iron metabolism modification during repeated show jumping event in equine athletes

Abstract In athletic horse the evaluation of iron status is of great importance to improve physical performance and health status of animal. The aim of this study was to evaluate the changes of iron indices following show jumping. Ten regularly trained Italian Saddlebred horses aged 7-8 years (mean body weight 467±12 kg) were subjected to three days jumping competition. Blood samples were collected at 5 time points: T0 (the day before competitions), T1 (immediately after exercise at day 1), T2 (immediately after exercise at day 2), T3 (immediately after exercise at day 3) and during the recovery period T4 (24 h after day 3). On each blood sample the values of red blood cell (RBC), hemoglobin concentration (Hb), hematocrit (Hct), serum iron, ferritin, transferrin, total iron-binding capacity (TIBC) and unsaturated iron-binding capacity (UIBC) were assessed. One-way repeated measure analysis of variance (ANOVA) showed a statistical significant effect of exercise (P<0.05) on all studied parameters. The application of Bonferroni's post-hoc comparison showed a statistical significant increase in all studied parameters after exercise. These results provide new information about the changes in iron profile of jumper horse following exercise allowing for better evaluation of the health status and physical performance of this athlete horse

Constrained spherical deconvolution provides evidence of extensive subcortical direct cerebellumbasal ganglia connections in human brain

Traditionally, the basal ganglia (BG) are thought to play a major role in the selection and inhibition of motor commands, while the cerebellum plays a role in tuning and reshaping on-going movement. In the past, the connections between the cerebellum and the cerebral cortex have been considered to be anatomically and functionally distinct from those linking the BG with the cerebral cortex. Evidences from recent anatomical experiments, using retrograde transneuronal transport of rabies virus in macaques, have challenged this old perspective demonstrating disynaptic subcortical pathways that directly link the cerebellum with the BG. Since the application of these techniques to the human brain remains elusive, due to the invasive nature of such methods, whether and to what extent these specific connections between the BG and cerebellum exist in the human brain remains unclear. However, recent developments in Diffusion Magnetic Resonance Imaging (dMRI) and diffusion tractography may allow for non-invasive and in vivo studies of the anatomical substrate of basal ganglia systems. Indeed, in our previous paper we studied the basal ganglia connectome providing strong evidences of a direct connection from cortex to Globus Pallidum (GPe and GPi) [1]. Thirteen normal subjects with no history of any overt neurological and/or psychiatric disorders were examined to test the hypotheses that substantial interactions, at least on the level shown in animal studies, also exist in the human brain. We demonstrated that it is feasible to disclose these cerebellar-subcortical connections by using constrained spherical deconvolution (CSD), an innovative approach which allows a reliable reconstruction of small- and long-fiber pathways, with subvoxel resolution in brain regions with multiple fiber orientations [2]. In particular we found evidences of subthalamic-cerebellar, dentate-thalamo-striatal, dentate-rubral-thalamic, dentate-rubral-pallidal and dentate-nigral connections. In addition to these connections, we found a direct cerebellar-dentate-pallidal connection never reported in literature to our knowledge; we identified and isolated two well-distinct tracts presenting an ipsilateral and contralateral component, converging mainly on the antero-medial part of the globus pallidus

Integrins in masseter muscle in unilateral crossbite patients: an immunohistochemical and molecular study

