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It has been observed that, after 2 hours of aerobic exercise, plasma interleukin-6 (IL-6) increases whereas nuclear concentrations of enzyme DNA methyltransferase (DNMT) 3B significantly decreased in peripheral blood mononuclear cells (PBMCs), with no change observed in DNMT3A. The aim of the present study was to detect differences in these changes induced by exercise in plasma IL-6 levels as well as in PBMC nuclear concentrations of DNMT3A and DNMT3B, in relation to age and sex. Four groups were studied: 12 young men (24.8 ± 1.77 years old), 12 young women (23.8 ± 1.81 years old), 12 adult men (45.8 ± 1.82 years old), 12 adult women (mean 44.5 ± 2.07 years old). Participants had to run at 60% of maximal oxygen consumption (VO2max) for 120 minutes, interspersed with sprints at 90% of VO2max for the last 30 seconds of every 10 minutes. About 250 μL of PBMCs (1 × 10 cells) were treated with 100 μL of either pre-exercise plasma or post-exercise plasma and nuclear DNMT3A and DNMT3B concentrations were quantified. No change in nuclear concentration of DNMT3A following the exercise was observed. Conversely, nuclear concentrations of DNMT3B significantly decreased, with a reduction of about 78% in young men, 72% in young women, 61% in adult men, and 53% in adult women. Moreover, a strong positive correlation between the nuclear concentration of DNMT3B in PBMC following stimulation with post-exercise plasma and post-exercise plasma concentrations of IL-6 was observed in all the 4 studied groups. This study confirms that a single bout of endurance exercise is sufficient to decrease nuclear concentrations of DNMT3B and thus protein upregulation. Moreover, the epigenetic mechanisms induced by exercise apparently cause more intense changes in men than in women and that, in both of them, this effect seems to decrease with age.

The objective of this study was to verify, in a sample of university students, whether a relaxing technique called deep breathing (stress Intervention Functional IFA) is capable to improve the mood and to reduce the levels of stress. Thirty-eight adult healthy subjects (aged between 18 and 28 years) volunteered the study. They were randomly divided in two groups, the Experimental Group (N = 19) and the Control Group (N = 19). The subjects of the Experimental Group were submitted, once per week, to 10 treatment's sessions of Anti-stress Protocol, each lasting 90 min, whereas subjects of the Control Group sat ten times for 90 min, once per week, without practicing any treatment. The psychological state of mood and stress was evaluated using Measurement of Psychological Stress (MSP) and Profile of Mood State (POMS), while the biological profile of the stress was detected by measuring the heart rate and the salivary cortisol. The results obtained from the present research support the possibility that deep breathing technique is capable to induce an effective improvement in mood and stress both in terms of self-reported evaluations (MPS and POMS) and of objective parameters, such as heart rate and salivary cortisol levels. No statistically significant difference was found between men and women.

The neuropeptide PACAP modulates synaptic transmission in the hippocampus exerting multiple effects through different receptor subtypes: the underlying mechanisms have not yet been completely elucidated. The neurotransmitter acetylcholine (ACh) also exerts a well-documented modulation of hippocampal synaptic transmission and plasticity. Since PACAP was shown to stimulate ACh release in the hippocampus, we tested whether PACAP acting through ACh might indirectly modulate glutamate-mediated synaptic transmission at a pre- and/or at a post-synaptic level. Using patch clamp on rat hippocampal slices, we tested PACAP effects on stimulation-evoked AMPA receptor-mediated excitatory post-synaptic currents (EPSCs AMPA ) in the CA3-CA1 synapse and on spontaneous miniature EPSCs (mEPSCs) in CA1 pyramidal neurons. A subnanomolar dose of PACAP (0.5nM) decreased EPSCs AMPA amplitude, enhanced EPSC paired-pulse facilitation (PPF) and reduced mEPSC frequency, indicating a pre-synaptic decrease of glutamate release probability: these effects were abolished by simultaneous blockade of muscarinic and nicotinic ACh receptors, indicating the involvement of endogenous ACh. The effect of subnanomolar PACAP was abolished by a PAC1 receptor antagonist but not by a VPAC receptor blocker. At a higher concentration (10nM), PACAP inhibited EPSCs AMPA : this effect persisted in the presence of ACh receptor antagonists and did not involve any change in PPF or in mEPSC frequency, thus was not mediated by ACh and was exerted post- synaptically on CA1 pyramidal neurons. We suggest that a high-affinity PAC1 receptor pre-synaptically modulates hippocampal glutamatergic transmission acting through ACh. Therefore, administration of PACAP at very low doses might be envisaged in cognitive diseases with reduced cholinergic transmission., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objectives: To analyze the influences of blood lactate produced during a specific session of CrossFit® on intensity and selectivity of attention. The first was evaluated by measuring the reaction time and the second by analyzing divided attention with a dual task., Methods: Fifteen male professionals of CrossFit® volunteered in the study. The training session was the Workout Of the Day (WOD) called 15.5, marked as: 27-21-15-9 repetitions (without recovery) in term of calories measured by using a rowing ergometer (e.g. 27 rowed calories) and in term of barbell full squats (raising a weight of 43 kg for men and of 29.5 kg for women). Blood lactate, blood glucose, reaction time, execution time of a dual task, number of errors and number of omissions were measured at rest, at the conclusion of the session and 15 minutes after its end., Results: The levels of the blood lactate before the start of the session were considerably higher than those which normally occur at rest (<2 mmol /L), with a mean value of 4.5 mmol /l (± 1.99 SD). At the end of the workout session the blood lactate exhibited a significant increase, reaching a mean value of 13.8 mmol /l (± 1.18 SD) and then returning to values similar to the initial ones after 15 minutes. Blood glucose did not exhibit any statistically significant differences during the session. Reaction time, execution time, number of errors and number of omissions exhibited a significant worsening concomitantly with the increase in blood lactate., Conclusion: Athletes practicing CrossFit®, with high levels of blood lactate even at rest, should consequently have attentional performances somewhat limited.

