Reviews in the Neurosciences最新文献

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is marked by cognitive decline, neuroinflammation, and neuronal loss. MicroRNAs (miRNAs) have emerged as critical regulators of gene expression, influencing key pathways involved in neuroinflammation and neurodegeneration in AD. This review delves into the multifaceted role of exercise in modulating miRNA expression and its interplay with the gut microbiome, proposing a comprehensive framework for neuroprotection in AD. By synthesizing current research, we elucidate how exercise-induced changes in miRNA profiles can mitigate inflammatory responses, promote neurogenesis, and reduce amyloid-beta and tau pathologies. Additionally, we explore the gut-brain axis, highlighting how exercise-driven alterations in gut microbiota composition can further influence miRNA expression, thereby enhancing cognitive function and reducing neuroinflammatory markers. This holistic approach underscores the potential of targeting exercise-regulated miRNAs and gut microbiome interactions as a novel, noninvasive therapeutic strategy to decelerate AD progression and improve quality of life for patients. This approach aims to decelerate disease progression and improve patient outcomes, offering a promising avenue for enhancing the effectiveness of AD management.

We constructed a computational thalamocortical network model for study of the neocortical slow oscillation. It incorporated a number of neuronal types, both excitatory and inhibitory, each model neuron simulated as a multicompartment entity with numerous membrane conductances. As in previous experimental and modeling studies, simulated slow oscillations primarily depended on recurrently connected deep intrinsic bursting (IB) pyramidal cells, with NMDA receptors being critical as well as intrinsic membrane conductances (e.g. persistent Na⁺); and with repolarization to the Down state dependent on intrinsic (slow Ca²⁺-dependent K⁺) and synaptic (GABA_B receptor mediated) conductances. Furthermore, however, we now can account for additional features of the slow oscillation: the frequent occurrence of spikelets, the presence of very fast ripple-like oscillations, and the transition to so-called fast runs (10 to ∼20 Hz bursty oscillations). These latter phenomena depended in our model on electrical coupling via gap junctions between pyramidal neurons. The importance of gap junctions is supported by previous experimental data on the ripple-blocking effect of halothane, as well as by data from the in vitro hippocampus.

Depression remains one of the most common and debilitating neuropsychiatric conditions, with little consistency in treatment efficacy. Some of the lack of success in developing effective treatments has been the absence of a reliable biomarker of depression, despite many attempts. One such potential biomarker is the electrical activity of the brain that occurs in the gamma band (30-200 Hz). To evaluate the state of research into gamma as a biomarker of depression, a review of recent research literature was conducted. A total of 31 relevant papers was identified, 22 of which used resting-state studies, and nine included a stimulus-task. These studies were examined here in terms of their definition of gamma, sample sizes, research focus, brain region examined, and EEG methodologies used. Due to the range of methodologies, some inconsistent results emerged but several valuable findings remained, including that depressed patients usually had higher gamma power than their healthy controls (HC), that the imposition of a perceptual task into the research protocol also introduced a strong element of confound to the results, and that studies that sought to evaluate the role of gamma in treatment were yet to be established as reliable. Key issues for future research are discussed, and the potential for gamma as a biomarker of depression is evaluated as emerging.