Integrins are a large family of transmembrane heterodimeric receptors that play a key role in cell adhesion, differentiation, remodelling and tissue repair. b1D isoform is detected only in skeletal and cardiac muscle, while very low amounts of b1A were detected by immunoblot in striated muscles. b1D isoform was associated with a7A and a7B in adult skeletal muscle. Although many studies have been performed on the integrins in adult skeletal muscle, insufficient data exist on behaviour of these proteins in masseter muscle. About this muscles it was demonstrated that they have several differences in respect to limb and trunk muscles. Generally, fibers in the masseter muscle are smaller than fibers in limb and trunk muscles. Consequently, the smaller muscle fibers may be advantageous for the jaw muscles. On this basis, we performed an immunohistochemical and molecular study in order to analyze the behaviour of integrins in normal masseter muscle of both side; moreover, to better comprehend the role of these proteins, we also analyzed masseter muscles of patients affected by unilateral crossbite. Interestingly, our result, integrating with astatistical analysis, showed that, on patients affected by right crossbite, the integrins are substantially less, in both masseters, than those observed in control subjects; in right masseter, the amount of integrin appeared less than the amount of integrins detected in left counterpart. Since kinematics and electromyography study have been demonstrated that masseters of the crossbite side were less active than non-affected side, our results, showing a decrease of integrins in the masseter of crossbite side, allow to hypothesize that the integrins, and in particular alfa7A and beta1A integrins, could play a crucial role in the control of contraction activity

The cerebellum-periaqueductal gray connectivity: a constrained spherical deconvolution tractography study

The periaqueductal gray (PAG) is a relevant neuronal station situated in the midbrain, which play a pivotal role in triggering behavioral responses to stressful stimuli, such as pain or threat. Current knowledge concerning PAG functions is based on several tract-tracing studies conducted on animals, which unveiled PAG connectivity to both cortical and subcortical areas [1]. Considering that descending projections to spinal cord reach the dorsal horn and connections to motor related cortical areas have never been described yet, the neural structure which best fits PAG modulation of motor behavior is the cerebellum. Direct connections between PAG and cerebellar cortex were firstly described in cats and neurophysiological studies conducted on animals, suggesting either direct or undirect PAG influence to cerebellar activity. In the last decades, the rise of diffusion weighted imaging and tractography have made possible to reliably reconstruct white matter pathways in the human brain. To the best of our knowledge, few tractography studies explored PAG connectivity in humans and the evidences concerning direct or undirect connections with the cerebellar cortex are still sparse. Aimed at investigating PAG connectivity with particular focus on PAG-cerebellum connections, we used high quality diffusion weighted imaging data of thirty healthy subjects from the Human Connectome Project. Fiber tracts have been reconstructed using Spherical Informed Filtering of Tractograms, a novel algorithm improving streamline reconstruction and selection [2]. Connectivity analysis revealed that the PAG is mainly connected with subcortical structures, such as the thalamus and the cerebellum. Taken together our results show a direct interplay between the PAG and the cerebellum, thus suggesting the cerebellum as a likely candidate to modulate complex features of motor behavior in stressful conditions, such as adaptation after social defeat and computing strategies to avoid threatening situations

Sarcoglycans and gabaa receptors in rat central nervous system: an immunohistochemical study

Sarcoglycan subcomplex is a transmembrane glycoprotein system which connects extracellular matrix to cytoskeleton. Although this complex has been found in several non-muscular tissues, no data exist about a sarcoglycan subcomplex in brain. Only the presence of ε-sarcoglycan in brain has been described in detail because its mutation determines Myoclonus Dystonia Syndrome. Also ζ-, β- and δ-sarcoglycans have been found in brain but only at mRNA level and their distribution in brain is still unknown. Here, we have searched for the expression of all sarcoglycans in specific brain regions of rat as hippocampus, cerebral and cerebellar cortex. Since a correlation between dystrophin glycoprotein complex and γ-amino butyric acid A (GABAA) receptor was demonstrated, we have investigated also a possible colocalization between sarcoglycans and GABAA receptor. Results have shown that all sarcoglycans are expressed in neurons of all observed regions; these proteins show a spot-like pattern of fluorescence and are mainly localized at soma level. Moreover, each sarcoglycan colocalizes with GABAA receptor. The present study shows, for the first time, the expression of all sarcoglycans in brain; moreover, the prevalent localization of sarcoglycans at post-synaptic level and the colocalization of these glycoproteins with GABAA receptor suggests that sarcoglycans play a key role in central nervous system, regulating post-synaptic receptors assembly

Painting a global picture of basal ganglia network: from past to present!