We report on an 18-month-old boy with unilateral left eye blinking as a single ictal manifestation without facial twitching. The clinical onset of this phenomenon was first recorded (as an occasional event) at age 3 months, and it was overlooked. By age 6 months, the child's blinking increased to almost daily occurrence in clusters: during blinking the infant showed intact awareness and occasional jerks in the upper limbs and right leg. A video-electroencephalography (video-EEG) documented clinical correlation with a focal pattern arising from the left occipital region, and brain magnetic resonance imaging (MRI) revealed severe brain damage, consisting in poroencephalic hollows and increased spaces in the convexities involving a large area of the left cerebral hemisphere. The boy was prescribed sodium valproate (30 mg/kg/d), resulting in drastic reduction of his clinical seizures. Follow-up to his current age documented good general status, with persistent partial right hemilateral seizures. The blinking progressively disappeared, and is no longer recorded. The pathogenic hypotheses of the unilateral ictal blinking include involvement of the ipsilateral cerebral hemisphere and/or the cerebellar pathways. Review of previous reports of unilateral eye blinking, arising from the ictal ipsilateral brain, revealed that different damaged regions may give rise to blinking ictal phenomena, likely via the trigeminal fibres innervating the subdural intracranial structures and the pial vessels in the ipsilateral affected brain. The eye blinking in the present child represents a further example of an ictal phenomenon, which is predictive of the damaged brain region., (© EEG and Clinical Neuroscience Society (ECNS) 2014.)

We examined, on 28 healthy adult subjects, the possible correlations of an exhaustive exercise, and the consequent high blood lactate levels, on immediate (explicit) and delayed (implicit) motor execution of sequential finger movements (cognitive task). Moreover, we determined with transcranial magnetic stimulation whether changes in motor performance are associated with variations in excitability of primary motor area (M1) and supplementary motor area (SMA). We observed that, after an acute exhaustive exercise, the large increase of blood lactate is associated with a significant worsening of both explicit and implicit sequential visuomotor task paradigms, without gender differences. We also found that, at the end of the exhaustive exercise, there is a change of excitability in both M1 and SMA. In particular, the excitability of M1 was increased whereas that of SMA decreased and, also in this case, without gender differences. These results support the idea that an increase of blood lactate after an exhaustive exercise appears to have a protective effect at level of primary cortical areas (as M1), although at the expense of efficiency of adjacent cortical regions (as SMA).

The aim of this research was to assess the impact of a well-characterized extract from Citrus bergamia juice on adipogenesis and/or lipolysis using mesenchymal stem cells from human adipose tissue as a cell model. To evaluate the effects on adipogenesis, some cell cultures were treated with adipogenic medium plus 10 or 100 μg/mL of extract. To determine the properties on lipolysis, additional mesenchymal stem cells were cultured with adipogenic medium for 14 days and after this time added with Citrus bergamia for further 14 days. To verify adipogenic differentiation, oil red O staining at 7, 14, 21, and 28 days was performed. Moreover, the expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), adipocytes fatty acid-binding protein (A-FABP), adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), monoglyceride lipase (MGL), 5'-adenosine monophosphate-activated protein kinase (AMPK)α1/2, and pAMPKα1/2 was evaluated by Western blot analysis and the release of glycerol by colorimetric assay. Citrus bergamia extract suppressed the accumulation of intracellular lipids in mesenchymal stem cells during adipogenic differentiation and promoted lipolysis by repressing the expression of adipogenic genes and activating lipolytic genes. Citrus bergamia extract could be a useful natural product for improving adipose mobilization in obesity-related disorders.

The accumulation of lactate in the blood after a high-intensity exercise is associated with an increase of lactate extractions by the brain. Previously, a negative influence of blood lactate on attentional processes has been observed. The present study was carried out to examine the association of high blood lactate levels, induced with a maximal cycling, with another cognitive domain: working memory. For evaluation of working memory two different protocols were used: the first (Self-Ordered Pointing Task) capable of analyzing non-spatial working memory requiring the ability to generate and monitor a sequence of responses and the second for evaluating motor working memory necessary to perform a motor task. The study was carried out in 30 students (15 males and 15 females) who performed exhaustive exercise. In each subject, blood lactate was measured and motor as well as non-motor forms of working memory were evaluated before the exercise, at its end as well as 15 min after the exhaustion. It was observed that an increase of blood lactate levels is associated with a worsening of both types of working memory.

We compared, in 20 subjects, the effects of high blood lactate levels on amplitude and latency of P1, N1, P2 and N2 components of lower limb somatosensory evoked potential (SEP), an useful, noninvasive tool for assessing the transmission of the afferent volley from periphery up to the cortex. SEPs were recorded from CPz located over the somatosensory vertex and referenced to FPz with a clavicle ground. Measurements were carried out before, at the end as well as 10 and 20 min after the conclusion of a maximal exercise carried out on a mechanically braked cycloergometer. After the exercise, P2-N2 amplitudes as well as latency of P1 and N1 components showed small but significant reductions. On the contrary, latency of N2 component exhibited a significant increase after the exercise's conclusion. These results suggest that blood lactate appears to have a protective effect against fatigue, at least at level of primary somatosensory cortex, although at the expense of efficiency of adjacent areas.

Until the end of 18th century, the role of the cerebellum remained obscure. The turning point occurred when Luigi Galvani showed that muscle contraction is due to electricity and Alessandro Volta produced the battery, an apparatus based on the pairing of silver and zinc plates separated by brine soaked paper disks, capable to generate electricity. Luigi Rolando, at beginning of 19th century, was impressed by these two observations. He thought that, since the brain generates the movement, it must contain a device generating electricity. As a battery, it should be formed by overlapping disks and the cerebellum for Rolando seemed to be the right structure for such a characteristic laminar organization. He argued that, if the cerebellum is the battery that produces electricity for muscle activity, its removal would produce paralysis. Consequently, Rolando removed the cerebellum in a young goat and observed that the animal, before dying, could no longer stand up. He concluded that the cerebellum is a motor structure as it generates the electricity which produces the movement. The conclusions of Rolando were criticized by Marie-Jean-Pierre Flourens who observed that animals undergoing cerebellectomy were still able to move, even if with problems of balance. Flourens concluded that the role of the cerebellum "is to put in order or to coordinate movements wanted by certain parts of the nervous system, excited by others". It was necessary to wait up to 1891 when Luigi Luciani, observing a dog survived the cerebellectomy, described a triad of symptoms (asthenia, atony and astasis), unquestionably of cerebellar origin.

