Laboratoire de Neurosciences Cognitives et Adaptatives

The present study aimed to translate and validate the French version of the Pain Resilience Scale (PRS) that was initially created and validated within English-speaking populations. A total of 137 participants experiencing chronic pain completed the French version of the PRS and other questionnaires commonly used to evaluate resilience or vulnerability towards pain. Of these, 71 participants successfully retook the PRS measure within 15 days of their initial participation. A principal component analysis was employed to evaluate the internal structure of the questionnaire. Following classical test theory, internal consistency, convergent validity, and test-retest reliability were checked for the chosen model. Lastly, an item response theory analysis (IRT) was conducted for the 2 PRS dimensions. Factor analyses identified a two-factor solution consistent to the original English version of the PRS. The findings demonstrated that the scale's internal consistency and test-retest reliability meet the requirements for classical psychometric qualities. The overall PRS score and its subscales showed good convergent validity with measures assessing resilience or vulnerability processes to pain. IRT results highlighted difficulties with some items on each of the 2 dimensions that complement the results of the previous classical analyses. The French version of the PRS scale is a reliable tool for measuring pain-specific resilience toward persistent pain.

The hippocampus is an essential brain structure for memory and emotional regulation and is particularly vulnerable to early life stress, which disrupts its development and increases the risk of neuropsychiatric disorders. Using the neonatal maternal separation model of early life stress, we explored sex-specific behavioral and molecular alterations, focusing on hippocampal function, neuroinflammation, and associated signaling pathways. Our results show that neonatal maternal separation induces mechanical and thermal hypersensitivity, as well as anxiety-like behaviors in both male and female rats, but spatial memory deficits were observed exclusively in males. These male-specific cognitive impairments are associated with a pro-inflammatory response in the dorsal CA1 subregion of the hippocampus. Molecular analyses also showed sex- and region-specific changes in oxytocinergic signaling and chloride cotransporters, suggesting plastic mechanisms affecting local neuronal inhibition. These findings highlight the pronounced sex differences in hippocampal vulnerability to early adversity, with males displaying an intense neuroinflammatory signature in dorsal CA1 associated with spatial memory deficits. This work highlights that the cognitive component of pain needs to be studied more systematically to better understand sex differences that are not necessarily easy to observe in the sensory and emotional components.

Visual gamma entrainment using sensory stimuli (vGENUS) is a promising non-invasive therapeutic approach for Alzheimer's disease (AD), showing efficacy in improving memory function. However, its mechanisms of action remain poorly understood. Using young AppNL-F/MAPT double knock-in (dKI) mice, a model of early AD, we examined brain dynamics alterations before amyloid plaque onset. High-density EEG recordings and metrics from fields outside neuroscience were used to assess brain dynamics fluidity-a measure of the brain's ability to transition between activity states. We revealed that dKI mice exhibit early, awake state-specific reductions in brain dynamics fluidity associated with cognitive deficits in complex memory tasks. Daily vGENUS sessions over 2 weeks restored brain dynamics fluidity and rescued memory deficits in dKI mice. Importantly, these effects built up during the stimulation protocol and persisted after stimulation ended, suggesting long-term modulation of brain function. Based on these results, we propose a "brain dynamics repair" mechanism for vGENUS that goes beyond current amyloid-centric hypotheses. This dual insight-that brain dynamics are both a target for repair and a potential diagnostic tool-provides new perspectives on early Alzheimer's disease pathophysiology.

Pain and its management have been a predominant issue since the dawn of humanity. Pain has been the subject of much controversy and has constantly evolved across societies. The objective of this review is to trace the historical evolution of the concept of pain through the ages and to attempt to understand how modern theories of pain represent a legacy of ancestral knowledge passed down from culture to culture. We conducted a comprehensive review of primary and secondary sources across 6 major historical periods, including Pre-history, Antiquity, the Middle Ages, the Renaissance, the Modern, and Contemporary eras, using academic databases, specialized libraries, and historical archives. Results shows that during ancient civilizations, the understanding of pain oscillated between religious beliefs and medical advances. Antiquity societies made significant contributions to the understanding of pain mechanisms and management. Contrary to popular belief, significant advances were made during the Middle Ages despite the important impact of religion on the era's conceptualization of pain. During the Renaissance, the influence of religion waned, and secular medicine made significant progress. The development of pain theories peaked in the 19th century with technological advances. Long considered an expression of internal suffering, pain has fascinated humanity throughout history. The way pain has been perceived, understood, and treated has changed greatly over the centuries. This historical scientific review allows us to keep in mind that the vision we have of pain in Western society is predominantly based on the concrete heritage of ancient civilizations.