Since the 70s it has been thought that basal ganglia integrated sensorimotor, associative and limbic inputs and then projected this information through the thalamus to the motor cortex, supplementary motor area and frontal cortex, thus playing a relevant role in planning movement. Recent literature on basal ganglia networks is going beyond the classical “dogma” of dorsal striatum as the main station for cortical inputs in basal ganglia loops and several neurophysiological studies have suggested a more segregated organization of these neural circuits. In the classical view, various tract-tracing methods combined with immunohistochemistry and in situ hybridization demonstrated that the cortical information flows through the basal ganglia via a dual-network model, based on the “direct” and “indirect” routes. However, in addition to these two major projection systems, a glutamatergic hyper-direct pathway between cerebral cortex and subthalamic nucleus has been demonstrated first in monkeys and then in humans. Furthermore, we have recently shown a i) cortico-pallidal connection; ii) a cerebello-pallidal connection; iii) a cerebello nigral connection [1, 2]. Herein, we extensively examined basal ganglia network of fifteen healthy subjects by using probabilistic constrained spherical deconvolution tractography on magnetic resonance diffusion weighted imaging data and we also performed weighted connectivity analysis for each of the subcortical nuclei. In addition, we demonstrated for the first time tractographic evidences of the existence of a direct cortico-nigral pathway in humans. We found that substantia nigra is connected with cerebral cortex as a whole, with the most representative connections involving prefrontal cortex, precentral and postcentral gyri and superior parietal lobule. These findings would strength the hypothesis that the cortico-basal ganglia network consists of several, parallel, segregated, and functionally distinct, but homologous loop, and may be relevant for the comprehension of the pathophysiology of several basal ganglia disorders

The Olfactory System Revealed: Non-Invasive Mapping by using Constrained Spherical Deconvolution Tractography in Healthy Humans

Although the olfactory sense has always been considered with less interest than the visual, auditive or somatic senses, it does plays a major role in our ordinary life, with important implication in dangerous situations or in social and emotional behaviors. Traditional Diffusion Tensor signal model and related tractography have been used in the past years to reconstruct the cranial nerves, including the olfactory nerve (ON). However, no supplementary information with regard to the pathways of the olfactory network have been provided. Here, by using the more advanced Constrained Spherical Deconvolution (CSD) diffusion model, we show for the first time in vivo and non-invasively that, in healthy humans, the olfactory system has a widely distributed anatomical network to several cortical regions as well as to many subcortical structures. Although the present study focuses on an healthy sample size, a similar approach could be applied in the near future to gain important insights with regard to the early involvement of olfaction in several neurodegenerative disorders

Nat Metab.

Bile acids (BAs) are signalling molecules that mediate various cellular responses in both physiological and pathological processes. Several studies report that BAs can be detected in the brain1, yet their physiological role in the central nervous system is still largely unknown. Here we show that postprandial BAs can reach the brain and activate a negative-feedback loop controlling satiety in response to physiological feeding via TGR5, a G-protein-coupled receptor activated by multiple conjugated and unconjugated BAs2 and an established regulator of peripheral metabolism3,4,5,6,7,8. Notably, peripheral or central administration of a BA mix or a TGR5-specific BA mimetic (INT-777) exerted an anorexigenic effect in wild-type mice, while whole-body, neuron-specific or agouti-related peptide neuronal TGR5 deletion caused a significant increase in food intake. Accordingly, orexigenic peptide expression and secretion were reduced after short-term TGR5 activation. In vitro studies demonstrated that activation of the Rho–ROCK–actin-remodelling pathway decreases orexigenic agouti-related peptide/neuropeptide Y (AgRP/NPY) release in a TGR5-dependent manner. Taken together, these data identify a signalling cascade by which BAs exert acute effects at the transition between fasting and feeding and prime the switch towards satiety, unveiling a previously unrecognized role of physiological feedback mediated by BAs in the central nervous system.Développment d'une infrastructure française distribuée coordonnéeLa signalisation des acides biliaires dans le cerveau et son rôle dans le contrôle métaboliqueInnovations instrumentales et procédurales en psychopathologie expérimentale chez le rongeu