Erratum in: Effects of Tummo Meditation and Niguma Yoga on Brain Activity.

High Activities of BACE1 in Brains with Mild Cognitive Impairment

Central Nervous System-directed AAV2/5-Mediated Gene Therapy Synergizes with Bone Marrow Transplantation in the Murine Model of Globoid-cell Leukodystrophy

Operationalizing compensation over time in neurodegenerative disease.

During embryogenesis, incubation temperature and the hormonal environment influence gonadal differentiation of some reptiles, including all crocodilians. Current evidence suggests that aromatase, the enzyme that converts androgens to estrogens, has a role in sexual differentiation of species that exhibit temperature-dependent sex determination (TSD). During the temperature-sensitive period (TSP) of sex determination, we compared aromatase activity in the brain and gonads of putative male and female alligator embryos to determine if aromatase activity in the embryonic brain could provide the hormonal environment necessary for ovarian development in a TSD species. In addition, we assessed the pattern of aromatase activity in the brain and gonads of embryos treated with estradiol-17beta (E(2)) and incubated at male-producing temperatures to compare enzyme activity in E(2) sex-reversed females to control males and females. This has particular significance regarding wildlife species living in areas contaminated with suspected environmental estrogens. Gonadal aromatase activity remained low during the early stages of the TSP in both sexes and increased late in the TSP only in females. Aromatase activity in the brain increased prior to gonadal differentiation in both sexes. These results suggest that aromatase activity in the brain is not directly responsible for mediating differentiation of the gonad. E(2) exposure at male-producing temperatures resulted in sex-reversed females that had intermediate gonad function and masculinized brain activity. This study indicates the need to examine multiple end points and to determine the persistence of developmental alterations in contaminant-exposed wildlife populations.

Spatial integration during the brain's cognitive activity prompts changes in energy used by different neuroglial populations. Nevertheless, the organisation of such integration in 3D ‐brain activity remains undescribed from a quantitative standpoint. In response, we applied a cross‐correlation between brain activity and integrative models, which yielded a deeper understanding of information integration in functional brain mapping. We analysed four datasets obtained via fundamentally different neuroimaging techniques (functional magnetic resonance imaging [fMRI] and positron emission tomography [PET]) and found that models of spatial integration with an increasing input to each step of integration were significantly more correlated with brain activity than models with a constant input to each step of integration. In addition, marking the voxels with the maximal correlation, we found exceptionally high intersubject consistency with the initial brain activity at the peaks. Our method demonstrated for the first time that the network of peaks of brain activity is organised strictly according to the models of spatial integration independent of neuroimaging techniques. The highest correlation with models integrating an increasing at each step input suggests that brain activity reflects a network of integrative processes where the results of integration in some neuroglial populations serve as an input to other neuroglial populations.

Brain and muscle activation patterns during postural control affect static postural control

Brain cystathionine synthase: Vitamin-B 6 requirement for its enzymic reaction and changes in enzymic activity during early development of rats

Brain neurotransmitter serotonin is involved in the regulation of many physiological functions and types of behavior. The key enzyme of serotonin synthesis in the brain is tryptophan hydroxylase-2 (TPH-2). An association of the C1473G polymorphism in gene tph2 causing the replacement of Pro447 by Arg447 in TPH-2 molecule with enzyme activity in the mouse brain of 10 inbred strains was found. Association of the polymorphism with the TPH-2 activity in the brain of F2 hybrids between strains C57BL/6 and CC57BR was shown. The results indicate that the C1473G polymorphism in gene tph2 is the main factor determining the genetic defined variability of enzyme activity in the mouse brain.

