Physical activity in patients with axial spondyloarthritis: a cross-sectional study of 203 patients

Physical activity is recommended in axial spondyloarthritis (axSpA) but may be insufficiently performed. The objective of this study was to assess physical activity in axial spondyloarthritis and to explore its explanatory factors. This was a cross-sectional study of patients with definite axSpA. The level of physical activity (International Physical Activity Questionnaire-Long form, IPAQ-L), type of aerobic exercise and the Exercise Benefits and Barriers Score were collected. Multivariate logistic regression analyses were performed to explain levels of exercise at least as recommended by the World Health Organization. In all, 203 patients were included: mean age 46.0 ± 11.6 years, 108 (53.2 %) males, mean Bath Ankylosing Spondylitis Activity Index (0–100) 37.8 ± 19.9; 137 (68.8 %) were treated with TNF-inhibitors. In all, 111 patients (54.7 %) were exercising at least as recommended; 96 (47.2 %) were in the ‘high physical activity’ category. Aerobic exercise >30 min was performed at least once a week by 61 (30.0 %) patients; the most frequent activities were energetic walking (31.0 %) and swimming (21.2 %). Main perceived benefits of exercising were improving physical fitness and functioning of the cardiovascular system, and the main barrier was physical exertion. Patients with paid employment had lower levels of physical activity whereas other demographic variables, disease activity/severity or TNF-inhibitor treatment were not predictive. One half of these patients performed enough physical activity according to the recommendations, similarly to the French population. Levels of physical activity did not appear to be explained by disease-related variables. Physical activity should be encouraged in axSpA.     

Dopamine neuronal responses in monkeys performing visually cued reward schedules

Dopamine neurons are important for reward-related behaviours. They have been recorded during classical conditioning and operant tasks with stochastic reward delivery. However, daily behaviour, although frequently complex in the number of steps, is often very predictable. We studied the responses of 75 dopamine neurons during schedules of trials in which the events and related reward contingencies could be well-predicted, within and across trials. In this visually cued reward schedule task, a visual cue tells the monkeys exactly how many trials, 1, 2, 3, or 4, must be performed to obtain a reward. The number of errors became larger as the number of trials remaining before the reward increased. Dopamine neurons frequently responded to the cues at the beginning and end of the schedules. Approximately 75% of the first-cue responsive neurons did not distinguish among the schedules that were beginning even though the cues were different. Approximately half of the last-cue responsive neurons depended on which schedule was ending, even though the cue signalling the last trial was the same in all schedules. Thus, the responses were related to what the monkey knew about the relation between the cues and the schedules, not the identity of the cues. These neurons also frequently responded to the go signal and/or to the OK signal indicating the end of a correctly performed trial whether a reward was forthcoming or not, and to the reward itself. Thus, dopamine neurons seem to respond to behaviourally important, i.e. salient, events even when the events have been well-predicted.     

Cellular parkin mutants are soluble under non-stress conditions

The parkin gene encodes an E3 ubiquitin ligase and loss of function mutations herein are the most frequent cause of early-onset Parkinson's disease. Reports have suggested that aggregation of mutant protein is the cause of the loss of function. We established stably transfected SH-SY5Y dopaminergic cell lines expressing wild-type and mutant parkin proteins. All the mutant proteins were soluble but could be rendered insoluble by subjecting the cellsto stress by proteasomal inhibition, treatment with oxidants and upon transient expression of the mutant proteins. A functional assay demonstrated that the R42P mutant retained functional activity in contrast to the W453stop mutant. Accordingly, the functional impairment by the mutations is not simply caused by turning the proteins insoluble.     

Soluble oligomers of amyloid-beta peptide induce neuronal apoptosis by activating a cPLA2-dependent sphingomyelinase-ceramide pathway

Recent data have revealed that soluble oligomeric amyloid-beta peptide (Abeta) may be the proximate effectors of neuronal injuries and death in Alzheimer's disease (AD) by unknown mechanisms. Consistently, we recently demonstrated the critical role of a redox-sensitive cytosolic calcium-dependent phospholipase A2 (cPLA2)-arachidonic acid (AA) pathway in Abeta oligomer-induced cell death. According to the involvement of oxidative stress and polyunsaturated fatty acids like AA in the regulation of sphingomyelinase (SMase) activity, the present study underlines the role of SMases in soluble Abeta-induced apoptosis. Soluble Abeta oligomers induced the activation of both neutral and acidic SMases, as demonstrated by the direct measurement of their enzymatic activities, by the inhibitory effects of both specific neutral and acidic SMase inhibitors, and by gene knockdown using antisense oligonucleotides. Furthermore, soluble Abeta-mediated activation of SMases and subsequent cell death were found to be inhibited by antioxidant molecules and a cPLA2-specific inhibitor or antisense oligonucleotide. We also demonstrate that sphingosine-1-phosphate is a potent neuroprotective factor against soluble Abeta oligomer-induced cell death and apoptosis by inhibiting soluble Abeta-induced activation of acidic sphingomyelinase. These results suggest that Abeta oligomers induce neuronal death by activating neutral and acidic SMases in a redox-sensitive cPLA2-AA pathway.     

'One night' sleep deprivation stimulates hippocampal neurogenesis

Neurogenesis in the adult hippocampus can be up- or downregulated in response to a variety of physiological and pathological conditions. Among these, dysregulation of hippocampal neurogenesis has been recently implicated in the pathogenesis of depression. In addition, in animal models of depression, a variety of antidepressant treatments reverse that condition by increasing neurogenesis. As one night sleep deprivation is known to improve mood in depressed patients for at least 1 day, we investigated whether a comparable treatment may affect hippocampal neurogenesis in adult rats. Accordingly, rats were sleep-deprived by gentle handling for 12 h during their physiological period of rest, and were injected with bromodeoxyuridine 4 h and 2 h before the end of sleep deprivation. They were then perfused immediately thereafter, or after 15 days and 30 days. We found that 12 h sleep deprivation significantly increased cell proliferation and the total number of surviving cells in the hippocampal dentate gyrus soon after sleep deprivation, as well as 15 days and 30 days later, in comparison to control rats allowed to sleep. No changes were instead found in the subventricular zone of the lateral ventricles, indicating that 12 h sleep deprivation selectively triggers neurogenic signals to the hippocampus. The present data include acute sleep deprivation among the conditions which upregulate hippocampal neurogenesis and raise the possibility that such response could be implicated in the beneficial effects elicited in depressed patients by one night sleep deprivation. Thus, the findings could contribute to the understanding of the intriguing relationship between depression and neurogenesis in the adult brain.     

Classical lissencephaly associated with dolichocephaly, hair and nail defect

We report on an 1-day-old boy with classical lissencephaly (grade 1, according to Kato and Dobyns, 2003) associated with an extended phenotype, including dolichocephaly, and hair and nail defects. The diagnosis of lissencephaly was made in utero, allowing the rapid characterization of the phenotype at birth. Because previously reported cases were not associated with the features described in our proband, they might represent a newly identified condition.