Search Results (575)

Striatum can be described as a brain region containing a general neuronal mechanism to associate actions or events with reward. In particular, neural activity in the human striatum is modulated by social actions and, critically, by the conjunction of social actions and own reward. To perform this function, dopamine and oxytocin signaling reaching the striatum represent a key factor. These neurotransmitters, in both humans and animals, are released in response to afferent vagal and sensory stimulation, as well as sexual and social interactions, conveying information related to reward and pleasure associated with an event. Dopamine and oxytocin have several effects in common, but of particular interest is evidence indicating that they can mutually modulate their action. The present review focuses on available data delineating interactions between dopaminergic and oxytocinergic signaling in the striatum. In this context, recent data on the possible role played by striatal astrocytes and microglia as key modulators of this crosstalk will be briefly discussed. Full article

The gut–brain axis refers to the bidirectional communication network linking the gut microbiota and the central nervous system (CNS). Recent research has highlighted the critical role of gut microbiota in influencing brain health, neurogenesis, and neuroinflammation. In the context of brain tumors, especially gliomas, the gut–brain axis plays a significant role in tumor development, progression, and response to therapy. Gut dysbiosis, characterized by an imbalance in microbiota composition, has been linked to chronic inflammation, immune suppression, and altered blood–brain barrier (BBB) permeability, key factors in glioma pathogenesis. Gut-derived metabolites such as short-chain fatty acids (SCFAs) and neurotransmitters can either promote or inhibit tumor growth, impacting the tumor microenvironment (TME) and immune responses. Emerging evidence suggests that microbiome modulation, through strategies such as probiotics, prebiotics, and dietary interventions, may enhance anti-tumor immunity and improve the efficacy of conventional treatments like chemotherapy, radiotherapy, and immunotherapy. This review examines the interactions between gut microbiota and brain tumors, focusing on how microbiota alterations may influence tumor biology and therapeutic outcomes. Understanding the mechanisms of the gut–brain axis could lead to novel adjunctive therapies in neuro-oncology, offering new prospects for personalized treatment strategies in brain tumor management. Full article

Peripartum depression (PPD) represents a significant public health concern, affecting 10–17% of women globally. Traditional monoaminergic treatments demonstrate limited efficacy and delayed onset of action. The glutamate–GABA imbalance hypothesis provides a novel theoretical framework for understanding depression pathophysiology and developing targeted therapeutic interventions. This review examines emerging pharmacotherapeutic approaches targeting glutamatergic and GABAergic neurotransmitter systems for PPD treatment. Search criteria targeted randomized clinical trials investigating GABA-A-positive allosteric modulators (brexanolone, zuranolone, and ganaxolone) and NMDA receptor antagonists (ketamine and esketamine) in PPD patients. Brexanolone was the first neurosteroid to receive FDA approval for PPD, while zuranolone also shows promise. Ketamine and esketamine are also associated with reduced PPD risk, particularly with perioperative administration during cesarean delivery, though benefits are predominantly short-term. These glutamate–GABA pathway modulators represent novel therapeutic alternatives with rapid onset profiles. Further investigation and research are needed to optimize dosing protocols and patient selection criteria and to establish long-term efficacy before PPD treatment guidelines can be drafted. Full article

N-acetylcysteine (NAC) has garnered increasing interest for its neurotherapeutic capabilities beyond its recognized functions as a mucolytic agent and an antidote for acetaminophen toxicity. This review consolidates findings from both preclinical and clinical studies to investigate NAC’s diverse modulatory effects on the central nervous system (CNS). NAC primarily functions as an antioxidant by replenishing glutathione and mitigating oxidative stress; however, it produces glutathione-independent effects through the modulation of mitochondrial redox systems, ferroptosis, and the Nrf2-ARE signaling pathway. It plays a significant role in neuroinflammatory processes by inhibiting the production of cytokines, the expression of iNOS, and the activation of microglia. Furthermore, NAC affects various neurotransmitter systems—including glutamatergic, dopaminergic, GABAergic, serotonergic, cholinergic, and adrenergic pathways—by modulating synaptic transmission, receptor activity, and transporter functionality. It promotes neuroprotection through the enhancement of neurotrophic factors, the preservation of mitochondrial integrity, and the upregulation of survival signaling pathways. Recent evidence also emphasizes NAC’s role in gene expression and the regulation of cortisol levels. The extensive range of NAC’s neurobiological effects highlights its therapeutic potential in treating neurodegenerative and neuropsychiatric disorders. Nevertheless, the variability in clinical outcomes indicates a pressing need for more focused, mechanism-based research. Full article

