Self-perceived physical level and fitness performance in children and adolescents with inflammatory bowel disease

Background: Inflammatory bowel disease (IBD) patients show a higher risk of developing metabolic and cardiovascular diseases due to the presence of systemic low-grade chronic inflammation. Exercise can improve cardiovascular fitness and modulate the inflammatory processes. We evaluated the physical activity (PA) level and the fitness performance of children and adolescents with IBD. Patients and methods: We considered 54 pediatric patients with IBD (14.6 ± 2.2; 22 M), including CD (n = 27) UC (n = 24) and IBD unclassified (n = 3), and 70 healthy children. In all children, the Physical Activity Questionnaire (PAQ-C) and the International Fitness Enjoyment Scale were self-reported and recorded. Results: PAQ-C showed significant difference in PA levels in patients with IBD compared to controls (p < 0.001). A decrease in general fitness (p = 0.003), cardiorespiratory fitness (p = 0.002), strength (p = 0.01), speed agility (p = 0.003), and flexibility (p = 0.01) were also detected between patients and controls. Speed agility was related to age (p = 0.02) and BMI z-score (p = 0.01), and flexibility to BMI z-score (p = 0.05). We noted a correlation between PA levels and physician global assessment (p = 0.021) and activity disease severity (p = 0.025). Conclusions: A poorer PA level and poor physical competence were found in patients with IBD compared to healthy children and adolescents. Monitored exercise could provide multiple benefits at both physical and psychological levels

Neurogenesis of medium spiny neurons in the nucleus accumbens continues into adulthood and is enhanced by pathological pain

In mammals, most adult neural stem cells (NSCs) are located in the ventricular–subventricular zone (V-SVZ) along the wall of the lateral ventricles and they are the source of olfactory bulb interneurons. Adult NSCs exhibit an apico-basal polarity; they harbor a short apical process and a long basal process, reminiscent of radial glia morphology. In the adult mouse brain, we detected extremely long radial glia-like fibers that originate from the anterior–ventral V-SVZ and that are directed to the ventral striatum. Interestingly, a fraction of adult V-SVZ-derived neuroblasts dispersed in close association with the radial glia-like fibers in the nucleus accumbens (NAc). Using several in vivo mouse models, we show that newborn neurons integrate into preexisting circuits in the NAc where they mature as medium spiny neurons (MSNs), i.e., a type of projection neurons formerly believed to be generated only during embryonic development. Moreover, we found that the number of newborn neurons in the NAc is dynamically regulated by persistent pain, suggesting that adult neurogenesis of MSNs is an experience-modulated process

HuD is a neural translation enhancer acting on mTORC1-responsive genes and counteracted by the Y3 small non-coding RNA

The RNA-binding protein HuD promotes neurogenesis and favors recovery from peripheral axon injury. HuD interacts with many mRNAs, altering both stability and translation efficiency. We generated a nucleotide resolution map of the HuD RNA interactome in motor neuron-like cells, identifying HuD target sites in 1,304 mRNAs, almost exclusively in the 3' UTR. HuD binds many mRNAs encoding mTORC1-responsive ribosomal proteins and translation factors. Altered HuD expression correlates with the translation efficiency of these mRNAs and overall protein synthesis, in a mTORC1-independent fashion. The predominant HuD target is the abundant, small non-coding RNA Y3, amounting to 70% of the HuD interaction signal. Y3 functions as a molecular sponge for HuD, dynamically limiting its recruitment to polysomes and its activity as a translation and neuron differentiation enhancer. These findings uncover an alternative route to the mTORC1 pathway for translational control in motor neurons that is tunable by a small non-coding RNA

L-type CaV1.2 deletion in the cochlea but not in the brainstem reduces noise vulnerability: implication for CaV1.2 mediated control of cochlear BDNF expression