In our recent study was shown a significant recovery of damaged skeletal muscle of mice with X-linked muscular dystrophy (mdx) following low-intensity endurance exercise, probably by reducing the degeneration of dystrophic muscle. Consequently, in the present work, we aimed to identify proteins involved in the observed reduction in degenerating fibres. To this end, we used proteomic analysis to evaluate changes in the protein profile of quadriceps dystrophic muscles of exercised compared with sedentary mdx mice. Four protein spots were found to be significantly changed and were identified as three isoforms of carbonic anhydrase 3 (CA3) and superoxide dismutase [Cu-Zn] (SODC). Protein levels of CA3 isoforms were significantly up-regulated in quadriceps of sedentary mdx mice and were completely restored to wild-type (WT) mice values, both sedentary and exercised, in quadriceps of exercised mdx mice. Protein levels of SODC were down-regulated in quadriceps of sedentary mdx mice and were significantly restored to WT mice values, both sedentary and exercised, in quadriceps of exercised mdx mice. Western blot data were in agreement with those obtained using proteomic analysis and revealed the presence of one more CA3 isoform that was significantly changed. Based on data found in the present study, it seems that low-intensity endurance exercise may in part contribute to reduce cell degeneration process in mdx muscles, by counteracting oxidative stress., (© 2015 Authors.)

We studied, in healthy adult subjects, the association of high blood lactate levels, induced with an exhaustive exercise (12 subjects) or an intravenous infusion (four subjects) of a lactate solution (3 mg/kg in 1 min), with amplitude and latency of visual-evoked potentials. Amplitude of N75, P100, and N145 components did not show significant changes, whereas latency of P100 was reduced at exercise's end and that of N145 increased 10 min after the conclusion. Therefore, an increase of blood lactate induced by an exhaustive exercise or an intravenous infusion appears to induce an improvement in the conduction time between eye and striate cortex, while it seems to evoke a worsening of intracortical communication between striate and extrastriate areas.

The aim of this study was to determine if heightened stress had an adverse affect on the postural control of 14 young right‑handed females during quiet standing in either the presence or the absence of visual input. The level of stress was evaluated by measuring the free cortisol response to awakening (cortisol awakening response; CAR) and by employing the perceived stress scale (PSS). Overall mood disturbance was measured using the profile of mood states (POMS). Postural control was evaluated using a force platform by measuring the 95% confidence ellipse area described by the center of pressure during 5 balance positions maintained for at least 52 sec, each with open and closed eyes. The results of this study revealed a significant positive correlation between CAR, PSS and POMS for each of the studied subjects. Furthermore, it was observed that whilst the level of stress was capable of influencing postural stability, this influence was particularly evident when no visual information was available. Additionally, it was determined that maintenance of posture is easier when the dominant foot is ahead, regardless of visual input.

The Supplementary Eye Field (SEF) and the Frontal Eye Field (FEF) have been described as participating in gaze shift control. Recent evidence suggests, however, that other areas of the dorsomedial prefrontal cortex also influence gaze shift. Herein, we have investigated electrically evoked ear- and eye movements from the Premotor Ear-Eye Field, or PEEF (area 8B) of macaque monkeys. We stimulated PEEF during spontaneous condition (outside the task performance) and during the execution of a visual fixation task (VFT). In the first case, we functionally identified two regions within the PEEF: a core and a belt. In the core region, stimulation elicited forward ear movements; regarding the evoked eye movements, in some penetrations, stimulation elicited contraversive fixed-vectors with a mean amplitude of 5.14°; while in other penetrations, we observed prevalently contralateral goal-directed eye movements having end-points that fell within 15° in respect to the primary eye position. On the contrary, in the belt region, stimulation elicited backward ear movements; regarding the eye movements, in some penetrations stimulation elicited prevalently contralateral goal-directed eye movements having end-points that fell within 15° in respect to the primary eye position, while in the lateral edge of the investigated region, stimulation elicited contralateral goal-directed eye movements having end-points that fell beyond 15° in respect to the primary eye position. Stimulation during VFT either did not elicit eye movements or evoked saccades of only a few degrees. Finally, even though no head rotation movements were observed during the stimulation period, we viewed a relationship between the duration of stimulation and the neck forces exerted by the monkey's head. We propose an updated vision of the PEEF composed of two functional regions, core and belt, which may be involved in integrating auditory and visual information important to the programming of gaze orienting movements.

In equestrian show jumping, attention is particularly important to ensure maximum accuracy. Due to the anaerobic nature of the jumping and its requirement for precision coordination between human and horse, there may be a relation between the onset of lactic threshold and decrease in attention. In 12 healthy and injury-free equestrians (6 men, 6 women), the effects (blood lactate and glucose) of a show jumping course (250 m long with eight vertical obstacles with a height of 1.15 m height) on capacity and selectivity of attention was assessed. A typical reaction time paradigm and test of divided attention were administered. At the end of the course a significant increase of blood lactate was observed, whereas blood glucose did not significantly change. A deterioration of attention (intensity and selectivity) and a worsening of performance with increasing of blood lactate were observed. The present results led to the conclusion that the increase in blood lactate that occurs in riders executing a show jumping course is associated with worsening of both attentive capabilities and performance.

Psychological and physiological markers have been used to maximize competitive sport preparation. The aim of the present study was to evaluate the effects of two months of training and competitions on mood states and salivary cortisol diurnal variation in 15 female elite water polo players. The results demonstrated that the β coefficient values of the regression slope of cortisol values on sampling time was significantly flatter following the training period. The values of the area under the cortisol curve (AUC) 'with respect to ground' (AUCg) and those of the β coefficients of the slope of the diurnal change in cortisol levels were highly negatively correlated. The slope correlated positively with the dysfunctional Profile of Mood States scale and negatively with the functional scale. AUCg correlated negatively with dysfunctional factors and positively with the vigor index. These findings support the hypothesis that subclinical hypocortisolism and a flattened diurnal rhythm of cortisol may play a role in determining dysfunctional mood states.

