Notch Signalling in the Hippocampus of Patients With Motor Neuron Disease

IntroductionThe Notch signalling pathway regulates neuronal survival. It has some similarities with the APP signalling pathway, and competes with the latter for α- and γ-secretase proteolytic complexes. The objective of this study was to study the Notch signalling pathway in the hippocampi of patients with motor neuron disease.MethodsWe studied biological material from the autopsies of 12 patients with motor neuron disease and 4 controls. We analysed the molecular markers of the Notch and APP signalling pathways, TDP43, tau, and markers of neurogenesis.Results and ConclusionLow NICD expression suggests Notch signalling pathway inactivation in neurons. Inactivation of the pathway despite increased Notch1 expression is associated with a lack of α-secretase expression. We observed increased β-secretase expression associated with activation of the amyloid cascade of APP, leading to increases in amyloid-β and AICD peptides and decreased levels of Fe65. Inactivation of the Notch signalling pathway is an important factor in decreased neurogenic response in the hippocampi of patients with amyotrophic lateral sclerosis

Biohybrids of scaffolding hyaluronic acid biomaterials plus adipose stem cells home local neural stem and endothelial cells: Implications for reconstruction of brain lesions after stroke.

[EN] Endogenous neurogenesis in stroke is insufficient to replace the lost brain tissue, largely due to the lack of a proper biological structure to let new cells dwell in the damaged area. We hypothesized that scaffolds made of hyaluronic acid (HA) biomaterials (BM) could provide a suitable environment to home not only new neurons, but also vessels, glia and neurofilaments. Further, the addition of exogenous cells, such as adipose stem cells (ASC) could increase this effect. Athymic mice were randomly assigned to a one of four group: stroke alone, stroke and implantation of BM, stroke and implantation of BM with ASC, and sham operated animals. Stroke model consisted of middle cerebral artery thrombosis with FeCl3. After 30 days, animals underwent magnetic resonance imaging (MRI) and were sacrificed. Proliferation and neurogenesis increased at the subventricular zone ipsilateral to the ventricle and neuroblasts, glial, and endothelial cells forming capillaries were seen inside the BM. Those effects increased when ASC were added, while there was less inflammatory reaction. Three-dimensional scaffolds made of HA are able to home newly formed neurons, glia, and endothelial cells permitting the growth neurofilaments inside them. The addition of ASC increase these effects and decrease the inflammatory reaction to the implant.Contract grant sponsor: CIBER BBN Contract grant sponsor: ERANET NEURON CALL; contract grant number: PRI-PIMNEU-2011-1372 Contract grant sponsor: Spanish Science & Innovation Ministery; contract grant number: MAT 2011-28791-C03-01, MAT 2011-28791-C03-02 an Contract grant sponsor: TERCEL; contract grant number: RD12/0019/0010 Contract grant sponsor: Spanish Ministry of Economy and Competitiveness through grants MAT2015-66666-C3, and DPI2015-72863-EXPSanchez-Rojas, L.; Gómez-Pinedo, U.; Benito-Martin, MS.; León-Espinosa, G.; Rascón-Ramirez, F.; Lendinez, C.; Martínez-Ramos, C.... (2019). 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FDG-PET-based neural correlates of Addenbrooke’s cognitive examination III scores in Alzheimer’s disease and frontotemporal degeneration

IntroductionThe Addenbrooke’s Cognitive Examination III (ACE-III) is a brief test useful for neuropsychological assessment. Several studies have validated the test for the diagnosis of Alzheimer’s disease (AD) and frontotemporal dementia (FTD). In this study, we aimed to examine the metabolic correlates associated with the performance of ACE-III in AD and behavioral variant FTD.MethodsWe enrolled 300 participants in a cross-sectional study, including 180 patients with AD, 60 with behavioral FTD (bvFTD), and 60 controls. An 18F-Fluorodeoxyglucose positron emission tomography study was performed in all cases. Correlation between the ACE-III and its domains (attention, memory, fluency, language, and visuospatial) with the brain metabolism was estimated.ResultsThe ACE-III showed distinct neural correlates in bvFTD and AD, effectively capturing the most relevant regions involved in these disorders. Neural correlates differed for each domain, especially in the case of bvFTD. Lower ACE-III scores were associated with more advanced stages in both disorders. The ACE-III exhibited high discrimination between bvFTD vs. HC, and between AD vs. HC. Additionally, it was sensitive to detect hypometabolism in brain regions associated with bvFTD and AD.ConclusionOur study contributes to the knowledge of the brain regions associated with ACE-III, thereby facilitating its interpretation, and highlighting its suitability for screening and monitoring. This study provides further validation of ACE-III in the context of AD and FTD

