Publications by authors named "Jean-Jacques Benoliel"

Article Synopsis
  • * The relationship between stress and epilepsy is supported by neurobiological mechanisms, such as HPA axis dysfunction and altered neuroplasticity, that link the two conditions.
  • * Future treatment approaches may involve collaboration between clinicians and scientists to develop personalized therapies, using data integration and advancements in machine learning and neuromodulation.
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  • The study investigated the role of brain-derived neurotrophic factor (BDNF) in epilepsy, specifically looking at its potential as a biomarker for epilepsy severity and related psychiatric conditions.
  • It analyzed serum BDNF levels in epilepsy patients from four centers in France, while documenting various clinical characteristics and conducting psychiatric screenings.
  • The results showed no significant correlation between serum BDNF levels and epilepsy features or depression, but found that the presence of anti-seizure medications (ASM) was linked to increased BDNF, especially with valproate and perampanel.
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  • - Stress can lead to depression, but individual vulnerability before stressful events plays a key role in how severely someone might be affected.
  • - Researchers studied rats' sleep patterns before and after a stress event (social defeat) to identify specific sleep stages linked to vulnerability to depression using electroencephalogram recordings.
  • - The study found early and late sleep biomarkers that can predict which rats are likely to become depressed, suggesting potential for developing treatments aimed at those at high risk of stress-induced depression.
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(1) Background: While a number of studies among military personnel focus on specific pathologies such as post-traumatic stress disorder (PTSD), anxiety, and depression, they do not address the cumulative impact on mental health of stressors related to the profession. The present study aims to determine the relationship between allostatic load and mental health status in a cohort of fit-for-duty soldiers prior to their deployment to Afghanistan. The aim is to better-define the consequences of stressor adjustment.

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  • The study investigated the antiseizure properties of Anacyclus pyrethrum (AEAPR), a plant used in traditional medicine for epilepsy treatment, particularly in conditions of oxidative stress, such as social isolation.
  • Using a pilocarpine model with socially isolated rats, researchers divided rats into treated (with AEAPR) and untreated groups, measuring their seizure activity and oxidative stress markers over time.
  • Results showed that AEAPR significantly reduced seizure frequency, duration, and severity, while also lowering oxidative stress indicators, suggesting it has potential as an effective treatment for epilepsy even in adverse conditions.
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Stress reactivity is a complex phenomenon associated with multiple and multimodal expressions and functions. Herein, we hypothesized that compared with healthy controls (HCs), adolescents with borderline personality disorder (BPD) would exhibit a stronger response to stressors and a deficit in self-perception of stress due to their lack of insight. Twenty adolescents with BPD and 20 matched HCs performed a socially evaluated mental arithmetic test to induce stress.

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The high neutrophil to lymphocyte ratio observed in critically ill patients with COVID-19 is associated with excessive levels of reactive oxygen species (ROS), which promote a cascade of biological events that drive pathological host responses. ROS induce tissue damage, thrombosis and red blood cell dysfunction, which contribute to COVID-19 disease severity. We suggest that free radical scavengers could be beneficial for the most vulnerable patients.

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After social stress, rats become vulnerable to depression, and this state is characterized by persistent low blood levels of brain-derived neurotrophic factor (BDNF). The aim of this study was to determine whether low BDNF levels are associated with long term autonomic changes. Defeated animals were subjected to four daily episodes of social defeats.

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Article Synopsis
  • The study examines how unresolved stress from past events can increase vulnerability to epilepsy and related conditions, using an experimental model involving social defeat in rats.
  • Researchers induced epilepsy in rats through kainic acid injections after social defeat and treated some with the antioxidant Tempol, discovering that Tempol reduced seizure frequency and prevented cognitive deficits and depression-like symptoms.
  • Findings suggest that antioxidant treatment after the onset of epilepsy may be effective in modifying the disease and preventing comorbidities in individuals affected by prior stressful experiences.
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  • Recent studies on chronic EEG (electroencephalogram) in humans and rats reveal that epilepsy exhibits cyclical patterns, with rhythms occurring on circadian (daily), multi-day, and even seasonal scales.
  • Analysis of over 30 days of EEG data in male epileptic rats showed distinct patterns of interictal epileptiform activity, specifically 2-3 day and 5-7 day rhythms.
  • Seizures tended to cluster during certain phases of these rhythms, indicating that there are specific times when the risk of seizures is higher, but these patterns were inconsistent across different animals and with human interventions.
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Major depressive disorder (MDD) in children and adolescents is a recurrent and disabling condition globally but its pathophysiology remains poorly elucidated and there are limited effective treatments available. We performed metabolic profiling of plasma samples based on ultra-high-performance liquid chromatography equipped with quadrupole time-offlight mass spectrometry to explore the potential biomarkers of depression in children and adolescents with MDD. We identified several perturbed pathways, including fatty acid metabolism-particularly the polyunsaturated fatty acids metabolism, and purine metabolism-that were associated with MDD in these young patients.