The main purpose of the present investigation of 21 elite male swimmers was to assess whether the Ape Index (the ratio between the individual's arm span and height) and/or the second-to-fourth digit length ratio (2D:4D), i.e., the ratio between the length of the second and the fourth fingers of the right hand, are associated with the performance of high-level swimmers, when mood and/or executive function are covaried. The results showed no statistically significant correlation between the Ape Index and 2D:4D ratio, performance, executive function, or mood. In contrast, statistically significant correlations were found between 2D:4D ratio and performance, executive function, and mood. Regressions indicated that 2D:4D ratio and not Ape Index is related to the performances of a sample of male swimmers.

Blood levels of lactate and glucose were measured in 15 healthy male athletes with the purpose of evaluating possible correlation between their blood values and intensity and selectivity of attention, after a 30-min steady-state test performed at 60 and 80% of maximal oxygen consumption (VO2max). On the basis of the results, we conclude that, during aerobic exercise, a worsening of attentional capabilities does not occur unless there is an increase of blood lactate above 4 mmol/l.

Excitability of primary hand motor cortex (PHMC), evaluated with transcranial magnetic stimulation by using the "1 mV resting motor threshold" method, and capillary blood lactate were measured at the end, as well as 5 and 10 min after a fatiguing hand-grip exercise. The relation between blood lactate and the amplitudes of motor-evoked potentials showed a significant direct proportionality. Blood lactate seems to exert a protective role on PHMC against fatigue reduction during extremely intensive isometric exercises.

In the present paper, we examine the role of the cerebellar interpositus nucleus (IN) in motor and non-motor domains. Recent findings are considered, and we share the following conclusions: IN as part of the olivo-cortico-nuclear microcircuit is involved in providing powerful timing signals important in coordinating limb movements; IN could participate in the timing and performance of ongoing conditioned responses rather than the generation and/or initiation of such responses; IN is involved in the control of reflexive and voluntary movements in a task- and effector system-dependent fashion, including hand movements and associated upper limb adjustments, for quick effective actions; IN develops internal models for dynamic interactions of the motor system with the external environment for anticipatory control of movement; and IN plays a significant role in the modulation of autonomic and emotional functions.

The influence of blood lactate on brainstem excitability was tested by using the blink reflex (BR) recovery cycle on 18 sprinters. Blood lactate was measured before maximal cycling, at the end, as well as 5 and 10 min after the exhaustion. Blood lactate was associated with a decrement of R2 whereas only small changes were observed after an intravenous infusion of lactate. It seems, therefore, that lactate influences BR mainly by acting at the cortical level.

The aim of this study was to test the hypothesis that high levels of testosterone during prenatal life, testified by a low second-to-fourth digit ratio (2D:4D), as well as in adulthood affect the aggressive behavior of professional soccer players. Using 18 male professional players from a first level Italian Soccer Team we calculated: i) the 2D:4D ratio of the right hand, ii) the number of yellow and red cards per game, iii) the mean salivary testosterone concentration (Sal/T) and iv) the handling of aggressive impulses as assessed by the Picture Frustration test (PFT). Soccer players with a lower 2D:4D ratio had a higher number of fouls per game. A significant negative correlation was observed between Sal/T and 2D:4D ratio, as well as between 2D:4D ratio and the aggressiveness of players. By contrast, a significant positive correlation of Sal/T and fouls/game score and PFT was detected. No significant correlation was detected between 2D:4D or Sal/T and the playing position of players. Results of this study revealed that in professional soccer players, aggressive behavior, with the consequent increased risk of fouls during the game, is more likely to occur in individuals with high testosterone levels, not only in adulthood, but also during their intrauterine life.

The present study analyzed the in vitro effects induced by sodium L-lactate on human astrocytes and the SH-SY5Y cell line, when added at concentrations of 5, 10, and 25 mmol/liter. Expression of brain-derived neurotrophic factor (BDNF), inducible nitric oxide synthase (iNOS), and heat shock protein 70 kDa (HSP70) was evaluated by Western blot analysis. Cell viability with MTT, release of nitric oxide (NO) through the Griess reaction, and production of BDNF by enzyme-linked immunoassay was determined. Data indicate that, in SH-SY5Y as well as in cortical astrocytes, after 4 hr sodium L-lactate increases the expression and release of BDNF, iNOS, and NO; after 24 hr, it turns is ineffective for the production of the neurotrophin in SH-SY5Y and not in astrocytes, but the expression of iNOS and release of NO appear to be further increased compared with those after 4 hr. Sodium L-lactate influences differently the expression of HSP70 in SH-SY5Y compared with astrocytes. We propose, based on these findings, that sodium L-lactate affects the expression of BDNF in SH-SY5Y and astrocytes in a different manner: high levels of iNOS and NO expressed in SH-SY5Y have a profound inhibitory effect on the release of BDNF related to a more limited production of HSP70 by SH-SY5Y. In conclusion, the results demonstrate differences in the responses of SH-SY5Y and astrocytes to stimulation by high levels of sodium L-lactate. Sodium L-lactate differently and dose and time dependently influences the expression and release of BDNF, iNOS, NO, and HSP70 depending on the cell type., (Copyright © 2012 Wiley Periodicals, Inc.)

We have recently shown that covalent attachment of the nitric oxide (NO) moiety to the HIV protease inhibitor Saquinavir (Saq) produced a qualitatively new chemical entity, named Saquinavir-NO (Saq-NO), with enhanced anticancer properties and reduced toxicity both in vitro and in vivo. The aim of this study was to address several unanswered questions both on the pharmacological profile of Saq-NO as well as on the in vivo role of NO in the oncogenesis of A375 human melanoma cells. To this end, we have evaluated here the impact of single and combined effects of Saq-NO, Saq, the NO-donor DETA NONOate and the iNOS inhibitor L-NAME on the in vitro as well as in vivo growth of the iNOS positive A375 cells. Our data confirm clear-cut evidence for a strong and powerful anti-melanoma action of Saq-NO that is not duplicable by the combined use of Saq and DETA NONOate. Surprisingly, but also in agreement with the complex and multifaceted role of endogenous NO in A375 cells, both DETA NONOate and L-NAME significantly suppressed the in vivo growth of xenotransplants.

