Reviews in the Neurosciences最新文献

Depression is a common mental disorder characterized by a high prevalence and significant adverse effects, making the searching for effective interventions an urgent priority. In recent years, physical activity (PA) has increasingly been recognized as a standard adjunctive treatment for mental disorders owing to its low cost, easy application, and high efficiency. Epidemiological data shows positive preventive and therapeutic effects of PA on mental illnesses such as depression. This article systematically describes the prophylactic and therapeutic effects of PA on depression and its biological basis. A comprehensive literature analysis reveals that PA significantly improves depressive symptoms by upregulating the expression of "exerkines" such as irisin, adiponectin, and BDNF to positively impacting neuropsychiatric conditions. In particular, lactate could also play a critical role in the ameliorating effects of PA on depression due to the findings about protein lactylation as a novel protein post-transcriptional modification. The literature also suggests that in terms of brain structure, PA may improve hippocampal volume, basal ganglia (neostriatum, caudate-crustal nucleus) and PFC density in patients with MDD. In summary, this study elucidates the multifaceted positive effects of PA on depression and its potential biological mechanisms with a particular emphasis on the roles of various exerkines. Future research may further investigate the effects of different types, intensities, and durations of PA on depression, as well as how to better integrate PA interventions into existing treatment strategies to achieve optimal outcomes in mental health interventions.

Essentially, the blood-brain barrier (BBB) serves as a line of demarcation between neural tissues and the bloodstream. A unique and protective characteristic of the blood-brain barrier is its ability to maintain cerebral homeostasis by regulating the flux of molecules and ions. The inability to uphold proper functioning in any of these constituents leads to the disruption of this specialized multicellular arrangement, consequently fostering neuroinflammation and neurodegeneration. Recent advancements in nanomedicine have been regarded as a promising avenue for improving the delivery of drugs to the central nervous system in the modern era. A major benefit of this innovation is that it allows drugs to accumulate selectively within the cerebral area by circumventing the blood-brain barrier. Although brain-targeted nanomedicines have demonstrated impressive achievements, certain limitations in targeting specificity still exist. In this examination, we scrutinize the distinctive physical and chemical attributes of nanoparticles (NPs) contributing to their facilitation in BBB traversal. We explore the various mechanisms governing NP passage over the BBB, encompassing paracellular conveyance, mediated transport, as well as adsorptive- and receptor-mediated transcytosis. The therapeutic success of NPs for the treatment of brain tumors has been extensively investigated through the use of various categories of NPs. Among these are polymeric nanoparticles, liposomes, solid lipid nanoparticles, dendrimers, metallic nanoparticles, quantum dots, and nanogels. The potential utility of nanoparticles goes beyond their ability to transport pharmaceuticals. They can serve as adept imaging contrast agents, capable of being linked with imaging probes. This will facilitate tumor visualization, delineate lesion boundaries and margins, and monitor drug delivery and treatment response. Versatile nanoparticles can be engineered to effectively target neoplastic lesions, serving dual roles in diagnostic imaging and therapeutic interventions. Subsequently, this discourse explores the constraints associated with nanoparticles in the context of treating brain tumors.

Recently, researchers have been interested in the potential connection between gut microbiota composition and various neuropsychological disorders. Dementia significantly affects the socioeconomics of families. Gut microbiota is considered as a probable factor in its pathogenesis. Multiple bacterial metabolites such as short-chain fatty acids, lipopolysaccharides, and various neurotransmitters that are responsible for the incidence and progression of dementia can be produced by gut microbiota. Various bacterial species such as Bifidobacterium breve, Akkermansia muciniphila, Streptococcus thermophilus, Escherichia coli, Blautia hydrogenotrophica, etc. are implicated in the pathogenesis of dementia. Gut microbiota can be a great target for imitating or inhibiting their metabolites as an adjunctive therapy based on their role in its pathogenesis. Therefore, some diets can prevent or decelerate dementia by altering the gut microbiota composition. Moreover, probiotics can modulate gut microbiota composition by increasing beneficial bacteria and reducing detrimental species. These therapeutic modalities are considered novel methods that are probably safe and effective. They can enhance the efficacy of traditional medications and improve cognitive function.