Epilepsy encompasses a group of chronic brain disorders characterized by recurrent, hypersynchronous activity of neuronal clusters, with epileptic seizures being the primary manifestation of these disorders. The objective of epilepsy treatment is to prevent seizures with minimum adverse side effects. However, approximately 30 % of patients do not respond to available medications. One proposed mechanism of epileptogenesis is glutamate excitotoxicity. When released in excess or not appropriately removed from the synaptic cleft, glutamate hyperactivates receptors, causing a biochemical cascade, which culminates in seizures and cell death. The use of animal models is essential for uncovering potential epileptogenic pathways, understanding the role of receptors and transporters in excitotoxicity, and screening effective antiepileptic treatments. This review examines studies that investigate the role of glutamate transporters and receptors in excitotoxicity and epileptogenesis using animal models. For this, we searched through both PubMed/Medline and ScienceDirect databases. After applying the inclusion and exclusion criteria, 26 (twenty-six) studies were selected for analysis. The studies addressed key glutamate transporter family of excitatory amino acid transporters (EAATs) EAAT1, EAAT2, and EAAT3, responsible for glutamate clearance, as well as AMPA receptor subunits GluA1 and GluA2, NMDA receptor subunits GluN1, GluN2a, and GluN2b, and the metabotropic receptors mGluR5 and mGluR2/3. Results showed that the dysregulation of these transporters and receptors is associated to seizure induction and excitotoxic damage, pointing to their fundamental role in the mechanisms of excitotoxicity and epileptogenesis. These findings highlight the potential of targeting glutamate transporters and receptors to stabilize glutamate homeostasis as an intervention in epilepsy management.

Diabetic peripheral neuropathy (DPN) is a serious complication of diabetes mellitus, which is a common cause of disability in individuals with diabetes mellitus. Multiple mechanisms may be involved in the development of DPN. Neuroinflammation is a critical factor contributing to nerve damage during diabetes. Inflammation can induce the development of diabetes mellitus, and long-term hyperglycemia also causes increased oxidative stress and promotes the release of inflammatory cytokines. After reading through the literature, the association of inflammation with the induction of diabetes and DPN was discussed in the review. Inflammation induces nerve damage and nerve conduction impairment. The neuropathic pain in diabetes-induced DPN is also closely associated with the inflammatory response. Given the important roles of inflammation in diabetes-induced DPN, explicit elucidation of neuroinflammation during diabetes mellitus and DPN should hold the potential for developing novel therapeutic strategies for DPN. Experimental studies and limited clinical trials support the value of anti-inflammatory reagents in treating DPN, and the positive outcomes of these investigations warrant further clinical trials.

Tryptophan (TRP) metabolism produces various neuroactive substances in the gastrointestinal tract, as well as in the central and peripheral nervous systems and intestinal microbiota. Initially centered on the serotonin pathway in TRP metabolism and TRP itself, many studies are now focusing on the kynurenine pathway, with an increasing interest in the indole pathway. Several TRP metabolites have been associated with migraines, suggesting that TRP metabolism may serve as a potential therapeutic target. However, these studies have significant limitations, including a small number of participants, a lack of standardized diets prior to and/or during clinical trials, and insufficient information regarding the transformation of TRP after its intake. Furthermore, no thorough study encompasses all the essential components of TRP metabolism: products, enzymes, receptors, and transporters. Different mechanisms may explain the involvement of TRP metabolism in migraines, including glutamate signaling and neurovasodilatory, immune, oxidative, and inflammatory processes. The results of studies on the role of TRP metabolism in migraine may be helpful for making dietary recommendations for migraine prevention and clinical management; however, individual characteristics for metabolizing TRP should be considered. The aim of this narrative perspective review is to critically present the results of studies on the role of TRP metabolism in migraine and explore their implications for migraine prevention and therapy. Unlike many other reviews that focus solely on either the serotonin or kynurenine pathway, our paper addresses all three primary TRP metabolism pathways.

Glutamate is not only the main excitatory neurotransmitter of the human central nervous system, but also a potent neurotoxin. Therefore, maintaining low-dose, non-toxic extracellular glutamate concentrations between synapses to ensure the reliability of synaptic transmission is essential for maintaining normal physiological functions of neurons. More and more studies have confirmed that the specific pathogenesis of central nervous system diseases (such as Alzheimer's disease) caused by neuronal damage or death due to abnormal inter-synaptic glutamate concentration may be related to the abnormal function of excitatory amino acid transporter proteins and glutamine synthetase on astrocytes, and that the abnormal expression and function of the above two proteins may be related to the transcription, translation, and even modification of both by the process of transcription, translation, and even modification of astrocytes. oxidative stress, and inflammatory responses occurring in astrocytes during their transcription, translation and even modification. Therefore, in this review, we mainly discuss the relationship between glutamate metabolism (from postsynaptic neurons to astrocytes), Alzheimer's disease and Parkinson's disease in recent years.

