Does MPTP intoxication in mice induce metabolite changes in the nucleus accumbens? A 1H nuclear MRS study: A severe DA denervation in VTA induces metabolite changes in the NAc

International audienceUsing in vivo 1H NMR spectroscopy in a mouse model of Parkinson's disease, we previously showed that glutamate concentrations in the dorsal striatum were highest after dopamine denervation associated with an increase in gamma-aminobutyric acid (GABA) and (Gln) glutamine levels. The aim of this study was to determine whether the changes previously observed in the motor part of the striatum were reproduced in a ventral part of the striatum, the nucleus accumbens (NAc). This study was carried out on controls and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. In vivo spectra were acquired for a voxel (8 L) in the dorsal striatum, and in the NAc (1.56 L). NMR acquisitions were first performed 10 days after the last MPTP injection in a basal condition [after saline intraperitoneal (i.p.) injection] and then in the same animal the week after basal NMR acquisitions, after acute levodopa administration (200 mg kg1, i.p.). Immunohistochemistry was used to determine the levels of (Glu) glutamate, glutamine synthetase (GS) and glutamic acid decarboxylase (GAD) isoform 67 in these two structures. The Glu, Gln and GABA concentrations obtained in the basal state were higher in the NAc of MPTP-intoxicated mice which have the higher dopamine denervation in the ventral tegmental area (VTA) and in the dorsal striatum. Levodopa decreased the levels of these metabolites in MPTP-intoxicated mice to levels similar to those in controls. In parallel, immunohistochemical staining showed that glutamate, GS and GAD67 immunoreactivity increased in the dorsal striatum of MPTP-intoxicated mice and in the NAc for animals with a severe dopamine denervation in VTA. These findings strongly supported a hyperactivity of the glutamatergic cortico-striatal pathway and changes in glial activity when the dopaminergic denervation in the VTA and substantia nigra pars compacta (SNc) was severe. Copyright (c) 2012 John Wiley & Sons, Ltd

Chronic pramipexole treatment increases tolerance for sucrose in normal and ventral tegmental lesioned rats.

The loss of dopamine neurons observed in Parkinson's disease (PD) elicits severe motor control deficits which are reduced by the use of dopamine agonists. However, recent works have indicated that D3-preferential agonists such as pramipexole can induce impulse control disorders (ICDs) such as food craving or compulsive eating. In the present study, we performed an intermittent daily feeding experiment to assess the effect of chronic treatment by pramipexole and VTA bilateral lesion on tolerance for sucrose solution. The impact of such chronic treatment on spontaneous locomotion and spatial memory was also examined. Changes in sucrose tolerance could indicate the potential development of a change in food compulsion or addiction related to the action of pramipexole. Neither the bilateral lesion of the VTA nor chronic treatment with pramipexole altered the spontaneous locomotion or spatial memory in rats. Rats without pramipexole treatment quickly developed a stable intake of sucrose solution in the 12 h access phase. On the contrary, when under daily pramipexole treatment, rats developed a stronger and ongoing escalation of their sucrose solution intakes. In addition, we noted that the change in sucrose consumption was sustained by an increase of the expression of the Dopamine D3 receptor in the core and the shell regions of the nucleus accumbens. The present results may suggest that long-term stimulation of the Dopamine D3 receptor in animals induces a strong increase in sucrose consumption, indicating an effect of this receptor on certain pathological aspects of food eating.journal article20142015 01 06importe

Kératodermie palmo-plantaire de Nagashima : une kératodermie palmo-plantaire méconnue en Europe