Cholecystokinin (CCK) is a major neuropeptide in the brain that functions as a neurotransmitter, hormone, and growth factor. The peptide and its receptors are widely expressed in the brain. CCK signaling modulates synaptic plasticity and can improve or impair memory formation, depending on the brain areas studies and the receptor subtype activated. Studies have shown in a series of animal models of neurodegenerative diseases that CCK receptor agonists show neuroprotective effects and can effectively alleviate oxidative stress, alleviate chronic inflammation of the central nervous system, improve neuronal synaptic plasticity, prevent neuronal loss, and improve cognitive dysfunction in Alzheimer's disease (AD) model mice and motor activity in animal models of Parkinson's disease. In addition, CCK plays important roles in the amygdala to regulate anxiety and depressive states. Activation of interneurons or inhibition of excitatory neurons can improve anxiety levels. This review summarizes the effects on memory formation and synaptic plasticity, the neuroprotective effects of cholecystokinin and its analogs in neurological diseases such as Alzheimer and Parkinson's disease, and the effects on anxiety and neuronal activity in the amygdala.

The recognition and classification of facial expressions using artificial intelligence (AI) presents a promising avenue for early detection and monitoring of neurodegenerative disorders. This narrative review critically examines the current state of AI-driven facial expression analysis in the context of neurodegenerative diseases, such as Alzheimer's and Parkinson's. We discuss the potential of AI techniques, including deep learning and computer vision, to accurately interpret and categorize subtle changes in facial expressions associated with these pathological conditions. Furthermore, we explore the role of facial expression recognition as a noninvasive, cost-effective tool for screening, disease progression tracking, and personalized intervention in neurodegenerative disorders. The review also addresses the challenges, ethical considerations, and future prospects of integrating AI-based facial expression analysis into clinical practice for early intervention and improved quality of life for individuals at risk of or affected by neurodegenerative diseases.

Glioblastoma multiforme (GBM) is the most fatal brain tumor with a poor prognosis with current treatments, mainly because of intrinsic resistance processes. GBM is also referred to as grade 4 astrocytoma, that makes up about 15.4 % of brain cancers globally as well as 60-75 % of astrocytoma. The most prevalent therapeutic choices for GBM comprise surgery in combination with radiotherapy and chemotherapy, providing patients with an average survival of 6-14 months. Nanocarriers provide various benefits such as enhanced drug solubility, biocompatibility, targeted activity, as well as minimized side effects. In addition, GBM treatment comes with several challenges such as the presence of the blood-brain barrier (BBB), blood-brain tumor barrier (BBTB), overexpressed efflux pumps, infiltration, invasion, drug resistance, as well as immune escape due to tumor microenvironment (TME) and cancer stem cells (CSC). Recent research has focused on nanocarriers due to their ability to self-assemble, improve bioavailability, provide controlled release, and penetrate the BBB. These nano-based components could potentially enhance drug accumulation in brain tumor tissues and reduce systemic toxicity, making them a compelling solution for GBM therapy. This review captures the complexities associated with multi-functional nano drug delivery systems (NDDS) in crossing the blood-brain barrier (BBB) and targeting cancer cells. In addition, it presents a succinct overview of various types of targeted multi-functional nano drug delivery system (NDDS) which has exhibited promising value for improving drug delivery to the brain.

Stroke is a severe neurological disease and a major worldwide issue, mostly manifesting as ischemic stroke (IS). In order to create effective treatments for IS, it is imperative to fully understand the underlying pathologies, as the existing therapeutic choices are inadequate. Recent investigations have shown the complex relationships between several programmed cell death (PCD) pathways, including necroptosis, ferroptosis, and pyroptosis, and their correlation with immune responses during IS. However, this relationship is still unclear. To address this gap, this review study explored the cellular interactions in the immune microenvironment of IS. Then, to validate prior findings and uncover biomarkers, the study investigated bioinformatics studies. Several pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Toll-like receptor 4 (TLR4), and receptor-interacting protein kinase (RIPK), were involved in PCD-immune interactions. The bioinformatics studies reported key biomarkers such as glutathione peroxidase 4 (GPX4), NOD-like receptor family pyrin domain containing 3 (NLRP3), gasdermin D (GSDMD), and TLR4, which have important implications in ferroptosis, cuproptosis, pyroptosis, and necroptosis respectively. These biomarkers were associated with PCD mechanisms such as oxidative stress and inflammatory reactions. The immune infiltration analysis consistently revealed a significant correlation between PCD pathways and detrimental immune cells, such as neutrophils and γδ T cells. Conversely, M2 macrophages and T helper cells showed protective effects. In conclusion, considering the intricate network of interactions between immune responses and PCD pathways, this study emphasized the necessity of a paradigm shift in therapeutic approaches to address the injuries that are related to this complex network.