Aim: The present study was carried out with the aim to analyze the role of creatine on oxidative stress during exercise, i.e. whether creatine is a pro-oxidative or an antioxidant substance., Methods: In a randomized double-blind study involving 30 adult males, we examined plasma lactate, oxidative stress markers (malondialdehyde, MDA) and glutathione redox ratio (GSSG·GSH-1), antioxidative systems (vitamins A, E, C), and ergospirometric responses (respiratory quotient and relative oxygen uptake) before and after 30 min steady-state tests 75% VO2max (placebo and creatine)., Results: Ergospirometric tests, hematocrit values, blood lactate as well as vitamins A, E and C concentrations did not show significant differences between creatine and placebo testing. Conversely, oxidative stress markers MDA and GSSG·GSH-1 increased during placebo trials much more than in creatine trials., Conclusion: This is the first report documenting that a creatine loading, i.e., a 0.3 g/kg/die of creatine ingestion for 5 consecutive days, could reduce the oxidative stress, whereas its consumption may not have a clear metabolic advantage in certain aerobic activities.

Several data suggest that physical activity and cognitive stimulation have a positive effect on the quality of life (QoL) of people with Alzheimer's disease (AD), slowing the decline due to the disease. A pilot project was undertaken to assess the effect of cognitive stimulation, physical activity, and socialization on patients with AD and their informal caregiver's QoL and mood. Fourteen patients with AD were randomly divided into active treatment group and control group. At the end of treatment, a significant improvement in apathy, anxiety, depression, and QoL in the active treatment group was found. Considering caregivers, those of the active treatment group exhibited a significant improvement in their mood and in their perception of patients' QoL. This study provides evidence that a combined approach based on cognitive stimulation, physical activity, and socialization is a feasible tool to improve mood and QoL in patients with AD and their caregivers.

We studied the activity of single neurons in the pre-supplementary motor area (pre-SMA) of macaque monkeys as they performed two visuomotor tasks, called the visual fixation task and the visual fixation-blink task. Both tasks involved a sequence of three visual stimuli, red followed by yellow and green. The tasks differed in that the latter one had a gap within the period of the red stimulus, called a "blink". The tasks were performed in two modes, one of which included movements of both the arm and eye and the other of which involved only eye movements. In the arm-eye mode, the monkeys had to press a bar and fixate the red stimulus that appeared after bar press. To receive a reward, both the bar press and visual fixation had to be maintained until the green stimulus triggered bar release. In the eye mode, bar press and bar release were eliminated from the task. Of the 42 neurons active during the visual fixation task, 15 showed task-related activity in both arm-eye and eye modes, and our analysis focused on these cells. We found that the introduction of the blink in visual fixation-blink task abolished the task-related activity of these cells over the course of 2-4 trials. This finding suggests a role for the pre-SMA in reflecting progression of trials as an updating of motor instruction., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Prenatal androgens have important organizing effects on the development and future behavior of the brain. The second-to-fourth digit length ratio (2D:4D) has been proposed as a marker of these prenatal androgen effects, with a relatively longer fourth finger indicating higher prenatal androgen exposure. 2D:4D has been shown to predict the success of men who play sports and of financial traders. However, to date little is known regarding the effects of prenatal androgens on academic performance, for example, admission to and success in a highly competitive university system such as the state-run Italian medical schools. Here, we report the findings of a study conducted at the University of Catania Medical School, Italy, in which the 2D:4D ratio was sampled in a group of 48 male students. The 2D:4D ratios were found to be correlated with the performance of the students on the admission test to the medical school, their salivary testosterone levels and their aggressiveness; however, no correlation was observed with the mean score on exams during the course of study. Our results suggest that pre and/or postnatal androgens increase performance in situations that require prompt decision-making and the ability to take risks, but do not influence performance when a more analytical and planned approach is called for.

The aim of the present study was to examine the association of high blood lactate levels, induced with a maximal cycling or with an intravenous infusion, with spinal cord excitability. The study was carried out on 17 male athletes; all the subjects performed a maximal cycling test on a mechanically braked cycloergometer, while 6 of them were submitted to the intravenous infusion of a lactate solution (3 mg/kg in 1 min). Before the exercise or the injection, also at the end as well as 5 and 10 min after the conclusion, venous blood lactate was measured and excitability of the spinal α-motoneurons was evaluated by using the H reflex technique. In both experimental conditions, it has been observed that an exhaustive exercise is associated with a strong increase of blood lactate (but not of blood glucose) and with a significant reduction of spinal excitability. Since a similar augment of blood lactate induced by an intravenous infusion, in subjects not performing any exercise, is not associated with significant changes of spinal excitability, it can be concluded that the increase of blood lactate levels during a maximal exercise is not per se capable of modifying the excitability of spinal α-motoneurons.

Nitric oxide (NO) synthase (NOS) has been observed in the Cuneate Nuclei (CN), suggesting a role for NO in the modulation of their neurons' activity. The present study was undertaken to evaluate whether passive movement of forelimb as well as electric stimulation of medial nerve modulate the expression of neuronal isoform of NOS (nNOS) within CN. The experiments were carried out on 21 male Wistar rats, by using two different protocols. In the first group of rats the median nerve was stimulated with high frequency trains (phasic stimulation) or at constant frequency (tonic stimulation); as a control, in the third group, no stimulus was delivered. Moreover, in the second group of rats, we imposed to the animal's left forepaw circular paths at a roughly constant speed (continuous movement), or rapid flexions and extensions of the wrist (sudden movement); as a control, in the third group, no movement was imposed. After the experimental session, free-floating frontal sections of medulla oblongata were processed for nNOS or glutamate (GLU) immunohistochemistry. Phasic stimulation of the median nerve or sudden movements of the forelimb determines a significant decrement of the nNOS-positive neurons within the ipsilateral CN, whereas no effects were observed on GLU positive cells. We have also found a peculiar topographical distribution within IN of nNOS-positive neurons: positive cells were clustered at periphery of some "niches" having circular or elliptical form, with GLU positive cells at center.

