AGATHE: A tool for personalized rehabilitation of cognitive functions

Stroke, traumatic brain injury, multiple sclerosis, Parkinson's disease, Alzheimer's... Every year in France, tens of thousands of people fall victim to one of those neurological pathologies. Acquired brain injury leads to cognitive impairment and heavy loss of autonomy. Rehabilitation interventions are needed to enable people to recover capacity and return to Activities of Daily Living (ADL), such as grocery shopping. Unfortunately, the resources made available in cognitive rehabilitation are insufficient for the growing needs of victims of brain damage. The assets of virtual reality to address this big problem of public health are today scientifically recognized [Rizzo and Kim 2005; Klinger, et al. 2010]. In this context, we designed the AGATHE tool (Adaptable, configurable and upgradable tool for the generation of personalized therapeutic applications in cognitive rehabilitation) (AGATHE project, ANR-09-TECS-002).French National Research Agency (ANR) Laval Agglomération et Conseil Général de la Mayenn

Polyphenol-rich extract from grape and blueberry attenuates cognitive decline and improves neuronal function in aged mice

Ageing is characterised by memory deficits, associated with brain plasticity impairment. Polyphenols from berries, such as flavan-3-ols, anthocyanins, and resveratrol, have been suggested to modulate synaptic plasticity and cognitive processes. In the present study we assessed the preventive effect of a polyphenol-rich extract from grape and blueberry (PEGB), with high concentrations of flavonoids, on age-related cognitive decline in mice. Adult and aged (6 weeks and 16 months) mice were fed a PEGB-enriched diet for 14 weeks. Learning and memory were assessed using the novel object recognition and Morris water maze tasks. Brain polyphenol content was evaluated with ultra-high-performance LC-MS/MS. Hippocampal neurotrophin expression was measured using quantitative real-time PCR. Finally, the effect of PEGB on adult hippocampal neurogenesis was assessed by immunochemistry, counting the number of cells expressing doublecortin and the proportion of cells with dendritic prolongations. The combination of grape and blueberry polyphenols prevented age-induced learning and memory deficits. Moreover, it increased hippocampal nerve growth factor (Ngf) mRNA expression. Aged supplemented mice displayed a greater proportion of newly generated neurons with prolongations than control age-matched mice. Some of the polyphenols included in the extract were detected in the brain in the native form or as metabolites. Aged supplemented mice also displayed a better survival rate. These data suggest that PEGB may prevent age-induced cognitive decline. Possible mechanisms of action include a modulation of brain plasticity. Post-treatment detection of phenolic compounds in the brain suggests that polyphenols may act directly at the central level, while they can make an impact on mouse survival through a potential systemic effect

AGATHE: A tool for personalized rehabilitation of cognitive functions

Stroke, traumatic brain injury, multiple sclerosis, Parkinson's disease, Alzheimer's... Every year in France, tens of thousands of people fall victim to one of those neurological pathologies. Acquired brain injury leads to cognitive impairment and heavy loss of autonomy. Rehabilitation interventions are needed to enable people to recover capacity and return to Activities of Daily Living (ADL), such as grocery shopping. Unfortunately, the resources made available in cognitive rehabilitation are insufficient for the growing needs of victims of brain damage. The assets of virtual reality to address this big problem of public health are today scientifically recognized [Rizzo and Kim 2005; Klinger, et al. 2010]. In this context, we designed the AGATHE tool (Adaptable, configurable and upgradable tool for the generation of personalized therapeutic applications in cognitive rehabilitation) (AGATHE project, ANR-09-TECS-002).French National Research Agency (ANR) Laval Agglomération et Conseil Général de la Mayenn

Tye7 regulates yeast Ty1 retrotransposon sense and antisense transcription in response to adenylic nucleotides stress

