Neuroscientist最新文献

The object of this article is a drawing by Peter Paul Rubens, a copy of "The Battle of Anghiari" by Leonardo da Vinci in 1503-1506. This work, created in 1603, was based on an engraving of 1553 by Lorenzo Zacchia, which was taken from a cartoon by Leonardo da Vinci. The original fresco itself is lost. The analysis of the drawing shows that the Peter Paul Rubens's copy of "The Battle of Anghiari" by Leonardo da Vinci, which was created six centuries ago, includes double content. The drawing depicting the battle secretly describes the three-dimensional image of the brain.

Dravet syndrome is a severe developmental and epileptic encephalopathy mostly caused by heterozygous mutation of the SCN1A gene encoding the voltage-gated sodium channel α subunit Na_v1.1. Multiple seizure types, cognitive deterioration, behavioral disturbances, ataxia, and sudden unexpected death associated with epilepsy are a hallmark of the disease. Recently approved antiseizure medications such as fenfluramine and cannabidiol have been shown to reduce seizure burden. However, patients with Dravet syndrome are still medically refractory in the majority of cases, and there is a high demand for new therapies aiming to improve behavioral and cognitive outcome. Drug-repurposing approaches for SCN1A-related Dravet syndrome are currently under investigation (i.e., lorcaserin, clemizole, and ataluren). New therapeutic concepts also arise from the field of precision medicine by upregulating functional SCN1A or by activating Na_v1.1. These include antisense nucleotides directed against the nonproductive transcript of SCN1A with the poison exon 20N and against an inhibitory noncoding antisense RNA of SCN1A. Gene therapy approaches such as adeno-associated virus-based upregulation of SCN1A using a transcriptional activator (ETX101) or CRISPR/dCas technologies show promising results in preclinical studies. Although these new treatment concepts still need further clinical research, they offer great potential for precise and disease modifying treatment of Dravet syndrome.

Narcolepsy is a sleep disorder manifesting symptoms such as excessive daytime sleepiness and often cataplexy, a sudden and involuntary loss of muscle activity during wakefulness. The underlying neuropathological basis of narcolepsy is the loss of orexin neurons from the lateral hypothalamus. To date numerous animal models of narcolepsy have been produced in the laboratory, being invaluable tools for delineating the brain circuits of narcolepsy. This review will examine the evidence regarding the function of the orexin system, and how loss of this wake-promoting system manifests in excessive daytime sleepiness. This review will also outline the brain circuits controlling cataplexy, focusing on the contribution of orexin signaling loss in narcolepsy. Although our understanding of the brain circuits of narcolepsy has made great progress in recent years, much remains to be understood.

The use of digital technologies is constantly growing around the world. The wider-spread adoption of digital technologies and solutions in the daily clinical practice in psychiatry seems to be a question of when, not if. We propose a synthesis of the scientific literature on digital technologies in psychiatry and discuss the main aspects of its possible uses and interests in psychiatry according to three domains of influence that appeared to us: 1) assist and improve current care: digital psychiatry allows for more people to have access to care by simply being more accessible but also by being less stigmatized and more convenient; 2) develop new treatments: digital psychiatry allows for new treatments to be distributed via apps, and practical guidelines can reduce ethical challenges and increase the efficacy of digital tools; and 3) produce scientific and medical knowledge: digital technologies offer larger and more objective data collection, allowing for more detection and prevention of symptoms. Finally, ethical and efficacy issues remain, and some guidelines have been put forth on how to safely use these solutions and prepare for the future.

Noninvasive brain stimulation (NIBS) techniques are widely used tools for the study and rehabilitation of cognitive functions. Different NIBS approaches aim to enhance or impair different cognitive processes. The methodological focus for achieving this has been on stimulation protocols that are considered either inhibitory or facilitatory. However, despite more than three decades of use, their application is based on incomplete and overly simplistic conceptualizations of mechanisms of action. Such misconception limits the usefulness of these approaches in the basic science and clinical domains. In this review, we challenge this view by arguing that stimulation protocols themselves are neither inhibitory nor facilitatory. Instead, we suggest that all induced effects reflect complex interactions of internal and external factors. Given these considerations, we present a novel model in which we conceptualize NIBS effects as an interaction between brain activity and the characteristics of the external stimulus. This interactive model can explain various phenomena in the brain stimulation literature that have been considered unexpected or paradoxical. We argue that these effects no longer seem paradoxical when considered from the viewpoint of state dependency.

Iron accumulation in the CNS occurs in many neurological disorders. It can contribute to neuropathology as iron is a redox-active metal that can generate free radicals. The reasons for the iron buildup in these conditions are varied and depend on which aspects of iron influx, efflux, or sequestration that help maintain iron homeostasis are dysregulated. Iron was shown recently to induce cell death and damage via lipid peroxidation under conditions in which there is deficient glutathione-dependent antioxidant defense. This form of cell death is called ferroptosis. Iron chelation has had limited success in the treatment of neurological disease. There is therefore much interest in ferroptosis as it potentially offers new drugs that could be more effective in reducing iron-mediated lipid peroxidation within the lipid-rich environment of the CNS. In this review, we focus on the molecular mechanisms that induce ferroptosis. We also address how iron enters and leaves the CNS, as well as the evidence for ferroptosis in several neurological disorders. Finally, we highlight biomarkers of ferroptosis and potential therapeutic strategies.

Microglia are critical players in the neuroimmune system, and their involvement in Alzheimer's disease (AD) pathogenesis is increasingly being recognized. However, whether microglia play a positive or negative role in AD remains largely controversial and the precise molecular targets for intervention are not well defined. This partly results from the opposing roles of microglia in AD pathology, and is mainly reflected in the microglia-neuron interaction. Microglia can prune synapses resulting in excessive synapse loss and neuronal dysfunction, but they can also promote synapse formation, enhancing neural network plasticity. Neuroimmune crosstalk accelerates microglial activation, which induces neuron death and enhances the microglial phagocytosis of β-amyloid to protect neurons. Moreover, microglia have dual opposing roles in developing the major pathological features in AD, such as amyloid deposition and blood-brain barrier permeability. This review summarizes the dual opposing role of microglia in AD from the perspective of the interaction between neurons and microglia. Additionally, current AD treatments targeting microglia and the advantages and disadvantages of developing microglia-targeted therapeutic strategies are discussed.