Semantic context-processing deficit in thought-disordered schizophrenic patients: Evidence from new semantic priming paradigms

Introduction. Disorders in the processing of the semantic context are now a well-established phenomenon in thought-disordered (TD) schizophrenic patients, and have been revealed especially well by studies that have made use of the experimental paradigm of lexical decision tasks coupled with semantic priming. The main question addressed by this study was the evaluation of the experimental conditions under which TD schizophrenic patients are able to deploy cognitive strategies for semantic context processing. Methods. We studied semantic priming in two double lexical decision tasks (i.e., involving the explicit processing of the prime word) using a sequential presentation of words (stimulus onset asynchrony; SOA 500?ms) with a different proportion of related words (Experiment 1 with 25% vs. Experiment 2 with 15%) in 15 TD schizophrenic and 15 normal participants. Results. The results showed no significant differences between the semantic priming of TD schizophrenic and normal participants for Experiment 1, unlike Experiment 2 in which we observed a significant reduction of the amplitude of semantic priming in TD schizophrenic patients. The results of Experiment 1 contrast with those obtained previously (Besche et al., 1997) using a classical lexical decision task (implicit processing of the prime word) which also contained 25% related words. Conclusions. Experimental variables, such as the cognitive processing required by the prime word or the proportion of related words or the way they are manipulated, all seem to influence the emergence of semantic priming abnormalities in TD schizophrenic patients.     

Chronic stress induces transient spinal neuroinflammation,triggering sensory hypersensitivity and long-lasting anxiety-induced hyperalgesia

Chronic stressful events induce biochemical, physiological and psychological changes, resulting in stress-related neuropsychiatric disorders, such as anxiety or depression. Using repeated social defeat as a stressful event model, we show that this preclinical paradigm induces a transient increase in the expression of the genes encoding the pro-inflammatory molecules iNOS and COX-2. We provide the first demonstration that chronic stress affects spinal plasticity through a mechanism involving local neuroinflammation. The functional consequences of such neuroinflammation are associated with a transient decrease in the mechanical nociceptive threshold. Administration of the cholecystokinin(CCK)-2 receptor antagonist, CI-988, directly into the Rostral Ventromedial Medulla reverses the chronic stress-induced decrease in the nociceptive threshold. These data strongly suggest that chronic stress induces a spinal neuroinflammation associated with transient sensory hypersensitivity involving the activation of CCK-dependent nociceptive descending facilitatory pathways. Pharmacological data show that chronic social stress-induced long-lasting state of anxiety is not responsible for maintaining the spinal neuroinflammation and, therefore, for the associated sensory hypersensitivity. Conversely, an evaluation of pain-related behavior in the formalin model indicates that anxiety is directly related to prolonged hyperalgesia prevented by systemic benzodiazepine or CCK-2 receptor antagonist treatments. The present study highlights the adverse effects of chronic stress on spinal neuroinflammation triggering sensory hypersensitivity. Exploration of this phenomenon points out the divergence between pain sensitivity and anxiety-induced hyperalgesia, which is in agreement with clinical observations. Altogether, these data open up new perspectives for clinical research devoted to the evaluation and treatment of pain in anxio-depressive patients.     

Cowpox Virus Transmission from Pet Rats to Humans, France

In early 2009, four human cases of cowpox virus cutaneous infection in northern France, resulting from direct contact with infected pet rats (Rattus norvegicus), were studied. Pet rats, originating from the same pet store, were shown to be infected by a unique virus strain. Infection was then transmitted to humans who purchased or had contact with pet rats.     

Complementary actions of dopamine D2 receptor agonist and anti‐vegf therapy on tumoral vessel normalization in a transgenic mouse model

Angiogenesis contributes in multiple ways to disease progression in tumors and reduces treatment efficiency. Molecular therapies targeting Vegf signaling combined with chemotherapy or other drugs exhibit promising results to improve efficacy of treatment. Dopamine has been recently proposed to be a novel safe anti‐angiogenic drug that stabilizes abnormal blood vessels and increases therapeutic efficacy. Here, we aimed to identify a treatment to normalize tumoral vessels and restore normal blood perfusion in tumor tissue with a Vegf receptor inhibitor and/or a ligand of dopamine G protein‐coupled receptor D2 (D2R). Dopamine, via its action on D2R, is an endogenous effector of the pituitary gland, and we took advantage of this system to address this question. We have used a previously described Hmga2/T mouse model developing haemorrhagic prolactin‐secreting adenomas. In mutant mice, blood vessels are profoundly altered in tumors, and an aberrant arterial vascularization develops leading to the loss of dopamine supply. D2R agonist treatment blocks tumor growth, induces regression of the aberrant blood supply and normalizes blood vessels. A chronic treatment is able to restore the altered balance between pro‐ and anti‐angiogenic factors. Remarkably, an acute treatment induces an upregulation of the stabilizing factor Angiopoietin 1. An anti‐Vegf therapy is also effective to restrain tumor growth and improves vascular remodeling. Importantly, only the combination treatment suppresses intratumoral hemorrhage and restores blood vessel perfusion, suggesting that it might represent an attractive therapy targeting tumor vasculature. Similar strategies targeting other ligands of GPCRs involved in angiogenesis may identify novel therapeutic opportunities for cancer.     

Recessive MYPN mutations cause cap myopathy with occasional nemaline rods

Congenital myopathies are phenotypically and genetically heterogeneous. We describe homozygous truncating mutations in MYPN in 2 unrelated families with a slowly progressive congenital cap myopathy. MYPN encodes the Z‐line protein myopalladin implicated in sarcomere integrity. Functional experiments demonstrate that the mutations lead to mRNA defects and to a strong reduction in full‐length protein expression. Myopalladin signals accumulate in the caps together with alpha‐actinin. Dominant MYPN mutations were previously reported in cardiomyopathies. Our data uncover that mutations in MYPN cause either a cardiac or a congenital skeletal muscle disorder through different modes of inheritance. Ann Neurol 2017;81:467–473