to the characteristic hypotonia and seizures. The most important argument for a misregulation of GABA(A) in ZS is, however, provided by the striking similarity between ZS and "benzodiazepine embryofetopathy", a malformation syndrome observed after the abuse of GABA(A) agonists during pregnancy. IMPLICATIONS OF THE HYPOTHESIS: We present a tentative mechanistic model of the effect of DBI misregulation on neuronal function that could explain some of the aspects of the pathology of Zellweger syndrome

Alpha absolute power: motor learning of practical pistol shooting Potência absoluta de alfa: aprendizagem motora do tiro prático de pistola

The present study aimed at investigating changes in behavior (shooting precision) and electrophysiological variables (absolute alpha power) during the motor learning of practical pistol shooting. The sample was composed of 23 healthy subjects, right-handed, male, between 18 and 20 years of age. The task consisted of four learning blocks. A One-way ANOVA with repeated measures and a post hoc analysis were employed to observe modifications on behavioral and electrophysiological measures (p<0.05). The results showed significative differences between blocks according to motor learning, and a significant improvement in shooting's accuracy from both blocks. It was observed a decrease in alpha power in all electrodes examined during task execution when compared with baseline and learning control blocks. The findings suggest that alpha power decreases as the function of the motor learning task when subjects are engaged in the motor execution.<br>O presente estudo teve por objetivo investigar alterações nas variáveis comportamentais (precisão do tiro) e eletrofisiológicas (potência absoluta de alfa) durante o aprendizado motor do tiro prático de pistola. A amostra constituiu-se de 20 sujeitos saudáveis, destros, sexo masculino, faixa etária entre 18 e 20 anos. A tarefa consistiu de quatro blocos de aprendizagem. A análise estatística das variáveis comportamentais e eletrofisiológicas foram realizadas por meio de uma ANOVA one-way e uma análise post hoc (p<0,05). Os resultados demonstraram diferenças significativas entre os blocos em função do aprendizado motor, bem como uma sensível melhora na precisão do tiro de ambos os blocos. Foi observada uma diminuição na potência de alfa em todos os eletrodos analisados durante a execução da tarefa, quando comparados aos blocos de linha de base e controle da aprendizagem. Os achados sugerem que a potência em alfa diminui devido o aprendizado motor quando sujeitos estão engajados na execução de uma tarefa motora complexa

Leg muscle recruitment during cycling is less developed in triathletes than cyclists despite matched cycling training loads

Studies of arm movements suggest that interference with motor learning occurs when multiple tasks are practiced in sequence or with short interim periods. However, interference with learning has only been studied during training periods of 1-7 days and it is not known if interference with learning continues during long-term multitask training. This study investigated muscle recruitment in highly trained triathletes, who swim, cycle and run sequentially during training and competition. Comparisons were made to highly trained and novice cyclists, i.e. between trained multidiscipline, trained single-discipline and novice single-discipline athletes, to investigate adaptations of muscle recruitment that occur in response to ongoing multitask, or multidiscipline, training. Electromyographic (EMG) activity of five leg muscles, tibialis anterior, tibialis posterior, peroneus longus, gastrocnemius lateralis and soleus muscles, was recorded during cycling using intramuscular fine-wire electrodes. Differences were found between trained triathletes and trained cyclists in recruitment of all muscles, and patterns of muscle recruitment in trained triathletes were similar to those recorded in novice cyclists. More specifically, triathletes and novice cyclists were characterised by greater sample variance (i.e. greater variation between athletes), greater variation in muscle recruitment patterns between pedal strokes for individual cyclists, more extensive and more variable muscle coactivation, and less modulation of muscle activity (i.e. greater EMG amplitude between primary EMG bursts). In addition, modulation of muscle activity decreased with increasing cadence (i.e. the amplitude and duration of muscle activity was greater at higher movement speeds) in both triathletes and novice cyclists but modulation of muscle activity was not influenced by cadence in trained cyclists. Our findings imply that control of muscle recruitment is less developed in triathletes than in cyclists matched for cycling training loads, which suggests that multidiscipline training may interfere with adaptation of the neuromuscular system to cycling training in triathletes