Reviews in the Neurosciences最新文献

Subarachnoid hemorrhage (SAH) induces early brain injury (EBI) through mechanisms involving mitochondrial dysfunction and dysregulated calcium signaling. Transient receptor potential canonical (TRPC) channels are critical mediators of calcium homeostasis and have emerged as key players in SAH pathophysiology. This review explores the interconnected roles of TRPC channel-mediated calcium dyshomeostasis and mitophagy in EBI. We summarize how mitochondrial damage post-SAH triggers mitophagy via ubiquitin-dependent and -independent pathways, a process with dual effects on neuronal survival. We then detail the dual-phase roles of TRPC subtypes: early neuroprotection via TRPC1/4 and later exacerbation of injury via TRPC3/6/7, linking their activation to vascular dysfunction and inflammation. Crucially, we propose and discuss the mechanistic links through which TRPC-mediated calcium signals may directly regulate mitophagic flux, thereby influencing EBI outcomes. Targeting this TRPC-mitophagy axis with subtype- and temporal-specific strategies holds therapeutic promise for SAH.

The researchers who conduct, author and review neuroscience studies inherently shape both the findings and the segments of society that ultimately benefit from the research. Generally, Western high-income nations dominate the production and dissemination of the majority of prestigious scientific research. However, the extent of geographic disparities across the neuroscience research pipeline, including at the level of editors, peer reviewers, authors, and research participants, have not been examined. This article synthesizes meta-research studies examining geographic disparities in neuroscience research, supplemented by an analysis of the properties of 2,013 articles published in the top five most prestigious neuroscience journals between 2014 and 2023. Our review demonstrates that editorial boards and authorship of neuroscience research remains concentrated in high-income Western nations, with some evidence to suggest that authors affiliated with non-high-income nations are increasingly represented. There is currently no direct evidence to suggest that authors affiliated with non-high-income countries experience disparities in peer review delays or public engagement with their research. However, our analysis shows that these authors' works receive fewer citations than their high-income nation-affiliated colleagues'. Further, while very few non-high-income nation-affiliated researchers first-author prestigious neuroscience publications, a relatively greater proportion of these prestigious publications use data from research participants in non-high-income nations. We conclude the review by summarizing current initiatives aimed at reducing geographic disparities in neuroscience research.

Decision making is frequently influenced by factors such as an individual's emotional state, cognitive biases, social influences, and environmental constraints. Understanding how these factors influence the way decisions are made is essential for optimizing and improving this cognitive process. Therefore, this review examines the theoretical basis of emotion-influenced decision making. Here, we integrate insights from eye-tracking, electroencephalography (EEG), and magnetic resonance imaging (MRI) evidence, as well as behavioral findings. We specifically review evidence from studies applying the Wheel of Fortune Gambling Task paradigm. Through critical and reflective synthesis, we (1) present suggestions for distinguishing between emotion types in decision-making theoretical models, (2) identify key research gaps, and (3) explore innovative applications of emerging technologies. In essence, our review highlights the role of diverse emotions in decision making across theoretical models and neural mechanisms, utilizing the Wheel of Fortune Gambling Task paradigm to link clinical disorders with decision-making impairments. This knowledge may have implications for predicting and intervening in behavioral addictions and cognitive disorders through strategies such as the neuromodulation. Additionally, by synthesizing existing knowledge and proposing new avenues for research, this review aims to deepen understanding of emotion-driven decision making and inspire further exploration into this vital area of cognitive science.