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).-- et al.Voltage-gated L-type Ca2+ channels (L-VGCCs) like CaV1.2 are assumed to play a crucial role for controlling release of trophic peptides including brain-derived neurotrophic factor (BDNF). In the inner ear of the adult mouse, beside the well described L-VGCC CaV1.3, also CaV1.2 is expressed. Due to lethality of constitutive CaV1.2 KO mice, the function of this ion channel as well as its putative relationship to BDNF in the auditory system is entirely elusive. We recently described that BDNF plays a differential role for inner hair cell (IHC) vesicles release in normal and traumatized condition. To elucidate a presumptive role of CaV1.2 during this process, two tissue-specific conditional mouse lines were generated. To distinguish the impact of CaV1.2 on the cochlea from that on feedback loops from higher auditory centers CaV1.2 was deleted, in one mouse line, under the Pax2 promoter (CaV1.2Pax2) leading to a deletion in the spiral ganglion neurons (SGN), dorsal cochlear nucleus (DCN), and inferior colliculus (IC). In the second mouse line, the Egr2 promoter was used for deleting CaV1.2 (CaV1.2Egr2) in auditory brainstem nuclei. In both mouse lines normal hearing threshold and equal number of IHC release sites were observed. We found a slight reduction of auditory brainstem response (ABR) wave I amplitudes in the CaV1.2Pax2 mice but not in the CaV1.2Egr2 mice. After noise exposure, CaV1.2Pax2 mice had less pronounced hearing loss that correlated with maintenance of ribbons in IHCs and less reduced activity in auditory nerve fibers, as well as in higher brain centers at supra-threshold sound stimulation. As reduced cochlear BDNF mRNA levels were found in CaV1.2Pax2 mice, we suggest that a CaV1.2 dependent step may participate in triggering part of the beneficial and deteriorating effects of cochlear BDNF in intact systems and during noise exposure through a pathway that is independent of Cav1.2 function in efferent circuits. © 2013 Zuccotti, Lee, Campanelli, Singer, Satheesh, Patriarchi, Geisler, Köpschall, Rohbock, Nothwang, Hu, Hell, Schimmang, Rüttiger and Knipper.This work was supported by the Marie Curie Research Training Network CavNET MRTN-CT-2006-035367, the Deutsche Forschungsgemeinschaft DFG-Kni-316-4-1 and Hahn Stiftung (Index AG), and the NIHR 01AG017502. We acknowledge support by Deutsche Forschungsgemeinschaft and Open Access Publishing Fund of Tübingen University.Peer Reviewe

Lack of brain-derived neurotrophic factor hampers inner hair cell synapse physiology, but protects against noise-induced hearing loss

et al.The precision of sound information transmitted to the brain depends on the transfer characteristics of the inner hair cell (IHC) ribbon synapse and its multiple contacting auditory fibers. We found that brain derived neurotrophic factor (BDNF) differentially influences IHC characteristics in the intact and injured cochlea. Using conditional knock-out mice (BDNF Pax2 KO) we found that resting membrane potentials, membrane capacitance and resting linear leak conductance of adult BDNF Pax2 KO IHCs showed a normal maturation. Likewise, in BDNF Pax2 KO membrane capacitance (ΔC m) as a function of inward calcium current (I Ca) follows the linear relationship typical for normal adult IHCs. In contrast the maximal ΔC m, but not the maximal size of the calcium current, was significantly reduced by 45% in basal but not in apical cochlear turns in BDNF Pax2 KOIHCs. Maximal ΔC m correlated with a loss of IHC ribbons in these cochlear turns and a reduced activity of the auditory nerve (auditory brainstem response wave I). Remarkably, a noise-induced loss of IHC ribbons, followed by reduced activity of the auditory nerve and reduced centrally generated wave II and III observed in control mice, was prevented in equally noise-exposed BDNF Pax2 KO mice. Data suggest that BDNF expressed in the cochlea is essential for maintenance of adult IHC transmitter release sites and that BDNF upholds opposing afferents in high-frequency turns and scales them down following noise exposure. © 2012 the authors.This work was supported by the Marie Curie Research Training Network CavNET MRTN-CT-2006-035367, the Deutsche Forschungsgemeinschaft DFG-Kni-316-4-1 and Hahn Stiftung (Index AG), and by the Wellcome Trust, 088719 and 091895 (to W.M.). W.M. and S.L.J. are Royal Society University Research Fellows.Peer reviewe

Long term functionally requirement of BDNF for sound processing revealed by conditional gene deletion