Mass spectrometry has become central to identifying and quantifying histone post-translational modifications (PTMs), surpassing limitations of antibody-based methods. Histones are dynamically modified by multiple structures, especially at lysine residues on their N-terminal tails, to regulate DNA-templated processes. Reliable identification of histone PTMs remains challenging and still requires manual curation. This study focused on the Lys27-Arg40 stretch of histone H3, considered four sequence variants, an increasing number of lysine PTMs and artifacts coming from histone sample processing, which resulted in many isobaric peptides. Our analysis revealed the value of low-mass b1 and cyclic immonium fragment ions to validate identification of the distinct peptidoforms. We examined how MS/MS spectra are transformed by common identification software during the conversion of raw files into peak lists, and highlighted how some parameters may erase the informative low-mass fragments. We targeted the detection of 40 H3 K27-R40 variant × PTM combinations, including the mouse-specific variants H3mm7 and H3mm13, in histone samples extracted from mouse testis and brain via a parallel reaction monitoring analysis. We only detected very low levels of unmodified H3mm7. Our work contributes to reliably deciphering the histone code shaped by distinct sequence variants and numerous combinations of PTMs.

Individual protoplasmic astrocytes have very complex and diverse spongiform shapes. The morphological diversity of astrocytes is determined by the structural and functional interactions of the astrocyte with its microenvironment. When faced with pathological conditions, astrocytes reorganize their morphology. Yet, little is known about the astrocytic response in pure tauopathies and its evolution over time. Here, we aimed to investigate the consequences of a primary neuronal tau pathology on astrocyte fine morphology at three stages of the disease using the transgenic Thy-Tau22 mouse model. We first showed that hippocampal astrocytes in Thy-Tau22 mice progressively accumulate hyperphosphorylated tau with age. We then developed a pipeline of analyses, including 3D reconstruction of hippocampal tdTomato-labeled astrocytes via a PHP.eB adeno-associated virus, confocal microscopy, Imaris software morphometric analysis, and an advanced statistical analysis. During normal aging, the complexity of astrocyte morphology peaked at adulthood, then declined. In contrast, in Thy-Tau22 mice, tauopathy was associated with a simpler initial morphology, followed by the appearance of a cluster of complex cells at the most advanced stage. Using principal component analysis and hierarchical clustering based on 10 morphological features, we were able to identify different astrocyte morphotypes whose relative proportion varies differently with age between WT and Thy-Tau22 mice. Interestingly, we revealed that a fraction of astrocytes with a complex morphology re-emerges late in tauopathy-affected animals. Our data highlight the concept of significant and reversible structural plasticity of astrocytes when faced with chronic pathological conditions.

Binge eating disorder (BED) is characterized by the rapid overconsumption of palatable food in a short amount of time, often leading to obesity. The endocannabinoid system (ECS), a system involved in palatable food intake, is highly expressed in reward-related brain regions and is involved in both obesity and BED. This study investigated differences in ECS expression between these conditions using male Wistar rats exposed to specific regimen over six weeks: a non-access group (NA) with a standard diet, a continuous access group (CA) with free-choice high-fat high-sugar (fcHFHS) diet modeling obesity, and an intermittent access group (IA) with intermittent fcHFHS access modeling BED. Food intake was measured, and brain tissues from the nucleus accumbens (NAc), dorsal striatum (DS), ventral tegmental area (VTA), and rostromedial tegmental nucleus (RMTg) were analyzed for ECS expression using qPCR and mass spectrometry. We identified differential ECS expression across palatable food access groups, with variations depending on the brain region (striatal or mesencephalic). Correlation analyses revealed ECS dysregulations dependent on the type (fat or sucrose) and quantity of palatable food consumed. Comparative network analysis revealed co-regulation patterns of ECS-related genes with specific signatures associated with each eating pattern, highlighting RMTg as a key region for future research in eating behavior.