Since the 19th century, the study of brain mechanisms of language has depended on available tools: the clinical study of language-impaired patients, with neuropathological correlates, in the style of Broca and Wernicke; imaging techniques including MRI, functional MRI, and MRI tractography; and direct stimulation of, and recording from, the brains of conscious patients performing language tasks. These tasks can be directed or spontaneous and occur typically in the course of evaluations prior to surgery or intraoperatively. The study of brain and language occurs in the context of classical linguistics, with its (relative) distinctions between semantics and syntax, and its requirements for formal analysis in the latter. A consequence has been the effort to parcellate regions of the left hemisphere (of most individuals) in terms of distinct linguistic functions, and to characterize the anatomical connections between parcels: the various fascicles. In parallel, invasive brain recordings of activity at the level of networks or multiple single cells have allowed correlation of localized electrical signals with linguistic parameters. Recently, however, a paradigm shift has begun concerning the proper framework for interpreting language-related brain measurements. Partly this has occurred because of the success of large language models (LLMs), which do not include explicit dependence on formal syntactic/semantic distinctions. As a result, electrical brain measurements are now examined with a focus on interactions between multiple small cortical "modules." In this paper, we examine the cellular physiology underlying the activities of modules and their interactions, with emphasis on the mechanisms and functions of fast brain oscillations.

Ketone therapies refer to metabolic interventions aimed to elevate circulating levels of ketone bodies (KB), either through direct supplementation or stimulating endogenous production via medium-chain fatty acids intake, ketogenic diets, caloric restriction, intermittent fasting, or exercise. These strategies have gained attention as potential treatments for neurodegenerative diseases by preserving neuronal function, improving metabolic efficiency, and enhancing cellular resilience to stress. KB are taken up and metabolized by various brain cell types-including neurons, astrocytes, oligodendroglia and microglia-under basal and pathological conditions. However, their cell-type-specific effects remain incompletely understood. Notably, although astrocytes play a key role in supporting neuronal metabolism and can both produce and utilize KB, research has focused predominantly on neuronal responses, leaving the impact of ketotherapeutics on astrocytes relatively unexplored. This review aims to compile and discuss current evidence concerning astrocytes responses to both exogenous and endogenous ketotherapeutic strategies. Although still limited, available studies reveal that astrocytes undergo dynamic changes in response to these interventions, including morphological remodeling, calcium signaling modulation, transcriptional and metabolic reprogramming, regulation of transporters, and neurotransmitter uptake-a crucial process for synaptic function. Astrocytes appear to actively contribute to the neuroprotective and pro-cognitive effects of ketone therapies, particularly in the context of aging and disease. However, significant gaps still remain, concerning the stage when ketone therapy should be initiated, the underlying mechanisms, regional specificity, and long-term consequences. Future research focused on astrocyte heterogeneity, activation of intracellular pathways, and metabolic and transcriptional reprogramming will enable the translational potential of astrocyte-targeted ketone therapies for neurological disorders.

The development of substance use disorders (SUDs) is partly determined by genetic factors. Brain-derived neurotrophic factor (BDNF) underlies the neurobiological mechanisms of action of psychoactive substances (PASs) and development of SUDs, while genetic markers within the BDNF gene may be associated with a risk of SUDs and accompanied clinical manifestations. This is a systematic review of the relationships between single nucleotide polymorphisms (SNPs) within the BDNF gene locus and various aspects of SUDs. We searched, appraised, and summarized the research evidence of these associations for the main pharmacological groups of PASs (tobacco, cannabis, alcohol, opioids, and stimulants). Most studies have focused on the functional Val66Met (rs6265) polymorphism. They demonstrated that the rs6265 Met (T) allele may be a protective factor for the development of SUDs. In addition to rs6265, other individual BDNF-related SNPs and the corresponding haplotypes were associated with the risk of the development of SUDs, their clinical manifestations, presence of comorbidity, and sensitivity to pharmacotherapy. The identified associations often depended on the studied population and were influenced by sex and ancestry. Established BDNF-related genetic markers or their combinations potentially may be used as objective diagnostic or prognostic criteria in clinical practice.

