Developmental expression of 4-repeat-Tau induces neuronal aneuploidy in Drosophila tauopathy models

Tau-mediated neurodegeneration in Alzheimer's disease and tauopathies is generally assumed to start in a normally developed brain. However, several lines of evidence suggest that impaired Tau isoform expression during development could affect mitosis and ploidy in post-mitotic differentiated tissue. Interestingly, the relative expression levels of Tau isoforms containing either 3 (3R-Tau) or 4 repeats (4R-Tau) play an important role both during brain development and neurodegeneration. Here, we used genetic and cellular tools to study the link between 3R and 4R-Tau isoform expression, mitotic progression in neuronal progenitors and post-mitotic neuronal survival. Our results illustrated that the severity of Tau-induced adult phenotypes depends on 4R-Tau isoform expression during development. As recently described, we observed a mitotic delay in 4R-Tau expressing cells of larval eye discs and brains. Live imaging revealed that the spindle undergoes a cycle of collapse and recovery before proceeding to anaphase. Furthermore, we found a high level of aneuploidy in post-mitotic differentiated tissue. Finally, we showed that overexpression of wild type and mutant 4R-Tau isoform in neuroblastoma SH-SY5Y cell lines is sufficient to induce monopolar spindles. Taken together, our results suggested that neurodegeneration could be in part linked to neuronal aneuploidy caused by 4R-Tau expression during brain development

Efficacy and Safety of Transcranial Electric Stimulation during the Perinatal Period: A Systematic Literature Review and Three Case Reports

International audienceIntroduction: The perinatal period is an at-risk period for the emergence or decompensation of psychiatric disorders. Transcranial electrical stimulation (tES) is an effective and safe treatment for many psychiatric disorders. Given the reluctance to use pharmacological treatments during pregnancy or breastfeeding, tES may be an interesting treatment to consider. Our study aims to evaluate the efficacy and safety of tES in the perinatal period through a systematic literature review followed by three original case reports. Method: Following PRISMA guidelines, a systematic review of MEDLINE and ScienceDirect was undertaken to identify studies on tES on women during the perinatal period. The initial research was conducted until 31 December 2021 and search terms included: tDCS, transcranial direct current stimulation, tACS, transcranial alternating current stimulation, tRNS, transcranial random noise stimulation, pregnancy, perinatal, postnatal, and postpartum. Results: Seven studies reporting on 33 women during the perinatal period met the eligibility criteria. No serious adverse effects for the mother or child were reported. Data were limited to the use of tES during pregnancy in patients with schizophrenia or unipolar depression. In addition, we reported three original case reports illustrating the efficacy and safety of tDCS: in a pregnant woman with bipolar depression, in a pregnant woman with post-traumatic stress disorder (sham tDCS), and in a breastfeeding woman with postpartum depression. Conclusions: The results are encouraging, making tES a potentially safe and effective treatment in the perinatal period. Larger studies are needed to confirm these initial results, and any adverse effects on the mother or child should be reported. In addition, research perspectives on the medico-economic benefits of tES, and its realization at home, are to be investigated in the future

Efficacy and Safety of Transcranial Electric Stimulation during the Perinatal Period: A Systematic Literature Review and Three Case Reports

