Neuroscience
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Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder involving abdominal pain and bowel dysfunction. IBS pain symptoms have been hypothesized to depend on peripheral and central mechanisms, but the pathophysiology is still unclear. The aim of the present study was to assess the contribution of cerebral and cerebrospinal processes to pain inhibition deficits in IBS. ⋯ Interestingly, across all subjects, counter-irritation analgesia was positively correlated with RIII-reflex inhibition (r=0.39, P=0.04) and negatively with pain-related anxiety (r=-0.61, P<0.001). In addition, individual differences in counter-irritation analgesia were predicted independently by the modulation of RIII responses (P=0.03) and by pain catastrophizing (P=0.01), with the latter mediating the effect of pain-related anxiety. In conclusion, these results demonstrate that pain inhibition deficits in female IBS-D patients depend on two potentially separable mechanisms reflecting: (1) altered descending modulation and (2) higher-order brain processes underlying regulation of pain and affect.
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Compelling lines of evidence indicate that overexpression of dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) in subjects with trisomy 21 (Down syndrome[DS]) contributes to the abnormal structure and function of the DS brain. In the present study, we used a novel, phospho-dependent antibody recognizing DYRK1A only with nonphosphorylated tyrosine 145 and 147 (DYRK1A Tyr-145/147P(-)), to investigate the expression pattern of this DYRK1A species in trisomic and disomic human and mouse brains. ⋯ In addition, DYRK1A Tyr-145/147P(-) was enriched in the nuclei of neuronal progenitors and newly born neurons in the adult hippocampal proliferative zone and also occurred in some cholinergic axonal terminals. Our data show a distinctive expression pattern of DYRK1A forms nonphosphorylated at Tyr-145 and Tyr-147 in the brain tissue and suggest that DS subjects may exhibit not only upregulation of total DYRK1A, but also more subtle differences in phosphorylation levels of this kinase in comparison with control individuals.
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The Jenna mutant mouse harbours an S140G mutation in Tuba1a that impairs tubulin heterodimer formation resulting in defective neuronal migration during development. The consequence of decreased neuronal motility is a fractured pyramidal cell layer in the hippocampus and wave-like perturbations in the cerebral cortex. Here, we extend our characterisation of this mouse investigating the laminar architecture of the superior colliculus (SC). ⋯ A quantitative assessment of neuronal number in adulthood reveals a massive reduction in postmitotic neurons in mutant animals, which we attribute to increased apoptotic cell death. Consistent with the role of the SC in modulating sensorimotor gating, and the circuitry that modulates this behaviour, we find that Jenna mutants exhibit an exaggerated acoustic startle response. Our results highlight the importance of Tuba1a for correct neuronal migration and implicate postnatal apoptotic cell death in the pathophysiological mechanisms underlying the tubulinopathies.
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A significant proportion of patients with Parkinson's disease suffers from digestive symptoms. Bilateral deep brain stimulation of the subthalamic nucleus has become a reliable therapeutic option for parkinsonian patients, but its effects on digestive motility remain poorly investigated. The aim of our study was to assess whether subthalamic stimulation could induce changes in gastric, colonic, and rectal motility and modulate brain centers involved in gut motility. ⋯ Unilateral subthalamic stimulation impacts on gut motility in anesthetized rats with a significant increase in colonic motility probably via the modulation of several brain centers. These findings warrant further confirmation in parkinsonian rat models before being transposed to clinical conditions.