Modulation of Brain β-Endorphin Concentration by the Specific Part of the Y Chromosome in Mice

International audienceBackground: Several studies in animal models suggest a possible effect of the specific part of the Y-chromosome (Y NPAR) on brain opioid, and more specifically on brain b-endorphin (BE). In humans, male prevalence is found in autistic disorder in which observation of abnormal peripheral or central BE levels are also reported. This suggests gender differences in BE associated with genetic factors and more precisely with Y NPAR. Methodology/Principal Findings: Brain BE levels and plasma testosterone concentrations were measured in two highly inbred strains of mice, NZB/BlNJ (N) and CBA/HGnc (H), and their consomic strains for the Y NPAR. An indirect effect of the Y NPAR on brain BE level via plasma testosterone was also tested by studying the correlation between brain BE concentration and plasma testosterone concentration in eleven highly inbred strains. There was a significant and major effect (P,0.0001) of the Y NPAR in interaction with the genetic background on brain BE levels. Effect size calculated using Cohen's procedure was large (56% of the total variance). The variations of BE levels were not correlated with plasma testosterone which was also dependent of the Y NPAR. Conclusions/Significance: The contribution of Y NPAR on brain BE concentration in interaction with the genetic background is the first demonstration of Y-chromosome mediated control of brain opioid. Given that none of the genes encompassed by the Y NPAR encodes for BE or its precursor, our results suggest a contribution of the sex-determining region (Sry, carried by Y NPAR) to brain BE concentration. Indeed, the transcription of the Melanocortin 2 receptor gene (Mc2R gene, identified as the proopiomelanocortin receptor gene) depends on the presence of Sry and BE is derived directly from proopiomelanocortin. The results shed light on the sex dependent differences in brain functioning and the role of Sry in the BE system might be related to the higher frequency of autistic disorder in males

Precise mapping of the magnetic field in the CMS barrel yoke using cosmic rays

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2010 IOPThe CMS detector is designed around a large 4 T superconducting solenoid, enclosed in a 12 000-tonne steel return yoke. A detailed map of the magnetic field is required for the accurate simulation and reconstruction of physics events in the CMS detector, not only in the inner tracking region inside the solenoid but also in the large and complex structure of the steel yoke, which is instrumented with muon chambers. Using a large sample of cosmic muon events collected by CMS in 2008, the field in the steel of the barrel yoke has been determined with a precision of 3 to 8% depending on the location.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Tachykinin-Immunoreactive Neurons in Developing Feline Neostriatum: Somatodendritic Morphogenesis Demonstrated by Combined Immunohistochemistry/Golgi Impregnation-Gold Toning

This investigation was designed to survey and characterize the development of a key link between chemically mediated neurotransmission and neuronal cytoarchitecture in mammalian basal ganglia. Peroxidase immunohistochemical and Golgi impregnation/gold toning methods were combined to doubly label the tachykinin neuromodulator signature and somatodendritic structure of neostriatal neurons in late fetal, postnatal and adult cats. The results supported 3 conclusions of considerable significance. (1) Colocalization of immunohistochemical and Golgi impregnation/gold toning labels is a feasible, rational and productive means to identify and determine the somatodendritic morphogenesis of tachykinin neurons. (2) The application of this method to developing feline neostriatum demonstrates directly that the principal tachykinin cells are medium-sized spiny neurons, which undergo progressive growth and elaboration of cell bodies, dendritic arbors and dendritic spines during the late fetal and postnatal periods. (3) There is a strong but incomplete concordance between tachykinin and medium-sized spiny neuronal phenotypes, because a minor variant of medium-sized spiny neurons and rare subgroups of medium- and large-sized sparse spiny neurons also show the tachykinin neuromodulator signature. Taken together, these results suggest that neostriatal neurons show an early commitment to heterogeneous tachykinin phenotypes, although the full and final expression of their somatodendritic characteristics coincides with synaptogenesis

Using the Morris Water Maze to Assess Spatial Learning and Memory in Weanling Mice

Mouse models have been indispensable for elucidating normal and pathological processes that influence learning and memory. A widely used method for assessing these cognitive processes in mice is the Morris water maze, a classic test for examining spatial learning and memory. However, Morris water maze studies with mice have principally been performed using adult animals, which preclude studies of critical neurodevelopmental periods when the cellular and molecular substrates of learning and memory are formed. While weanling rats have been successfully trained in the Morris water maze, there have been few attempts to test weanling mice in this behavioral paradigm even though mice offer significant experimental advantages because of the availability of many genetically modified strains. Here, we present experimental evidence that weanling mice can be trained in the Morris water maze beginning on postnatal day 24. Maze-trained weanling mice exhibit significant improvements in spatial learning over the training period and results of the probe trial indicate the development of spatial memory. There were no sex differences in the animals' performance in these tasks. In addition, molecular biomarkers of synaptic plasticity are upregulated in maze-trained mice at the transcript level. These findings demonstrate that the Morris water maze can be used to assess spatial learning and memory in weanling mice, providing a potentially powerful experimental approach for examining the influence of genes, environmental factors and their interactions on the development of learning and memory

Biomarkers Improve Clinical Outcome Predictors of Mortality Following Non-Penetrating Severe Traumatic Brain Injury

This study assessed whether early levels of biomarkers measured in CSF within 24-h of severe TBI would improve the clinical prediction of 6-months mortality. This prospective study conducted at two Level 1 Trauma Centers enrolled adults with severe TBI (GCS a parts per thousand currency sign8) requiring a ventriculostomy as well as control subjects. Ventricular CSF was sampled within 24-h of injury and analyzed for seven candidate biomarkers (UCH-L1, MAP-2, SBDP150, SBDP145, SBDP120, MBP, and S100B). The International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) scores (Core, Extended, and Lab) were calculated for each patient to determine risk of 6-months mortality. The IMPACT models and biomarkers were assessed alone and in combination. There were 152 patients enrolled, 131 TBI patients and 21 control patients. Thirty six (27 %) patients did not survive to 6 months. Biomarkers were all significantly elevated in TBI versus controls (p < 0.001). Peak levels of UCH-L1, SBDP145, MAP-2, and MBP were significantly higher in non-survivors (p < 0.05). Of the seven biomarkers measured at 12-h post-injury MAP-2 (p = 0.004), UCH-L1 (p = 0.024), and MBP (p = 0.037) had significant unadjusted hazard ratios. Of the seven biomarkers measured at the earliest time within 24-h, MAP-2 (p = 0.002), UCH-L1 (p = 0.016), MBP (p = 0.021), and SBDP145 (0.029) had the most significant elevations. When the IMPACT Extended Model was combined with the biomarkers, MAP-2 contributed most significantly to the survival models with sensitivities of 97-100 %. These data suggest that early levels of MAP-2 in combination with clinical data provide enhanced prognostic capabilities for mortality at 6 months