Krabbe disease or globoid cell leukodystrophy is an autosomal recessively inherited disorder caused by the deficiency of galactocerebrosidase, the lysosomal enzyme that catalyzes the hydrolysis of galactose from galactosylceramide and galactosylsphingosine (psychosine). Psychosine accumulation results in the loss of myelin and oligodendrocytes in the brain of Krabbe patients as well as twitcher mice (natural model of human Krabbe disease). The aim of the present research was to investigate in twitcher mice the potential role of a diet deficient in galactose enriched in soy isoflavones and a pool of antioxidants molecules, such as l-glutathione, coenzyme Q10, xanthophylls, in counteracting the toxic effects derived by psychosine accumulation. A second goal of this manuscript was to demonstrate suppression of the apoptotic effects of psychosine in cultured oligodendrocyte progenitor mice cells (OLP-II) with antioxidants. The affected twitcher mice began the milk-derivatives free diet on post-natal day 15 although they also received mother's milk until post-natal day 18. Nevertheless, average life span was increased 50%, from 32+/-2 to 48+/-3 days, onset of tremor was delayed 17 days (from 21 days in the untreated twitcher mice to 38 days in the treated affected mice) and the gait in the treated mice was normal until almost a week after the untreated animals died (38+/-1 days versus 32 days at death). Weight gain in the treated animals also progressed to 38 days compared with 22 days for the untreated affected twitcher mice. Protection of the OLP-II cells against psychosine was shown using the MTT test (the ability of the tetrazolium salt MTT to form a dark blue formazan product by mitochondrial dehydrogenase in viable cells) and assay of expression of p53 and TNF-related apoptosis-inducing ligand (TRAIL). The results showed a time-dependent and concentration-dependent decrease of OLP-II viability on exposure to psychosine and dose-dependent protection with the antioxidants xanthophylls and glutathione. They also demonstrated that psychosine-induced p53 induction of apoptosis and TNF-related apoptosis-inducing ligand receptors could be decreased by l-glutathione and xanthophylls. A dietary approach may constitute a promising clinical management of the late-infantile and juvenile forms of Krabbe leukodystrophy., (Published by Elsevier Inc.)

The interpositus nucleus (IN) receives a large amount of sensory information from the limbs and, in turn, elaborates signals for movement control. In this paper, we tried to gather evidence on the possibility that neurons in the IN may elaborate sensory representations of the forelimb kinematics and, particularly, of the movement velocity vector. For this purpose, the forepaw of anesthetized rats was attached to a computer-controlled robot arm displaced passively along two types of trajectories (circular and figure eight), with the limb joints unconstrained. The firing activity of single cells was recorded and related to limb position and the two components of the movement velocity vector, namely, movement speed and direction. By using multiple regression analysis, we found that 12 out of 85 (14%) neurons were modulated by position, 18 out of 85 (21%) neurons were modulated by direction, 24 out of 85 (28%) neurons were modulated by movement speed, and 31 out of 85 (37%) neurons were sensitive to the full movement velocity vector. Most of the neurons modulated only by the speed component of the velocity vector (19 out of 24) were located in the posterior portion of the IN, whereas neurons in the anterior portion were mostly related to both components of the velocity vector. These results suggest that sensory information related to whole-limb movement velocity may be encoded by the IN, indicating also that the posterior interpositus may preferentially represent movement speed.

Recent studies have attempted to repair the damaged spinal cord (SC) by stimulating neurogenesis or neuroplasticity. Sonic hedgehog (Shh), Notch-1 and Numb are involved in the stem cell functioning. Additionally, Notch-1 has a role as modulator of synaptic plasticity. However, little is known about the role of these proteins in the adult SC after removal of motoneurons. In this study, we have injected cholera toxin-B saporin into the gastrocnemius muscle to induce a depletion of motoneurons within the lumbar SC of adult mice, and analysed the expression of choline acetyltransferase (ChAT), Synapsin-I, Shh, Notch-1 and Numb proteins. The functional outcome of the lesion was monitored by grid walk and rotarod tasks. The neurotoxin lesion determined a motoneuron depletion and a transient decrease of ChAT, Synapsin-I, Shh and Numb levels in the lumbar SC. ChAT was associated with Synapsin-I expression and motor performance at 1 week but not 1 month after lesion, suggesting that the recovery of locomotion could depend on synaptic plasticity, at least in an early phase. Shh and Notch-1 were associated with Synapsin-I levels, suggesting a role in modulating synaptic plasticity. Numb expression also appeared reduced after lesion and linked to motor performance. Moreover, unlike other lesion models, we observed glial reaction but no evidence of cell proliferation within the depleted SC. Given the mentioned roles of Shh, Notch-1 and Numb, we believe that an in vivo manipulation of their signalling after lesion could represent a suitable way to improve functional recovery by modulating synaptic plasticity and/or neurogenesis.

Neural representations of limb movement kinematic parameters are common among central nervous system structures involved in motor control, such as the interpositus nucleus of the cerebellum. Much experimental evidence indicates that neurons in the interpositus may encode limb kinematic parameters both during active, voluntary actions and during limb motion imposed passively, which entrains only sensory afferents. With respect to the sensory processing of information related to movement kinematics, we show that interpositus neuronal activity can parse out the directional from the scalar component (i.e., the movement speed) of the velocity vector. Moreover, a differential role for the anterior and posterior portion of interpositus in encoding these parameters emerged from these data, since the activity of the posterior interpositus was specifically associated to changes of movement speed. Limb movement representations in the interpositus nucleus may be instrumental for the control of goal-directed movements such as shaping hand during grasping or precise foot placement during gait. Finally, we discuss the idea that sensory information about the movement kinematics contribute to both feedback and anticipatory processes for limb movement control.