Dialectical thinking represents a cognitive style emphasizing change, contradiction, and holism. Cross-cultural studies reveal a stark contrast of dialectical thinking between East Asian and Western cultures, highlighting East Asians' superior ability to embrace contradictions and foresee transformation, fostering psychological resilience through emotional complexity and tolerance for contradictions. Despite its importance, the neural basis of dialectical thinking remains underexplored. This review synthesizes current neuroscientific findings and introduces the dialectical-integration network (DIN) hypothesis, which identifies key brain regions such as the dorsal anterior cingulate cortex (dACC), medial prefrontal cortex (mPFC), dorsal lateral prefrontal cortex (DLPFC), nucleus accumbens, basal ganglia, and amygdala. These regions, along with networks like the default mode network (DMN) and frontoparietal network (FPN), facilitate holistic reasoning, conflict resolution, and sensory-emotional integration. The psychological benefits of dialectical thinking include enhanced cognitive flexibility, reduced emotional extremes, and improved conflict resolution. This review emphasizes the need for cross-cultural and neuroscientific research to explore the principle of change, a core aspect of dialectical cognition. By bridging cultural psychology and cognitive neuroscience, this work offers theoretical and methodological insights into culturally shaped cognitive styles, with practical applications in education, mental health, and intercultural communication. The DIN model provides a framework for future research on dynamic neural interactions supporting dialectical thinking.

Despite significant progress in managing HIV infection, HIV - associated neurocognitive disorder (HAND) continues to be a concern even among HIV individuals with well - controlled infection. Current diagnostic strategies, primarily reliant on neuropsychological tests, neuroimaging, and biomarkers from blood and cerebrospinal fluid, alongside combination antiretroviral therapy, form the foundation of HAND management. However, these strategies often fail to identify early or mild HAND, particularly asymptomatic neurocognitive impairment, resulting in delayed diagnosis and intervention. Furthermore, the inability to perform in-depth molecular analyses and conduct longitudinal tracking limits therapeutic advancements. Emerging technologies - advanced neuroimaging, multi-omics, artificial intelligence, alongside simian immunodeficiency virus non-human primate models - are revolutionizing the field. These innovations offer unprecedented opportunities for deeper understanding of the disease mechanism, early detection, comprehensive monitoring, and personalized treatment strategies. Integrating these cutting-edge tools promises to reshape the landscape of HAND management, enhancing the quality of life for those living with HIV.

Within the concept of the extended mind, the active modification of external objects, externalizations, is seen as an auxiliary means to adapt to the environment. Toolmaking and use are advanced stages of externalizations that evolve. All past or present tools can, theoretically, be precisely assigned a location in an evolutionary tree with predecessors and progeny. Tools are reliably replicated, modified, and selected by their ability to facilitate human needs. Tool evolution, therefore, fulfills Darwinian criteria where the material tool is the phenotype and the instruction to build it is the code. The ostensive triangle consisting of a pointing individual, an observing individual, and a pointed-at object or tool is the germ cell of social transmission of instructions. Tool-building instructions ultimately can be reduced to distinct sequences of motor acts that can be recombined and are socially transmitted. When executed, they replicate tools for the reward of convenience or improved fitness. Tools elicit affordances relating to their use that synchronize different individuals' perceptions, result in psychological "understanding," and thereby modify social networks. Massive tool fabrication as present today in the "tool-sphere" has, therefore, accelerated prosociality and over time led to the acquisition of an individual's third person perspective. The entangled biological evolution accelerated the ongoing cumulative cultural evolution by selecting traits facilitating social transmission. In this context, tool evolution and the corresponding acquired individual instructional content is a precondition to the emergence of higher cognition and "consciousness." A neuroscience investigating externalizations as the starting point of this process is urgently needed.