BACKGROUND: Herein we present a case of palmoplantar keratoderma (PPK) in a young adopted girl of Chinese origin living in France. OBSERVATION: The patient, aged six years, had presented transgressive PPK since birth, as well as erythema progressing in congestive inflammatory episodes, palmoplantar hyperhidrosis and progressive characteristics (moderate hyperkeratosis in areas of rubbing other than the palms and soles, namely the elbows and knees). Histopathological examination of a skin biopsy revealed a thick epidermis with lengthening and thickening of crests. The epithelium displayed a thick granular layer. Electron microscopy showed hyperorthokeratosis with hypergranulosis and loss of lamellar structure of the keratinosomes, as well as cleavage between corneocytes. Molecular studies showed the presence of two composite heterozygous mutations of the SERPINB7 gene, enabling a diagnosis of Nagashima-type PPK (NPPK) to be made. DISCUSSION: NPPK is an autosomal recessive disease caused by a mutation in the SERPINB7, a member of the superfamily of serine protease inhibitors. It was described by Nagashima in 1977 with molecular characterisation by Kubo following in 2013. It is the most widespread form of PPK in Asia (with a prevalence of 1.2/10,000 in Japan and 3.1/10,000 in China). It is distinguished from the other PPKs in terms of transgressive soft hyperkeratosis, inflammatory episodes and hyperhidrosis, as well as by its non-progressive nature. In the present case, while the clinical presentation was characteristic, diagnosis was only made thanks to sequencing of a panel of over 50 genes responsible for PPK. The disease is effectively little-known in Europe. This study highlights the increasing importance of diagnostic investigation methods involving the use of gene panels

Kératodermie palmo-plantaire de Nagashima : une kératodermie palmo-plantaire méconnue en Europe

BACKGROUND: Herein we present a case of palmoplantar keratoderma (PPK) in a young adopted girl of Chinese origin living in France. OBSERVATION: The patient, aged six years, had presented transgressive PPK since birth, as well as erythema progressing in congestive inflammatory episodes, palmoplantar hyperhidrosis and progressive characteristics (moderate hyperkeratosis in areas of rubbing other than the palms and soles, namely the elbows and knees). Histopathological examination of a skin biopsy revealed a thick epidermis with lengthening and thickening of crests. The epithelium displayed a thick granular layer. Electron microscopy showed hyperorthokeratosis with hypergranulosis and loss of lamellar structure of the keratinosomes, as well as cleavage between corneocytes. Molecular studies showed the presence of two composite heterozygous mutations of the SERPINB7 gene, enabling a diagnosis of Nagashima-type PPK (NPPK) to be made. DISCUSSION: NPPK is an autosomal recessive disease caused by a mutation in the SERPINB7, a member of the superfamily of serine protease inhibitors. It was described by Nagashima in 1977 with molecular characterisation by Kubo following in 2013. It is the most widespread form of PPK in Asia (with a prevalence of 1.2/10,000 in Japan and 3.1/10,000 in China). It is distinguished from the other PPKs in terms of transgressive soft hyperkeratosis, inflammatory episodes and hyperhidrosis, as well as by its non-progressive nature. In the present case, while the clinical presentation was characteristic, diagnosis was only made thanks to sequencing of a panel of over 50 genes responsible for PPK. The disease is effectively little-known in Europe. This study highlights the increasing importance of diagnostic investigation methods involving the use of gene panels

Mapping the contribution of single muscles to facial movements in the rhesus macaque

The rhesus macaque (Macaca mulatta) is the most utilized primate model in the biomedical and psychological sciences. Expressive behavior is of interest to scientists studying these animals, both as a direct variable (modeling neuropsychiatric disease, where expressivity is a primary deficit), as an indirect measure of health and welfare, and also in order to understand the evolution of communication. Here, intramuscular electrical stimulation of facial muscles was conducted in the rhesus macaque in order to document the relative contribution of each muscle to the range of facial movements and to compare the expressive function of homologous muscles in humans, chimpanzees and macaques. Despite published accounts that monkeys possess less differentiated and less complex facial musculature, the majority of muscles previously identified in humans and chimpanzees were stimulated successfully in the rhesus macaque and caused similar appearance changes. These observations suggest that the facial muscular apparatus of the monkey has extensive homology to the human face. The muscles of the human face, therefore, do not represent a significant evolutionary departure from those of a monkey species. Thus, facial expressions can be compared between humans and rhesus macaques at the level of the facial musculature, facilitating the systematic investigation of comparative facial communication

Applications of Chemical Shift Imaging to Marine Sciences

The successful applications of magnetic resonance imaging (MRI) in medicine are mostly due to the non-invasive and non-destructive nature of MRI techniques. Longitudinal studies of humans and animals are easily accomplished, taking advantage of the fact that MRI does not use harmful radiation that would be needed for plain film radiographic, computerized tomography (CT) or positron emission (PET) scans. Routine anatomic and functional studies using the strong signal from the most abundant magnetic nucleus, the proton, can also provide metabolic information when combined with in vivo magnetic resonance spectroscopy (MRS). MRS can be performed using either protons or hetero-nuclei (meaning any magnetic nuclei other than protons or 1H) including carbon (13C) or phosphorus (31P). In vivo MR spectra can be obtained from single region of interest (ROI or voxel) or multiple ROIs simultaneously using the technique typically called chemical shift imaging (CSI). Here we report applications of CSI to marine samples and describe a technique to study in vivo glycine metabolism in oysters using 13C MRS 12 h after immersion in a sea water chamber dosed with [2-13C]-glycine. This is the first report of 13C CSI in a marine organism