Introduction: The perinatal period is an at-risk period for the emergence or decompensation of psychiatric disorders. Transcranial electrical stimulation (tES) is an effective and safe treatment for many psychiatric disorders. Given the reluctance to use pharmacological treatments during pregnancy or breastfeeding, tES may be an interesting treatment to consider. Our study aims to evaluate the efficacy and safety of tES in the perinatal period through a systematic literature review followed by three original case reports. Method: Following PRISMA guidelines, a systematic review of MEDLINE and ScienceDirect was undertaken to identify studies on tES on women during the perinatal period. The initial research was conducted until 31 December 2021 and search terms included: tDCS, transcranial direct current stimulation, tACS, transcranial alternating current stimulation, tRNS, transcranial random noise stimulation, pregnancy, perinatal, postnatal, and postpartum. Results: Seven studies reporting on 33 women during the perinatal period met the eligibility criteria. No serious adverse effects for the mother or child were reported. Data were limited to the use of tES during pregnancy in patients with schizophrenia or unipolar depression. In addition, we reported three original case reports illustrating the efficacy and safety of tDCS: in a pregnant woman with bipolar depression, in a pregnant woman with post-traumatic stress disorder (sham tDCS), and in a breastfeeding woman with postpartum depression. Conclusions: The results are encouraging, making tES a potentially safe and effective treatment in the perinatal period. Larger studies are needed to confirm these initial results, and any adverse effects on the mother or child should be reported. In addition, research perspectives on the medico-economic benefits of tES, and its realization at home, are to be investigated in the future

Efficacy and Safety of Transcranial Electric Stimulation during the Perinatal Period: A Systematic Literature Review and Three Case Reports

International audienceIntroduction: The perinatal period is an at-risk period for the emergence or decompensation of psychiatric disorders. Transcranial electrical stimulation (tES) is an effective and safe treatment for many psychiatric disorders. Given the reluctance to use pharmacological treatments during pregnancy or breastfeeding, tES may be an interesting treatment to consider. Our study aims to evaluate the efficacy and safety of tES in the perinatal period through a systematic literature review followed by three original case reports. Method: Following PRISMA guidelines, a systematic review of MEDLINE and ScienceDirect was undertaken to identify studies on tES on women during the perinatal period. The initial research was conducted until 31 December 2021 and search terms included: tDCS, transcranial direct current stimulation, tACS, transcranial alternating current stimulation, tRNS, transcranial random noise stimulation, pregnancy, perinatal, postnatal, and postpartum. Results: Seven studies reporting on 33 women during the perinatal period met the eligibility criteria. No serious adverse effects for the mother or child were reported. Data were limited to the use of tES during pregnancy in patients with schizophrenia or unipolar depression. In addition, we reported three original case reports illustrating the efficacy and safety of tDCS: in a pregnant woman with bipolar depression, in a pregnant woman with post-traumatic stress disorder (sham tDCS), and in a breastfeeding woman with postpartum depression. Conclusions: The results are encouraging, making tES a potentially safe and effective treatment in the perinatal period. Larger studies are needed to confirm these initial results, and any adverse effects on the mother or child should be reported. In addition, research perspectives on the medico-economic benefits of tES, and its realization at home, are to be investigated in the future

Developmental Expression of 4-Repeat-Tau Induces Neuronal Aneuploidy in Drosophila Tauopathy Models

Tau-mediated neurodegeneration in Alzheimer's disease and tauopathies is generally assumed to start in a normally developed brain. However, several lines of evidence suggest that impaired Tau isoform expression during development could affect mitosis and ploidy in post-mitotic differentiated tissue. Interestingly, the relative expression levels of Tau isoforms containing either 3 (3R-Tau) or 4 repeats (4R-Tau) play an important role both during brain development and neurodegeneration. Here, we used genetic and cellular tools to study the link between 3R and 4R-Tau isoform expression, mitotic progression in neuronal progenitors and post-mitotic neuronal survival. Our results illustrated that the severity of Tau-induced adult phenotypes depends on 4R-Tau isoform expression during development. As recently described, we observed a mitotic delay in 4R-Tau expressing cells of larval eye discs and brains. Live imaging revealed that the spindle undergoes a cycle of collapse and recovery before proceeding to anaphase. Furthermore, we found a high level of aneuploidy in post-mitotic differentiated tissue. Finally, we showed that overexpression of wild type and mutant 4R-Tau isoform in neuroblastoma SH-SY5Y cell lines is sufficient to induce monopolar spindles. Taken together, our results suggested that neurodegeneration could be in part linked to neuronal aneuploidy caused by 4R-Tau expression during brain development.status: publishe

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population