Gender differences in cortical excitability have been detected by using transcranial magnetic stimulation (TMS). The present study was carried out to compare the effects of high blood lactate levels, induced by performing a maximal exhausting exercise, on the excitability of the primary motor cortex in young male and female athletes. The study was carried out on 21 young males and 20 females from the Middle Distance Track Team of our university. Before the exercise, at the end, as well as 5 and 10 min after the conclusion, venous blood lactate and glucose were measured and excitability of the motor cortex was evaluated by using TMS. We observed a similar enhancement of excitability of primary motor cortex, concomitantly with an increase of blood lactate, in both young male and female athletes. However, the improvement was significantly higher (p < 0.05) in women (37.4% +/- 3.97) than in men (42.0% +/- 6.43), suggesting a greater sensitiveness of female cerebral cortex to blood lactate.

No information has yet been provided about the influence of blood lactate levels on the excitability of the cerebral cortex, in particular, of the motor cortex. The aim of the present study was to examine the effects of high blood lactate levels, induced with a maximal cycling or with an intravenous infusion, on motor cortex excitability. The study was carried out on 17 male athletes; all the subjects performed a maximal cycling test on a mechanically braked cycloergometer, whereas 6 of them were submitted to the intravenous infusion of a lactate solution (3 mg/kg in 1 min). Before the exercise or the injection, at the end, as well as 5 and 10 min after the conclusion, venous blood lactate was measured and excitability of the motor cortex was evaluated by using the transcranial magnetic stimulation. In both of these experimental conditions, it was observed that an increase of blood lactate is associated with a decrease of motor threshold, that is, an enhancement of motor cortex excitability. We conclude by hypothesizing that in the motor cortex the lactate could have a protective role against fatigue.

The accumulation of lactate in the blood after a high-intensity exercise is associated to an increase of lactate extractions by the brain. However, no information has been provided about the influences of blood lactate on cognitive performances and, in particular, on attention. The present study was carried out to examine the association of high blood lactate levels, induced with a maximal cycling, with two different attentional tasks. The study was carried out on 17 male sprinters who performed exhaustive exercise. Before the exercise, as well as 5 and 10 min after the exhaustion, blood lactate was measured and intensity as well as selectivity of attention of each subject were evaluated. Same measurements were performed on 6 out of 17 subjects who accepted to receive an intravenous infusion of a lactate solution. In both experimental conditions, an inverse relation between scores in both aspects of attention and blood lactate levels was observed.

The objective was to study whether repetitive transcranial magnetic stimulation (rTMS) of the motor cortex could induce modification of peripheral blood lactate values. Nineteen young healthy volunteers were included; during the study, all subjects were at rest, sitting on a comfortable armchair. The muscular activation was evaluated by continuous electromyographic record. TMS was performed by using a circular coil at the vertex. Resting motor threshold (rMT) was defined as the lowest TMS intensity able to induce motor responses of an amplitude >50 microV in the relaxed contralateral target muscle in approximately 50% of 20 consecutive stimuli. Venous blood lactate values were measured before, immediately after and 10 min after a single session of low frequencies (1Hz for 15 min) rTMS (LF rTMS) or high frequency (20 Hz for 15 min) rTMS (HF rTMS). As expected, LF rTMS induced a decrease of motor cortex excitability, whereas HF rTMS evoked an increase of motor cortex excitability. However, in the present investigation we observed that both conditions are associated to a significant increase of blood lactate. Since in our experimental conditions we can exclude a muscular production of lactate, the significant increment of peripheral blood lactate values, observed 10 min after the end of the rTMS session, is probably due to the crossing by brain-produced lactate of the blood-brain barrier.

Several evidences have demonstrated that adult mammals could achieve a wide range of spontaneous sensory-motor recovery after spinal cord injury by means of various forms of neuroplasticity. In this study we evaluated the possibility that after low-thoracic spinal cord hemisection in the adult rat, significant hindlimb locomotor recovery could occur, and that this recovery may be driven, at least in part, by mechanisms of synaptic plasticity. In order to address these issues, we measured the expression levels of synapsin-I and brain-derived neurotrophic factor by Western blotting, at various time points after hemisection and correlated them with the motor performance on a grid walk test. Regression analysis showed that the expression of synapsin-I was strongly correlated with the spontaneous recovery of hindlimb locomotion (R=0.78). Conversely, neither the expression levels of synapsin-I nor the locomotor recovery were associated with the expression of brain-derived neurotrophic factor. Overall results indicate that after spinal cord hemisection, substantial recovery of hindlimb locomotion could occur spontaneously, and that synaptic plasticity within spinal circuitries below the level of the lesion, could be an important mechanism involved in these processes.

Some neurons of main and external cuneate nuclei are immunoreactive for nitric oxide (NO) synthase, suggesting a role for endogenous NO in the early stages of somatosensory processing. We tested this hypothesis by investigating the possibility that NO modulates cuneate discharge. We observed that both spontaneous and N-methyl-D-aspartate-evoked activities of cuneate neurons were decreased by NO precursor L-arginine. The inhibition of NO synthase, by application of N-nitro-L-arginine methyl ester, instead, abolished the depressant effect induced by L-arginine. Our data suggest a NO modulation of cuneate neurons and provide support for a physiologic role not only in increasing the signal-to-noise ratio in the excited cells but also in a form of surround inhibition.

The present study was carried out to analyze the topography of bilateral spinal projections to the lateral reticular nucleus (LRN). We used retrograde transport of fluorescent tracers Fast Blue and Diamidino Yellow to identify spinal neurons projecting to the ipsilateral and/or contralateral LRN, as well as orthograde transport of Phaseolus vulgaris leucoagglutinin to identify the LRN areas where spinoreticular axons terminate. Orthograde labeling confirmed that bilateral spinoreticular projections coming from cervical and upper-thoracic segments terminate in the magnocellular division of LRN, while those coming from the lower-thoracic, lumbar and sacral segments end in the parvocellular division of the nucleus; only a sparse spinal input has been observed in the subtrigeminal division of LRN. Retrograde labeling showed that labeled neurons were present at all spinal levels and in particular large numbers in the cervical and lumbar enlargements. Retrogradely single-labeled cells were located, with contralateral predominance, in all segments of the spinal cord, within laminae IV, V, VI, VIII, and X, whereas in laminae III and VII labeled neurons were mainly observed ipsilaterally. Furthermore, a small fraction of double-labeled cells (7.4%) was observed throughout the spinal cord, mainly in laminae III, IV, VII and VIII.