Elevated Pontine and Putamenal GABA Levels in Mild-Moderate Parkinson Disease Detected by 7 Tesla Proton MRS

Background: Parkinson disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons. However, postmortem evidence indicates that the pathology of lower brainstem regions, such as the pons and medulla, precedes nigral involvement. Consistently, pontomedullary damage was implicated by structural and PET imaging in early PD. Neurochemical correlates of this early pathological involvement in PD are unknown. Methodology/Principal Finding: To map biochemical alterations in the brains of individuals with mild-moderate PD we quantified neurochemical profiles of the pons, putamen and substantia nigra by 7 tesla (T) proton magnetic resonance spectroscopy. Thirteen individuals with idiopathic PD (Hoehn & Yahr stage 2) and 12 age- and gender-matched healthy volunteers participated in the study. c-Aminobutyric acid (GABA) concentrations in the pons and putamen were significantly higher in patients (N = 11, off medications) than controls (N = 11, p,0.001 for pons and p,0.05 for putamen). The GABA elevation was more pronounced in the pons (64%) than in the putamen (32%). No other neurochemical differences were observed between patients and controls. Conclusion/Significance: The GABA elevation in the putamen is consistent with prior postmortem findings in patients with PD, as well as with in vivo observations in a rodent model of PD, while the GABA finding in the pons is novel. The more significant GABA elevation in the pons relative to the putamen is consistent with earlier pathological involvement of th

Assessing brain function in stressed healthy individuals following the use of a combination of green tea, Rhodiola, magnesium, and B vitamins: an fMRI study

IntroductionThis randomized, controlled, single-blinded trial assessed the effect of magnesium (Mg)-Teadiola (Mg, vitamins B6, B9, B12, Rhodiola, and green tea/L-theanine) versus placebo on the brain response to stressful thermal stimulus in chronically stressed, but otherwise healthy subjects. Impacts on stress-related quality-of-life parameters (depression, anxiety, sleep, and perception of pain) were also explored.MethodsThe study recruited a total of 40 adults (20 per group), suffering from stress for more than 1 month and scaling ≥14 points on the Depression Anxiety Stress Scale (DASS)-42 questionnaire at the time of inclusion. Individuals received oral Mg-Teadiola or placebo for 28 days (D). fMRI analysis was used to visualize the interplay between stress and pain cerebral matrices, using thermal stress model, at baseline (D0) and after D28.ResultsBased on blood-oxygen-level-dependent (BOLD) signal variations during the stress stimulation (before pain perception), a significantly increased activation between D0 and D28 was observed for left and right frontal area (p = 0.001 and p = 0.002, respectively), left and right anterior cingulate cortex (ACC) (p = 0.035 and p = 0.04, respectively), and left and right insula (p = 0.034 and p = 0.0402, respectively) in Mg-Teadiola versus placebo group. During thermal pain stimulation, a significantly diminished activation of the pain matrix was observed between D0 and D28, for left and right prefrontal area (both p = 0.001), left and right insula (p = 0.008 and p = 0.019, respectively), and left and right ventral striatum (both p = 0.001) was observed in Mg-Teadiola versus placebo group. These results reinforce the clinical observations, showing a perceived benefit of Mg-Teadiola on several parameters. After 1 month of treatment, DASS-42 stress score significantly decreased in Mg-Teadiola group [effect size (ES) −0.46 (−0.91; −0.01), p = 0.048]. Similar reductions were observed on D14 (p = 0.011) and D56 (p = 0.008). Sensitivity to cold also improved from D0 to D28 for Mg-Teadiola versus placebo [ES 0.47 (0.02; 0.92) p = 0.042].ConclusionSupplementation with Mg-Teadiola reduced stress on D28 in chronically stressed but otherwise healthy individuals and modulated the stress and pain cerebral matrices during stressful thermal stimulus