Transposable elements play a fundamental role in genome evolution. It is proposed that their mobility, activated under stress, induces mutations that could confer advantages to the host organism. Transcription of the Ty1 LTR-retrotransposon of Saccharomyces cerevisiae is activated in response to a severe deficiency in adenylic nucleotides. Here, we show that Ty2 and Ty3 are also stimulated under these stress conditions, revealing the simultaneous activation of three active Ty retrotransposon families. We demonstrate that Ty1 activation in response to adenylic nucleotide depletion requires the DNA-binding transcription factor Tye7. Ty1 is transcribed in both sense and antisense directions. We identify three Tye7 potential binding sites in the region of Ty1 DNA sequence where antisense transcription starts. We show that Tye7 binds to Ty1 DNA and regulates Ty1 antisense transcription. Altogether, our data suggest that, in response to adenylic nucleotide reduction, TYE7 is induced and activates Ty1 mRNA transcription, possibly by controlling Ty1 antisense transcription. We also provide the first evidence that Ty1 antisense transcription can be regulated by environmental stress conditions, pointing to a new level of control of Ty1 activity by stress, as Ty1 antisense RNAs play an important role in regulating Ty1 mobility at both the transcriptional and post-transcriptional stages

Activation of MEK1 or MEK2 isoform is sufficient to fully transform intestinal epithelial cells and induce the formation of metastatic tumors

<p>Abstract</p> <p>Background</p> <p>The Ras-dependent ERK1/2 MAP kinase signaling pathway plays a central role in cell proliferation control and is frequently activated in human colorectal cancer. Small-molecule inhibitors of MEK1/MEK2 are therefore viewed as attractive drug candidates for the targeted therapy of this malignancy. However, the exact contribution of MEK1 and MEK2 to the pathogenesis of colorectal cancer remains to be established.</p> <p>Methods</p> <p>Wild type and constitutively active forms of MEK1 and MEK2 were ectopically expressed by retroviral gene transfer in the normal intestinal epithelial cell line IEC-6. We studied the impact of MEK1 and MEK2 activation on cellular morphology, cell proliferation, survival, migration, invasiveness, and tumorigenesis in mice. RNA interference was used to test the requirement for MEK1 and MEK2 function in maintaining the proliferation of human colorectal cancer cells.</p> <p>Results</p> <p>We found that expression of activated MEK1 or MEK2 is sufficient to morphologically transform intestinal epithelial cells, dysregulate cell proliferation and induce the formation of high-grade adenocarcinomas after orthotopic transplantation in mice. A large proportion of these intestinal tumors metastasize to the liver and lung. Mechanistically, activation of MEK1 or MEK2 up-regulates the expression of matrix metalloproteinases, promotes invasiveness and protects cells from undergoing anoikis. Importantly, we show that silencing of MEK2 expression completely suppresses the proliferation of human colon carcinoma cell lines, whereas inactivation of MEK1 has a much weaker effect.</p> <p>Conclusion</p> <p>MEK1 and MEK2 isoforms have similar transforming properties and are able to induce the formation of metastatic intestinal tumors in mice. Our results suggest that MEK2 plays a more important role than MEK1 in sustaining the proliferation of human colorectal cancer cells.</p

Dietary polyphenol supplementation prevents alterations of spatial navigation in middle-aged mice

Spatial learning and memory deficits associated with hippocampal synaptic plasticity impairments are commonly observed during aging. Besides, the beneficial role of dietary polyphenols has been suggested as potential functional food candidates to prevent this memory decline. Indeed, polyphenols could potentiate the signaling pathways of synaptic plasticity underlying learning and memory. In this study, spatial learning deficits of middle-aged mice were first highlighted and characterized according to their navigation patterns in the Morris water maze task. An eight-week polyphenol-enriched diet, containing a polyphenol-rich extract from grape and blueberry (PEGB; from the Neurophenols Consortium) with high contents of flavonoids, stilbenes and phenolic acids, was then successful in reversing these age-induced effects. The use of spatial strategies was indeed delayed with aging whereas a polyphenol supplementation could promote the occurrence of spatial strategies. These behavioral results were associated with neurobiological changes: while the expression of hippocampal calmodulin kinase II (CaMKII) mRNA levels was reduced in middle-aged animals, the polyphenol-enriched diet could rescue them. Besides, an increased expression of nerve growth neurotrophic factor (NGF) mRNA levels was also observed in supplemented adult and middle-aged mice. Thus these data suggest that supplementation with polyphenols could be an efficient nutritional way to prevent age-induced cognitive decline

Les personnes âgées adressées aux urgences pour problèmes de maintien à domicile. Entretiens auprès de médecins généralistes angevins

ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Beyond decision! Motor contribution to speed-accuracy trade-off in decision-making

International audienceBoth in real life and experimental settings, increasing response speed typically leads to more error-prone actions. Processes underlying such a " speed-accuracy trade-off " (SAT) are usually assumed to be purely decisional: cautiousness would be determined only by the amount of sensory evidence required to select a response. The present data challenges this largely accepted view, by directly showing that motor processes are speeded up under time pressure. In a choice reaction time task where emphasis was put either on response speed or accuracy, motor processes were investigated through the analysis of muscular activity related to response execution. When response speed was emphasized , the time between electromyographic onset and behavioral response (motor time) was also speeded up (contributing for more than 20 % of the total effect on global reaction time). This speeded execution (likely due to a more efficient motor command) may also explain why participants are less able to interrupt incorrect response execution once started (Burle et al 2014), leading to more overt errors. Pointing to a speed-accuracy exchange within motor processes themselves, the present results call for a re-evaluation of widely accepted assumptions about SAT, and more generally, decision-making processes. They are discussed in the context of recent extensions of the drift diffusion model framework, questioning the strict separation between decisional and motor processes

Efficacy of Seren@ctif, a Computer-Based Stress Management Program for Patients With Adjustment Disorder With Anxiety: Protocol for a Controlled Trial

BACKGROUND: Adjustment disorder with anxiety (ADA) is the most frequent and best characterized stress-related psychiatric disorder. The rationale for prescription of benzodiazepine monotherapy is a public health issue. Cognitive behavioral stress management programs have been studied in many countries. Several reports have shown beyond reasonable doubt their efficiency at reducing perceived stress and anxiety symptoms and improving patient quality of life. Considering the number of people who could benefit from such programs but are unable to access them, self-help programs have been offered. First presented as books, these programs became enriched with computer-based and digital supports. Regrettably, programs for stress management based on cognitive behavioral therapy (CBT), both face-to-face and digital support, have been only minimally evaluated in France. To our knowledge, the Seren@ctif program is the first French language self-help program for stress management using digital supports.OBJECTIVE: The aim of this study is to assess the effectiveness of a 5-week standardized stress management program for reducing anxiety conducted via eLearning (iCBT) or through face-to-face interviews (CBT) with patients suffering from ADA compared with a wait list control group (WLC). These patients seek treatment in a psychiatric unit for anxiety disorders at a university hospital. The primary outcome is change in the State Trait Anxiety Inventory scale trait subscale (STAI-T) between baseline and 2-month visit.METHODS: This is a multicenter, prospective, open label, randomized controlled study in 3 parallel groups with balanced randomization (1:1:1): computer-based stress management with minimal contact (not fully automated) (group 1), stress management with face-to-face interviews (group 2), and a WLC group that receives usual health care from a general practitioner (group 3). Programs are based on standard CBT principles and include 5 modules in 5 weekly sessions that include the following topics: stress and stress reaction and assessment; deep respiration and relaxation techniques; cognitive restructuring, mindfulness, and acceptance; behavioral skills as problem solving; and time management, healthy behaviors, and emotion regulation. In the Internet-based group, patients have minimal contact with a medical professional before and after every session. In the first session, a flash memory drive is supplied containing videos, audio files, a self-help book portfolio in the form of an eGuide, and log books providing the exercises to be completed between 2 sessions. The patient is encouraged to practice a 20-minute daily exercise 5 or 6 times per week. In the face-to-face group, patients receive the same program from a therapist with 5 weekly sessions without digital support. Interviews and self-assessments were collected face-to-face with the investigator.RESULTS: The feasibility of this program is being tested, and results show good accessibility in terms of acceptance, understanding, and treatment credibility. Results are expected in 2018.CONCLUSIONS: To our knowledge, this is the first French study to examine the effectiveness of a computer-based stress management program for patients with ADA. The Seren@ctif program may be useful within the framework of a psychoeducative approach. It could also be advised for people suffering from other diseases related to stress and for people with a clinical level of perceived stress. TRIAL REGISTRATION: Clinicaltrials.gov NCT02621775; https://clinicaltrials.gov/ct2/show/NCT02621775 (Archived by WebCite at http://www.webcitation.org/6tQrkPs1u)