The aim of this study is to verify, after recovery, the presence of specific patterns of cognitive dysfunctions in Transient Global Amnesia (TGA). Fourteen patients with the diagnosis of TGA were submitted to a battery of neuropsychological tests and compared to a matched control group. We found significant qualitative and quantitative differences between TGA patients and controls in the California Verbal Learning Test (CLVT) and Rey-Osterrieth Complex Figure Test. Our data support the presence of selective cognitive dysfunctions after the clinical recovery. Moreover, for Verbal Fluency, Digit Span Backward, and Number of Clusters in the CVLT short-term memory test, the relation resulted as positively related with the temporal interval from the TGA episode. Reduction of categorical learning, attention, and qualitative alterations of spatial strategy seem to postulate a planning defect due to a prefrontal impairment.

Neuroplasticity represents a common phenomenon after spinal cord (SC) injury or deafferentation that compensates for the loss of modulatory inputs to the cord. Neurotrophins play a crucial role in cell survival and anatomical reorganization of damaged spinal cord, and are known to exert an activity-dependent modulation of neuroplasticity. Little is known about their role in the earliest plastic events, probably involving synaptic plasticity, which are responsible for the rapid recovery of hindlimb motility after hemisection, in the rat. In order to gain further insight, we evaluated the changes in BDNF and NT-4 expression by lumbar motoneurons after low-thoracic spinal cord hemisection. Early after lesion (30 min), the immunostaining density within lumbar motoneurons decreased markedly on both ipsilateral and contralateral sides of the spinal cord. This reduction was statistically significant and was then followed by a significant recovery along the experimental period (14 days), during which a substantial recovery of hindlimb motility was observed. Our data indicate that BDNF and NT-4 expression could be modulated by activity of spinal circuitry and further support putative involvement of the endogenous neurotrophins in mechanisms of spinal neuroplasticity.

In this paper, we review single and multijoint studies that, over the years, have provided insight on the cerebellar encoding of limb spatial position. In particular, we present support to the idea that the cerebellum integrates signals from multiple sources to encode global limb parameters. Then, we highlight the result of recent studies that analyzed quantitatively the relationships between limb end-point position and cerebellar activity. These findings suggest that the cerebellum may share with other central sensory-motor structures an anisotropic representation of limb position characterized by a strong bias along the anteroposterior axis. Finally, we speculate that this anisotropy may also subtend an internal representation of limb mechanics.

The aim of the present study was to investigate the effects of Levetiracetam, a new antiepileptic drug, on the synthesis of brain-derived neurotrophic factor (BDNF) and inducible nitric oxide synthase (iNOS) in rat cortical astrocyte cultures. The astrocytes were treated for 48 h with different concentrations of Levetiracetam and the expression of BDNF and iNOS was analyzed by immunostaining and immunoblotting analyses. We observed that Levetiracetam is able to stimulate expression of both BDNF and iNOS in a concentration-dependent manner on rat cortical astrocyte cultures. For the BDNF, this effect appears at very low concentrations (1 and 10 microgram/ml), while expression of iNOS appears only at higher dosages (50 microgram/ml). We conclude that Levetiracetam might exert neuroprotective effects, at least in part, via stimulation of neurotrophic factors, thus reducing the extent of inflammation and neuronal death under pathological conditions such as epilepsy.

The relationship between the spatial location of limb and the activity of cerebellar neurons has received little attention and its nature still remains ambiguous. To address this question we studied the activity of Purkinje and nucleus interpositus cells in relation to the spatial location of rat forelimb. A computer-controlled robot arm displaced the limb passively across 15 positions distributed on a parasagittal plane. The limb was upheld for 8 s in each position, which was identified by the Cartesian coordinates of the forepaw. We selected the neurons whose activities were significantly modulated by forepaw position and found that the majority represented preferentially one spatial dimension of the Cartesian plane both in the cerebellar cortex and nucleus interpositus. In particular, the antero-posterior axis was best represented in cerebellar neuronal discharges. This result suggests that the intermediate part of the cerebellum might encode limb position by way of an anisotropic representation of the spatial coordinates of the limb end-point.

We examined the role of main and external cuneate nuclei neurons in processing sensory information during forelimb passive movement. We recorded activity of neurons using circular and figure-eight trajectories, at different speeds, in anaesthetized rats. A multivariate regression analysis was performed to correlate neural discharge to movement direction and speed, the two components of the velocity vector. We found that the activity of the majority of cuneate neurons related to passive movement velocity and that the directional component of the velocity vector accounted for a larger fraction of the variability in the firing rate than the scalar component (speed). These results indicate that cuneate cells can process whole limb afferent information to elaborate a representation of the movement velocity vector.

The present study was undertaken to analyze the effects on unitary activity of inferior olive (IO) neurons elicited by activation of cerebellar lateral nucleus (LN), in rats submitted to the chronic destruction of MDJ structures, i.e. in animals in which the LN-evoked effects in IO should be depended only on activation of GABAergic cells of LN. It has been observed that about two-thirds of the olivocerebellar neurons are significantly affected by LN stimulation, and > 68% of those cells were inhibited. Two-thirds of the inhibitory responses were compatible with a monosynaptic linkage, whereas the remaining inhibitions were probably due to polisynaptic linkages. The majority of LN-induced inhibitions was abolished or greatly reduced following application of GABA antagonists.

We studied in vitro the effects of anticonvulsant drugs Gabapentin and Topiramate on the production of reactive oxygen species and nitric oxide (NO), the activity of glutamine synthetase (GS), and cell viability in primary cultures of rat cortical astrocytes which are intimately involved in the normal functioning of neurons. We investigated the effects of these drugs at concentrations within the therapeutic range (1, 10 and 50 microg/ml). We observed that, in cultured astrocytes, Gabapentin induced a weak increase in the biosynthesis of NO, a mild decrease in GS activity and cell viability, and minor induction of a stress condition. Topiramate was observed to induce even greater stressor effects on these cells.