ObjectivesMeasurement of serum neurofilament light chain (sNfL) protein is becoming a key biomarker for many neurological diseases. Several immunoassays have been developed to meet these clinical needs, revealing significant differences in terms of variability and results. Here, we propose a French multicenter comparison of 5 sNfL assays. Methods6 replicates of 3 pools with low (10 pg/mL), medium (30 pg/mL) and high (100 pg/mL) sNfL values and one replicate of 12 samples with growing sNfL values were analyzed by six independent French clinical laboratories. The analytical performances of the sNfL blood assay (Fujirebio®) on Lumipulse G were first evaluated then compared to four other immunoassays: NF-light V2 (Quanterix®) on SiMOA HD-X, Human NF-L (Biotechne®) on Ella, R-Plex Human Neurofilament L (MSD®) on Sector 2400; manual ELISA test using Uman Diagnostic/Quanterix®. ResultsInter-center comparison of the Lumipulse blood assay revealed limited but significant differences in the mean sNfL values across low, medium, and high pools between each city (p < 0.001) and between the two different batches used. Coefficients of variation of pools ranged from 2.0 to 16.9 %. Z-score of sNfL results of the 12 samples ranged from −1.70 to +1.71. Inter-technique comparison showed a systematic difference of sNfL values, with a overestimation of MSD and Ella over other tests. Nonetheless, results were all significantly correlated (p < 0.001). ConclusionThe automated Lumipulse assay produced comparable sNfL values across laboratories; but further adjustments are needed to harmonize sNfL results. Biologists and physicians should be aware of the variability in results between different immunoassay suppliers.

Please confirm that an ethics committee approval has been applied for or granted: Yes: I’m uploading the Ethics Committee Approval as a PDF file with this abstract submissionBackground and AimsTherapeutic virtual reality (VR) can alleviate pain and anxiety (Colloca 2020, Terzulli 2022, Terzulli 2023). This study aimed to assess VR hypnosis (VRH) on pain and anxiety during heat stimulation in healthy volunteers.MethodsFrench ethic committee approved the study on 04/02/2020. After written consent obtention, heat nociceptive stimulations (45°C/25s, 46°C/20s and 47°C/10s) were applied to the wrist of 22 healthy volunteers with a contact probe (QST.Lab, Strasbourg, France). The control period (without VRH, CTRL) was compared with the VRH period (HypnoVR Biofeedback®, VRH). Data on demographics, anxiety (STAI-trait/80), suggestibility (Stanford/12), pain intensity (Visual analog scale VASi/10), unpleasantness (VASu/10), and state anxiety (STAI-State/80) before CTRL (State 1), between CTRL and VRH (State 2) and after VRH (State 3), were collected.ResultsSignificant reductions were observed in VASi (4.7 ± 2.3 vs. 3.8/10 ± 2.5, p=0.002), VASu (5.3 ± 1.9 vs. 3.7/10 ± 2.5; p < 0.001), and anxiety State 3 vs. State 2 (26.6/80 ± 9.9 vs. 31.7 ± 10.9; p < 0.001), whereas not between State 1 and 2 (p>.05). Responders to VRH (i.e., decreased pain intensity > 10%, non-responders as those with no change (-10 to +10%), and inverse responders as those with an increase > 10%. For intensity, proportions were 59%, 32%, and 9%, respectively. For unpleasantness, proportions were 77%, 14%, and 9%, respectively. EP165 Table 1 EP165 Figure 1ConclusionsHypnoVR Biofeedback® reduced pain intensity, unpleasantness, and anxiety during heat stimuli. However, 9% of volunteers responded negatively, it is comparable with our previous study2. Further studies on patients are needed to correctly characterize these patients.

Huntington’s disease (HD) is a rare genetic neurodegenerative disorder which generally manifests in mid-adulthood and primary affects the striatum, leading to the development of cognitive, motor and neuropsychiatric symptoms. It is due to a CAG expansion in exon 1 of the HTT gene, and leads to various dysfunctions. We recently showed that HD striatal neurons undergo accelerated epigenetic aging characterized by a loss of epigenetic information, i.e. a decrease in the expression of striatal identity genes (e.g. Pde10a) and a re-expression of developmental genes (e.g. Onecut1). Although there is currently no cure available, various studies have demonstrated the beneficial effect of environmental enrichment (EE) in patients and animal models of HD. Using enrichment cages, we demonstrate a beneficial effect on cognition and other behavioral components, such as anxiety or apathy-like behaviour, in HD R6/1 transgenic mice. In order to characterize the underlying molecular mechanism, using OMICS techniques, we focus on the impact of EE housing on epigenetic and transcriptional regulations. Interestingly, our striatal RNAseq data generated from R6/1 mice show that EE housing induces an upregulation of genes linked to the adiponectin pathway (e.g. AdipoR2, adiponectin receptor 2), and partially normalizes the expression of developmental genes. This analysis is paralleled by CUT&Tag data, where we focus on neuronal H3K9 and H3K27 acetylation levels known to be deregulated in the disease, in order to specify the role of epigenetic regulations in this effect. Further analysis will enable us to identify which pathways respond positively to EE housing, potentially uncovering new therapeutic targets.