Sera from Patients with NMOSD Reduce the Differentiation Capacity of Precursor Cells in the Central Nervous System

Introduction: AQP4 (aquaporin-4)–immunoglobulin G (IgG)-mediated neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease that affects the central nervous system, particularly the spinal cord and optic nerve; remyelination capacity in neuromyelitis optica is yet to be determined, as is the role of AQP4–IgG in cell differentiation. Material and Methods: We included three groups—a group of patients with AQP4–IgG-positive neuromyelitis optica, a healthy group, and a sham group. We analyzed differentiation capacity in cultures of neurospheres from the subventricular zone of mice by adding serum at two different times: early and advanced stages of differentiation. We also analyzed differentiation into different cell lines. Results and Conclusions: The effect of sera from patients with NMOSD on precursor cells differs according to the degree of differentiation, and probably affects oligodendrocyte progenitor cells from NG2 cells to a lesser extent than cells from the subventricular zone; however, the resulting oligodendrocytes may be compromised in terms of maturation and possibly limited in their ability to generate myelin. Furthermore, these cells decrease in number with age. It is very unlikely that the use of drugs favoring the migration and differentiation of oligodendrocyte progenitor cells in multiple sclerosis would be effective in the context of neuromyelitis optica, but cell therapy with oligodendrocyte progenitor cells seems to be a potential alternative

The Integration of Cell Therapy and Biomaterials as Treatment Strategies for Remyelination

Multiple sclerosis (MS) is a chronic degenerative autoimmune disease of the central nervous system that causes inflammation, demyelinating lesions, and axonal damage and is associated with a high rate of early-onset disability. Disease-modifying therapies are used to mitigate the inflammatory process in MS but do not promote regeneration or remyelination; cell therapy may play an important role in these processes, modulating inflammation and promoting the repopulation of oligodendrocytes, which are responsible for myelin repair. The development of genetic engineering has led to the emergence of stable, biocompatible biomaterials that may promote a favorable environment for exogenous cells. This review summarizes the available evidence about the effects of transplantation of different types of stem cells reported in studies with several animal models of MS and clinical trials in human patients. We also address the advantages of combining cell therapy with biomaterials

Adult Prevalence of Epilepsy in Spain: EPIBERIA, a Population-Based Study

Background. This study assesses the lifetime and active prevalence of epilepsy in Spain in people older than 18 years. Methods. EPIBERIA is a population-based epidemiological study of epilepsy prevalence using data from three representative Spanish regions (health districts in Zaragoza, Almería, and Seville) between 2012 and 2013. The study consisted of two phases: screening and confirmation. Participants completed a previously validated questionnaire (EPIBERIA questionnaire) over the telephone. Results. A total of 1741 valid questionnaires were obtained, including 261 (14.99%) raising a suspicion of epilepsy. Of these suspected cases, 216 (82.75%) agreed to participate in phase 2. Of the phase 2 participants, 22 met the International League Against Epilepsy’s diagnostic criteria for epilepsy. The estimated lifetime prevalence, adjusted by age and sex per 1,000 people, was 14.87 (95% CI: 9.8–21.9). Active prevalence was 5.79 (95% CI: 2.8–10.6). No significant age, sex, or regional differences in prevalence were detected. Conclusions. EPIBERIA provides the most accurate estimate of epilepsy prevalence in the Mediterranean region based on its original methodology and its adherence to ILAE recommendations. We highlight that the lifetime prevalence and inactive epilepsy prevalence figures observed here were compared to other epidemiological studies

Underpinnings of verbal fluency in Multiple Sclerosis

Publicado en la sección CorrespondenceThe cognitive and language processes underlying verbal fluency remain unclear. While some cognitive processes related to memory and executive functioning have been more associated with category and letter verbal fluency, other less studied aspects of language ability could be also related. We discuss the contribution of the recent study by Lebkuecher and colleagues (2021) about the role of language in verbal fluency, and the data from other studies evaluating the cognitive and neuroimaging correlates of verbal fluency in MSInstituto de Salud Carlos IIIEuropean CommissionDepto. de Psicobiología y Metodología en Ciencias del ComportamientoFac. de PsicologíaTRUEpu