Resumen del trabajo presentado al 37th MidWinter Meeting of the Association for Research in Otorhinolaryngology celebrado en San Diego (US) del 22 al 26 de febrero de 2014.-- et al.[Background]: The precision of sound information transmitted to the brain depends on the transfer characteristics of the inner hair cell (IHC) ribbon synapse and its multiple contacting auditory fibers. Discharge rate and synchronicity of auditory fibers define the amplitude of sound induced brainstem responses. [Methods]: We used two mouse lines with either a cell specific deletion of brain-derived nerve growth factor (BDNF) in the cochlea and parts of the brainstem and midbrain (BDNF Pax2) or with deletion of BDNF within the entire brain (BDNF TrkC). We looked for molecular and functional differences pre and post acoustic trauma.[Results]: We found that BDNF is essential for maintaining exocytosis in IHC synapses in high frequency cochlear turns as well as for maintaining proper targeting of associated afferent fibers within this region (Zuccotti et al Knipper 2012 J. Neurosci.). Comparison of this BDNF Pax2 mice with the BDNF TrkC mice revealed that IHC response characteristics pre and post acoustic trauma were triggered by BDNF in the cochlea and not by BDNF in the brain. [Conclusion]: Extracellular recording of neurons in the inferior colliculus in BDNF Pax2 mice were performed. A surprising novel role of BDNF dependent steps for sound-processing was unraveled.Peer reviewe

Noise-induced inner hair cell ribbon loss disturbs central arc mobilization: a novel molecular paradigm for understanding tinnitus

et al.Increasing evidence shows that hearing loss is a risk factor for tinnitus and hyperacusis. Although both often coincide, a causal relationship between tinnitus and hyperacusis has not been shown. Currently, tinnitus and hyperacusis are assumed to be caused by elevated responsiveness in subcortical circuits. We examined both the impact of different degrees of cochlear damage and the influence of stress priming on tinnitus induction. We used (1) a behavioral animal model for tinnitus designed to minimize stress, (2) ribbon synapses in inner hair cells (IHCs) as a measure for deafferentation, (3) the integrity of auditory brainstem responses (ABR) to detect differences in stimulus-evoked neuronal activity, (4) the expression of the activity-regulated cytoskeletal protein, Arc, to identify long-lasting changes in network activity within the basolateral amygdala (BLA), hippocampal CA1, and auditory cortex (AC), and (5) stress priming to investigate the influence of corticosteroid on trauma-induced brain responses. We observed that IHC ribbon loss (deafferentation) leads to tinnitus when ABR functions remain reduced and Arc is not mobilized in the hippocampal CA1 and AC. If, however, ABR waves are functionally restored and Arc is mobilized, tinnitus does not occur. Both central response patterns were found to be independent of a profound threshold loss and could be shifted by the corticosterone level at the time of trauma. We, therefore, discuss the findings in the context of a history of stress that can trigger either an adaptive or nonadaptive brain response following injury. © 2012 Springer Science+Business Media New York.This work was supported by the Marie Curie Research Training Network CavNET MRTN-CT-2006-035367, Deutsche Forschungsgemeinschaft DFG-Kni-316-4-1, and Hahn Stiftung (Index AG).Peer Reviewe

BDNF in lower brain parts modifies auditory fiber activity to gain fidelity but increases the risk for generation of central noise after injury

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.-- et al.For all sensory organs, the establishment of spatial and temporal cortical resolution is assumed to be initiated by the first sensory experience and a BDNF-dependent increase in intracortical inhibition. To address the potential of cortical BDNF for sound processing, we used mice with a conditional deletion of BDNF in which Cre expression was under the control of the Pax2 or TrkC promoter. BDNF deletion profiles between these mice differ in the organ of Corti (BDNF-KO) versus the auditory cortex and hippocampus (BDNF-KO). We demonstrate that BDNF-KO but not BDNF-KO mice exhibit reduced sound-evoked suprathreshold ABR waves at the level of the auditory nerve (wave I) and inferior colliculus (IC) (wave IV), indicating that BDNF in lower brain regions but not in the auditory cortex improves sound sensitivity during hearing onset. Extracellular recording of IC neurons of BDNF mutant mice revealed that the reduced sensitivity of auditory fibers in these mice went hand in hand with elevated thresholds, reduced dynamic range, prolonged latency, and increased inhibitory strength in IC neurons. Reduced parvalbumin-positive contacts were found in the ascending auditory circuit, including the auditory cortex and hippocampus of BDNF-KO, but not of BDNF-KO mice. Also, BDNF-WT but not BDNF-KO mice did lose basal inhibitory strength in IC neurons after acoustic trauma. These findings suggest that BDNF in the lower parts of the auditory system drives auditory fidelity along the entire ascending pathway up to the cortex by increasing inhibitory strength in behaviorally relevant frequency regions. Fidelity and inhibitory strength can be lost following auditory nerve injury leading to diminished sensory outcome and increased central noise.This work was supported by the Marie Curie Research Training Network CavNET MRTN-CT-2006-035367, the Deutsche Forschungsgemeinschaft DFG-Kni-316-4-1, and the Hahn Stiftung (Index AG).Peer Reviewe