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After an intense and repeated stress some rats become vulnerable to depression. This state is characterized by persistent low serum BDNF concentration. Our objective was to determine whether electrophysiological markers can sign vulnerability to depression.

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Background: Mindfulness-based interventions for healthy behaviors such as exercise and dietary modifications have aroused growing interest. This study aims to test the effectiveness of a mindfulness-based intervention for the reduction of impulsive eating and the improvement of motivation to exercise among obese individuals.

Methods: One-hundred and twenty obese outpatients, aged 18 to 65years, diagnosed with a binge eating disorder, will be randomly assigned to one of the three following groups: mindfulness practice, sham meditation, or treatment as usual control.

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Repeated social defeat in the rat induces long-lasting cardiovascular changes associated with anxiety. In this study, we investigated the effects of repeated social defeat on breathing. Respiratory rate was extracted from the respiratory sinus arrhythmia (RSA) peak frequency of the ECG in rats subjected to social defeat for 4 consecutive days.

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Article Synopsis
  • Accumulation of stressful experiences can increase the risk of developing epilepsy and related issues, but it's uncertain if this vulnerability can be anticipated or undone.
  • A study on rats showed that social defeat didn't cause depression on its own, but it did lower the threshold for seizures and led to cognitive and mood problems after epilepsy developed in 50% of cases.
  • Low levels of brain-derived neurotrophic factor (BDNF) before seizures helped identify vulnerable individuals, and administering a BDNF analog before seizures could prevent these additional problems from occurring.
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Anxiety disorders in humans reduce both the heart rate variability (HRV) and the sensitivity of the cardiac baroreflex (BRS). Both may contribute to sudden death. To elucidate the mechanisms underlying these alterations, male rats were subjected to social defeat sessions on four consecutive days.

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Article Synopsis
  • * After a stress event, while normal hormone levels returned in all animals, only 58% showed full recovery in other biological measures, indicating a subgroup (nonvulnerable) that remained unaffected.
  • * The remaining 42% (vulnerable group) exhibited persistent changes linked to depression, and a specific treatment helped mitigate these depressive symptoms, highlighting BDNF levels as a potential biomarker for depression risk.
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Defence responses triggered experimentally in rats by stimulation of the dorsomedial nucleus of the hypothalamus (DMH) and the dorsolateral periaqueductal grey matter (PAG) inhibit the cardiac baroreflex response (i.e. bradycardia).

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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.

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Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor κB (NF-κB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor.

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Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor.

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Background: Aldosterone, the final mediator of the renin-angiotensin-aldosterone pathway, is at its highest plasma levels at presentation for ST-elevation myocardial infarction (STEMI). Whether aldosterone level at presentation for STEMI is associated with adverse outcome remains unknown.

Methods And Results: Plasma aldosterone levels were measured at presentation in consecutive patients referred for primary percutaneous coronary intervention for STEMI.

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Keeping in mind the increased pain complaints reported in anxious or depressive patients, our goal was to investigate in rats the consequences of an experimentally provoked state of anxiety/depression on pain behavior and on its underlying mechanisms. We therefore used a model of social defeat consisting of a 30 min protected confrontation followed by a 15 min physical confrontation, repeated during 4 d, that elicited symptoms close to those observed in humans with anxiety or depression. Indeed, 5 d later, animals subjected to social-defeat confrontation were characterized by a decrease of sweet-water consumption and of body weight, and a hyperactivity of the hypothalamic-pituitary-adrenal axis, suggesting that the social-defeat procedure induced a prolonged state of anxiety.

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The involvement of cholecystokinin (CCK) in the potential anxiolytic-like effects of melatonin and of the antitumor MT(1/2) receptor agonist, S23478, was assessed by measuring the cortical outflow of CCK-like material (CCKLM) in a rat model of anticipation of social defeat. After repeated social defeats by a male Tryon Maze Dull (TMD) rat, Sprague-Dawley (SD) rats were implanted for microdialysis in the frontal cortex and placed in the same environment as for the defeated sessions, but no confrontation with the TMD rat was allowed. Anticipation of social defeat induced anxiety-like behaviors (immobility, ultrasonic vocalization, defensive postures) associated with a significant increase (approximately +90%) in cortical CCKLM outflow in SD rats.

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