Sublethal adverse effects may result from exposure of aquatic organisms to insecticides at environmentally relevant concentrations. Fingerlings of the common carp (Cyprinus carpio, Linnaeus, 1758), grass carp (Ctenopharyngodon idella, Valenciennes, 1844), and bighead carp (Aristichthys nobilis, Richardson, 1845) were exposed to diafuran, an insecticide widely used during rice cultivation in Southern Brazil. The aim of this study was to verify the relationship between the lethal concentration (LC50) of diafuran and the acetylcholinesterase (AChE) activity in brain and muscle tissues of these species as a possible early biomarker of exposure to this insecticide. LC50 was determined for fish exposed to diafuran concentrations during 96 h (short term): common carp: control, 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 mg L-1; grass carp: control, 1.0, 2.0, 3.0 and 3.5 mg L-1 and, bighead carp: control, 0.5, 1.0, 1.5, 2.0, 3.0 and 4.0 mg L-1, as well as the determination of AChE at concentrations near LC50 for these species. LC50 values (nominal concentrations) were 1.81 mg L-1 for the common carp, 2.71 mg L-1 for the grass carp and, 2.37 mg L-1 for the bighead carp. All carps exposed to diafuran were lethargic (lower concentrations) or immobile. Diafuran inhibited the acetylcholinesterase activity in brain (~38%) and muscle (~50%) of all species. Muscle of bighead carp under control treatment showed higher specific AChE activity than brain (14.44 against 5.94 µmol min-1 g protein-1, respectively). Concentrations of diafuran used for rice cropping may affect Cyprinus carpio, Ctenopharyngodon idella and Aristichthys nobilis behaviors and the AChE activities in brain and muscle of these species may be an early biomarker of toxicity of this insecticide.

MAO activity in rat brain mitochondria with tyramine as substrate at 100% oxygen concentration was three times as much as that at 20%. When serotonin served as substrate, difference in activities between the two oxygen concentrations was not significant. Similar results were obtained when rat liver MAO was used as the enzyme source. At 100% oxygen concentration, pargyline showed the most potent inhibition of MAO activity in liver mitochondria with tyramine as substrate, but inhibitions caused by pheniprazine and harmaline were not remarkable. At 100% oxygen concentration, harmaline showed the most potent inhibition of MAO activity in the liver when serotonin served as substrate, while inhibitions of the MAO activity by pargyline and pheniprazine were weak. At 20% oxygen concentration, harmaline showed the most potent inhibition of MAO activity in the brain when serotonin was used as substrate. These inhibitions were studied using Lineweaver-Burk plots. Pargyline revealed a noncompetitive inhibition to MAO activity in liver and brain with tyramine and serotonin as substrate, harmaline a competitive inhibition to MAO activity in liver and brain with tyramine as substrate, while noncompetitive inhibition to MAO activity in liver and brain was evident when serotonin was used as the substrate.

Positron emission tomography (PET) is a functional neuroimaging method that maps brain activity non-invasively. Statistical methods play an essential part in understanding and analysing functional PET data. Several Bayesian approaches have been proposed for neuroimaging techniques that arrange information on the brain structure or activity function. In this paper, Bayesian analysis was used to detect functional brain activity in single- and multiple-subject PET data. Free PET dataset analyses for a single subject and five multiple subjects were conducted. A total of 72 functional PET images were processed, 12 for each one of the five multiple subjects and for the single subject. Several ways to design multiple-subject PET data were introduced in this work. Bayesian analysis was performed on the five multiple-subject and the single-subject PET data. A comparison was presented to determine which statistical matrix design is applicable for brain detection activity in PET data. The results of the design matrix and brain activity detection were presented for each selected design matrix. The Bayesian estimation of each case of the PET dataset for all the subjects was plotted. The brain activity was plotted as voxels on a transparent brain image in three orthogonal planes. The voxels were visualised using the maximum intensity projection method. Results showed that brain activity could not be detected easily in single-subject PET data. Finding the activity in multiple subjects depended on the design matrix used for PET data analysis.

Along with the study of brain activity evoked by external stimuli, an increased interest in the research of background, “noisy” brain activity is fast developing in current neuroscience. It is becoming apparent that this “resting-state” activity is a major factor determining other, more particular, responses to stimuli and hence it can be argued that background activity carries important information used by the nervous systems for adaptive behaviors. In this context, we investigated the generation of information in ongoing brain activity recorded with magnetoencephalography (MEG) in children with autism spectrum disorder (ASD) and non-autistic children. Using a stochastic dynamical model of brain dynamics, we were able to resolve not only the deterministic interactions between brain regions, i.e., the brain's functional connectivity, but also the stochastic inputs to the brain in the resting state; an important component of large-scale neural dynamics that no other method can resolve to date. We then computed the Kullback-Leibler (KLD) divergence, also known as information gain or relative entropy, between the stochastic inputs and the brain activity at different locations (outputs) in children with ASD compared to controls. The divergence between the input noise and the brain's ongoing activity extracted from our stochastic model was significantly higher in autistic relative to non-autistic children. This suggests that brains of subjects with autism create more information at rest. We propose that the excessive production of information in the absence of relevant sensory stimuli or attention to external cues underlies the cognitive differences between individuals with and without autism. We conclude that the information gain in the brain's resting state provides quantitative evidence for perhaps the most typical characteristic in autism: withdrawal into one's inner world.