Elucidating the factors that influence the recovery of impaired consciousness in patients with prolonged disorders of consciousness (pDoC) is essential for guiding neurorehabilitation strategies and improving prognostic accuracy. This review synthesizes evidence from multiple studies that investigated prognostic factors in pDoC using various approaches, including clinical and demographic characteristics, biomarkers, behavioral assessments, pharmacological treatments, neuromodulation techniques, neuroimaging, and electroencephalography. Results indicate that several indicators show significant correlations with functional outcomes at follow-up intervals ranging from 2 months to several years. These findings assist in selecting appropriate assessment tools and support clinical decision-making for pDoC patients. However, limitations such as small sample sizes, absence of control groups, and heterogeneity in follow-up durations were noted across studies. The development of large-scale, multimodal prognostic models is warranted to enhance clinical applicability and predictive power.

Chronic social isolation stress (CSIS) is a well-established preclinical model for studying stress-induced neurobiological changes and their effects on behavior and brain function in depression. The prefrontal cortex (PFC), a brain region essential for emotional regulation, cognitive control, and social interactions, is particularly susceptible to stress. While CSIS exposure triggers molecular and behavioral changes characteristic of depression-like behavior, a subset of animals displays a resilient phenotype, maintaining normal neurobiological and behavioral function despite experiencing adverse conditions. Understanding the molecular differences between resilient and susceptible phenotypes is crucial for identifying biomarkers and developing novel therapeutic targets for depression. Mass spectrometry-based proteomics, combined with bioinformatics approaches, provides a powerful tool for exploring these complex cellular processes. This review focuses on proteomic changes in cytosolic and synaptosome-enriched fractions of the PFC in adult male rats following CSIS exposure, with particular emphasis on differences between resilient and susceptible animals. We summarize findings of differential protein expression across multiple biological systems, including energy metabolism, cytoskeletal organization, cellular stress defense mechanisms, neurotransmitter regulation, and synaptic function. Additionally, we present protein predictors of resilience to CSIS identified through machine learning-based analyses, highlighting potential pathways for preventing and mitigating depression-like outcomes following CSIS.

Epilepsy is a neurological condition that affects around 50 million people globally. While the underlying mechanism of epilepsy is not fully understood, emerging evidence demonstrates that inflammation is a key player in the pathogenesis of epilepsy. MicroRNAs are involved in the pathogenesis of epilepsy, particularly through regulating oxidative stress, apoptosis, and inflammation. In this systematic review, we analyzed and summarized data from the literature regarding the role of inflammatory miRNAs in the pathophysiology of epilepsy, through human and animal studies. Twenty one reports on humans and 44 reports on animals were included in the current analysis. Kainic acid (KA) and pilocarpine were broadly used approaches in inducing epilepsy in animal models. Among upregulated microRNAs, miR-146a, miR-155, and miR-132 were more emphasized for their inflammatory role involved in epilepsy. MiR-221, miR-222, and miR-29a were downregulated and were associated with anti-inflammatory effects. Notably, microRNAs demonstrated tissue-specific expression patterns in different samples, including brain cortex, hippocampus, and body fluids, which is considerable in further investigations in the pathophysiologic and diagnostic roles of inflammatory microRNAs in epilepsy. Furthermore, inflammatory miRNAs regulate critical signaling pathways like TLR4/NF-κB, PI3K/Akt, and IL-1β-mediated neuroinflammation. Conclusively, these findings highlight the possibility of using inflammatory miRNAs as diagnostic biomarkers and therapeutic targets of epilepsies.

For several decades, the modeling of brain diseases in experimental animals has remained one of the key components of studying the pathogenesis of central nervous system pathology and searching for new methods of prevention and therapy. In recent years, new approaches to modeling pathological conditions in vitro have been in active development; these approaches will not only reduce the number of animal studies but also allow us to take a step toward reproducing the human-specific mechanisms of brain pathology. In this review, we characterize the most common rodent models of cerebral ischemia and reperfusion, as well as neuroinflammation inherent to neurodegeneration (in particular, Parkinson's disease), which are reproduced in vivo. This review addresses engineering and technical challenges and the prospects for the development of brain pathology models in vitro, e.g., vascularized and microglia-containing/neuroimmune cerebral organoids, which may be useful in overcoming the shortcomings and limitations of the current in vivo models.