Epilepsy is a group of chronic neurological brain disorders characterized by recurrent spontaneous unprovoked seizures, which are accompanied by significant neurobiological, cognitive, and psychosocial impairments. With a global prevalence of approximately 0.5-1 % of the population, epilepsy remains a serious public health concern. Despite the development and widespread use of over 20 anticonvulsant drugs, around 30 % of patients continue to experience drug-resistant seizures, leading to a substantial reduction in quality of life and increased mortality risk. Given the limited efficacy of current treatments, exploring new therapeutic approaches is critically important. In recent years, Gi-protein-coupled receptors, particularly cannabinoid receptors CB1 and CB2, have garnered increasing attention as promising targets for the treatment seizures and prevention of epilepsy. Emerging evidence suggests a significant role of the cannabinoid system in modulating neuronal activity and protecting against hyperexcitability, underscoring the importance of further research in this area. This review provides up-to-date insights into the pathogenesis and treatment of epilepsy, with a special focus on the role of the cannabinoid system, highlighting the need for continued investigation to develop more effective therapeutic strategies.

Vault RNAs (vtRNAs) are a novel group of non-coding RNAs that are involved in various signaling mechanisms. vtRNAs are joined by three proteins major vault protein (MVP), vault poly (ADP-ribose) polymerase (VPARP), and telomerase-associated protein 1 (TEP1) to form the vault complex. In humans, only four vtRNA including vtRNA 1-1, vtRNA 1-2, vtRNA 1-3, vtRNA 2-1) have been discovered. In nerve cells, vtRNA is involved in synapse formation through MAPK signaling. vtRNA travels to the distal area of neurites as a key unit in the vault complex. Moreover, tRNA is detached from the vault complex in the neurite via a mitotic kinase Aurora-A-reliant MVP phosphorylation. Several molecules contribute to the formation of vtRNAs. For instance, SRSF2 and NSUN2 and their attachment to vtRNA1-1 determines the production of small-vtRNAs. Through the same factors, vtRNAs could play a role in neurodevelopmental deficits. Addition the role of vtRNA expression and vault proteins has been recently studied in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) as well as brain cancers. While the mechanisms of vtRNA involvement in neurological disorders is not well-demonstrated, we believe this could be related to the impact of vtRNA regulation in autophagy, immunoregulation, RNA stability, cellular stress, apoptosis, and regulation of other epigenetic pathways. The present review captures the state-of-the-art regarding the role of vtRNAs in neurodevelopment, normal nervous system function, and neurological disorders.

The brain is a highly plastic organ that continually receives and integrates signals to generate functional and structural changes and homeostatic adaptations throughout life. Alterations in some signaling pathways that mediate these responses can impact brain plasticity, accelerate brain aging and potentially lead to neurodegeneration. There is substantial evidence that two important signaling pathways activated by neurotrophins, nonacronymic (VGF) and brain-derived neurotrophic factor (BDNF), are involved in substantial functions stimulating neuronal growth, differentiation, and circuit establishment during development and neuronal maintenance and plasticity in the mature brain. In this review, we present evidence that these two pathways and their interactions are central players in cognitive performance and alterations in pathological aging, particularly in conditions such as Alzheimer's disease (AD). Finally, we suggest specific avenues for future research on the basis of recent findings suggesting these molecules are diagnostic biomarkers and putative therapeutic tools to prevent, delay or improve AD neuropathology.