Electroencephalography (EEG) allows for the evaluation of real time changes in brain (electrocortical) activity during exercise. A few studies have examined changes in electrocortical activity using stationary cycling, but the findings have been mixed. Some of these studies have found increases in brain activity following exercise, while others have found decreases in brain activity following exercise. Hence, it is of importance to identify post-exercise changes in brain activity. Sixteen healthy, untrained subjects (8 males; 8 females) participated in the study. All 16 participants performed a graded exercise test (GXT) to volitional exhaustion on an upright cycle ergometer. Continuous EEG recordings were sampled before (PRE) and immediately following (IP) the GXT. Regions of interest were primarily the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and left and right motor cortex (MC). In the DLPFC, a frontal asymmetry index was also identified. There was a statistically significant increase in theta power in the DLPFC, VLPFC, and left and right MC from PRE to IP (all p < 0.05). There was also a shift towards right hemisphere asymmetry at the IP time point in the DLPFC (p < 0.05). Finally, there was an increase in alpha power from PRE to IP in the right MC (p < 0.05). EEG could prove to be an important way to measure the effects of central fatigue on brain activity before and immediately following exercise.

Maple syrup urine disease (MSUD) is a metabolic disorder biochemically characterized by the accumulation of branched-chain amino acids (BCAA) and their branched-chain keto acids (BCKA) in blood and tissues. Neurological dysfunction is usually present in the patients, but the pathophysiology of brain damage is still obscure. Considering that brain energy metabolism is possibly altered in MSUD, the main objective of this study was to determine creatine kinase activity in the brain of rats subjected to acute and chronic administration of leucine. Chronic hyperleucinemia was induced by subcutaneous administrations of 4.8 micromol leucine/g body weight, twice a day, from the 6th to the 21st postnatal day. For acute hyperleucinemia, 21-day-old rats received three administrations of the amino acid at 3 h interval. Twelve hours after the chronic treatment or 1 h after the acute one, rats were killed and creatine kinase activity measured. The results indicated that acute or chronic administration of leucine altered creatine kinase activity in the brain of leucine-treated rats. Considering the crucial role creatine kinase plays in energy homeostasis in brain, if these effects also occur in the brain of MSUD patients, it is possible that alteration of this enzyme activity may contribute to the brain damage found in this disease.

Significant dephosphorylation of glucose 6-phosphate due to glucose-6-phosphatase activity in rat brain in vivo was recently reported (Huang, M., and Veech, R.L. (1982) J. Biol. Chem. 257, 11358-11363). The evidence was an apparent more rapid 3H than 14C loss from the glucose pool and faster [2-3H]glucose than [U-14C]glucose utilization following pulse labeling of the brain with [2-3H,U-14C]glucose. Radiochemical purity of the glucose and quantitative recovery of the labeled products of glucose metabolism isolated from the brain were obviously essential requirements of their study, but no evidence for purity and recovery was provided. When we repeated these experiments with the described isolation procedures, we replicated the results, but found that: 1) the precursor glucose pool contained detritiated, 14C-labeled contaminants arising from glucose metabolism, particularly 2-pyrrolidone-5-carboxylic acid derived from [14C]glutamine; 2) [14C]glucose metabolite were not quantitatively recovered; 3) the procedure used to isolate the glucose itself produced detritiated, 14C-labeled derivatives of [2-3H,U-14C]glucose. These deficiencies in the isolation procedures could fully account for the observations that were interpreted as evidence of significant glucose 6-phosphate dephosphorylation by glucose-6-phosphatase activity. When glucose was isolated by more rigorous procedures and its purity verified in the present studies, no evidence for such activity in rat brain was found.