Search

Abstract: Rett syndrome (RTT) is a rare X-linked autistic-spectrum neurological disorder associated with impaired energy metabolism, seizure susceptibility, progressive social behavioral regression, and motor impairment primarily in young girls. The objective of this study was to examine the influence of restricted diets, including a ketogenic diet (KD) and a standard rodent chow diet (SD), on behavior in male Mecp2 308/y mice, a model of RTT. The KD is a high-fat, low-carbohydrate diet that has anticonvulsant efficacy in children with intractable epilepsy and may be therapeutic in children with RTT. Following an 11-day pretrial period, adult wild-type and mutant Rett mice were separated into groups that were fed either an SD in unrestricted or restricted amounts or a ketogenic diet (KetoCal) in restricted amounts for a total of 30 days. The restricted diets were administered to reduce mouse body weight by 20–23% compared to the body weight of each mouse before the initiation of the diet. All mice were subjected to a battery of behavioral tests to determine the influence of the diet on the RTT phenotype. We found that performance in tests of motor behavior and anxiety was significantly worse in male RTT mice compared to wild-type mice and that restriction of either the KD or the SD improved motor behavior and reduced anxiety. We conclude that although both restricted diets increased the tendency of Rett mice to explore a novel environment, the beneficial effects of the KD were due more to calorie restriction than to the composition of the diet. Our findings suggest that calorically restricted diets could be effective in reducing the anxiety and in improving motor behavior in girls with RTT. [Copyright &y& Elsevier]

Abstract: The posterior cingulate cortex (PCC) is the brain region displaying the earliest sign of energy hypometabolism in patients with amnestic mild cognitive impairment (MCI) who develop Alzheimer’s disease (AD). In particular, the activity of the mitochondrial respiratory enzyme cytochrome oxidase (C.O.) is selectively inhibited within the PCC in AD. The present study is the first experimental analysis designed to model in animals the localized cortical C.O. inhibition found as the earliest metabolic sign of early-stage AD in human neuroimaging studies. Rats were used to model local inhibition of C.O. by direct injection of the C.O. inhibitor sodium azide into the PCC. Learning and memory were examined in a spatial holeboard task and brains were analyzed using quantitative histochemical, morphological and biochemical techniques. Behavioral results showed that sodium azide-treated rats were impaired in their memory of the baited pattern in probe trials as compared to their training scores before treatment, without non-specific behavioral differences. Brain analyses showed that C.O. inhibition was specific to the PCC, and sodium azide increased lipid peroxidation, gliosis and neuron loss, and lead to a network functional disconnection between the PCC and interconnected hippocampal regions. It was concluded that impaired memory by local C.O. inhibition in the PCC may serve to model in animals a metabolic lesion similar to that found in patients with amnestic MCI and early-stage AD. This model may be useful as an in vivo testing platform to investigate neuroprotective strategies to prevent or reduce the amnestic effects produced by posterior cingulate energy hypometabolism. [Copyright &y& Elsevier]

The large yellow croaker (Larimichthys crocea) is one of the most important marine economic fish in the southeast coast of China. However, hypoxia stress become a major obstacle to the benign development of L. crocea industry. To understand the energy metabolism mechanism adapted to hypoxia, we analyzed the transcriptome and physiology of L. crocea liver in response to hypoxia stress for different durations. We obtained 243,756,080 clean reads, of which 83.38% were successfully mapped to the reference genome of L. crocea. The heat map analysis showed that genes encoding enzymes involved in glycolysis/gluconeogenesis were significantly upregulated at various time points. Moreover, genes encoding enzymes related to the citrate cycle, oxidative phosphorylation, and amino acid metabolism were significantly downregulated at 6 and 24 h, but upregulated at 48 and 96 h. The change of liver in physiology processes, including respiratory metabolism, and activities of the carbohydrate metabolism enzymes showed a similar trend. The results revealed that the respiratory metabolism of L. crocea was mainly anaerobic within 24 h of hypoxia stress, and aerobic metabolism was dominant after 24 h. Carbohydrate metabolism plays a crucial role in energy supply and amino acid metabolism is an important supporting character to cope with acute hypoxia stress. There was no significant change in lipid utilization under short-term acute stress. This study increases our understanding of the energy metabolism mechanism of the hypoxia response in fish and provides a useful resource for L. crocea genetics and breeding. • The transcriptome of L. crocea liver was analyzed under hypoxia stress. • The adjustment of energy metabolism might be an effective strategy through which L. crocea responds to hypoxia stress. • Anaerobic metabolism and aerobic metabolism play an important role in the L. crocea 's response to hypoxia stress. • Glycometabolism plays a crucial role in hypoxia adaptation and amino acid metabolism is an important supporting character. [ABSTRACT FROM AUTHOR]