Background and Objectives: Methamphetamine (METH) is a potent psychostimulant known to induce neurotoxicity and neurodegeneration, leading to cognitive impairment. This study aimed to explore cubebin’s potential neuroprotective effects against METH-induced cognitive deficits by investigating its ability to suppress lipid peroxidation and pro-inflammatory markers and modulate neurotransmitter levels. Material and Methods: A total of 30 rats were taken and randomly grouped into five groups: group I—control; group II—METH 100 mg/kg/i.p.; group III—METH + cubebin (10 mg/kg/p.o.); group IV—METH + cubebin (20 mg/kg/p.o.); and group V—cubebin per os at 20 mg/kg. After a 14-day oral regimen, behavioral activities were assessed utilizing the Morris water maze (MWM). Biochemical analysis included neurotransmitters, including dopamine (DA), norepinephrine (NE), and gamma-aminobutyric acid (GABA); oxidative stress markers (malondialdehyde (MDA); nitric oxide (NO), catalase (CAT), reduced glutathione (GSH)); inflammatory cytokines [interleukin (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)]; neurotrophic factors (BDNF, CREB); and apoptotic markers (caspase-3 and caspase-9). Furthermore, molecular docking and simulation studies were conducted. Results: Treatment with cubebin led to a marked reduction in latency during the MWM task. It significantly modulated the oxidative stress markers (SOD, GSH, CAT, MDA, and NO), inflammatory cytokines (IL-6, IL-1β, TNF-α), neurotrophic factors (CREB, BDNF), apoptotic markers (NFkB, caspase-3, caspase-9), and neurotransmitters (NE, DA, and GABA) in METH-induced memory-impaired rats. The results of molecular dynamics simulation (MDS) provided insight into the mechanisms that associate proteins CREB, BDNF, and caspase-3 in conformational dynamics upon binding to cubebin. Conclusions: In conclusion, cubebin administration improved cognitive function in rats by modulating antioxidant enzyme activity, reducing pro-inflammatory cytokines, and regulating neurotransmitter levels, demonstrating its potential neuroprotective effects against MA-induced neurodegeneration. Full article

Background: Glaucoma is a progressive optic neuropathy marked by retinal ganglion cells (RGCs), apoptosis, vascular insufficiency, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. While intraocular pressure (IOP) reduction remains the primary intervention, many patients continue to lose vision despite adequate pressure control. Emerging neuroprotective agents—citicoline, coenzyme Q10 (CoQ10), pyruvate, nicotinamide, pyrroloquinoline quinone (PQQ), homotaurine, berberine, and gamma-aminobutyric acid (GABA)—target complementary pathogenic pathways in experimental and clinical settings. Methods: This literature review synthesizes current evidence on glaucoma neuroprotection, specifically drawing on the most relevant and recent studies identified via PubMed. Results: Citicoline enhances phospholipid synthesis, stabilizes mitochondrial membranes, modulates neurotransmitters, and improves electrophysiological and visual field outcomes. CoQ10 preserves mitochondrial bioenergetics, scavenges reactive oxygen species, and mitigates glutamate-induced excitotoxicity. Pyruvate supports energy metabolism, scavenges reactive oxygen species, and restores metabolic transporter expression. Nicotinamide and its precursor nicotinamide riboside boost NAD⁺ levels, protect against early mitochondrial dysfunction, and enhance photopic negative response amplitudes. PQQ reduces systemic inflammation and enhances mitochondrial metabolites, while homotaurine modulates GABAergic signaling and inhibits β-amyloid aggregation. Berberine attenuates excitotoxicity, inflammation, and apoptosis via the P2X7 and GABA-PKC-α pathways. Preclinical models demonstrate synergy when agents are combined to address multiple targets. Clinical trials of fixed-dose combinations—such as citicoline + CoQ10 ± vitamin B3, citicoline + homotaurine ± vitamin E or PQQ, and nicotinamide + pyruvate—show additive improvements in RGCs’ electrophysiology, visual function, contrast sensitivity, and quality of life without altering IOP. Conclusions: A multi-targeted approach is suitable for glaucoma’s complex neurobiology and may slow progression more effectively than monotherapies. Ongoing randomized controlled trials are essential to establish optimal compound ratios, dosages, long-term safety, and structural outcomes. However, current evidence remains limited by small sample sizes, heterogeneous study designs, and a lack of long-term real-world data. Integrating combination neuroprotection into standard care holds promise for preserving vision and reducing the global burden of irreversible glaucoma-related blindness. Full article

Background: Essence of chicken (EC) has been found to improve brain function, increase short-term working memory, and reduce fatigue. However, the specific bioactives after EC consumption remain unknown, and the effect of EC on sleep deprivation (SD) is also elusive. The aim of the present study is to clarify the metabolic changes induced by EC supplementation in the serum and brain and identify characteristic bioactive metabolites significantly altered after EC consumption. Methods: Firstly, a kinetic analysis of EC consumption was performed to determine the time-sequential change in serum and brain metabolites in mice using gas chromatography coupled with mass spectrometry (GC/MS). Next, the impact of EC on the metabolic signatures in an acute SD mouse model was assessed. Results: Based on the results of the kinetic study, myristoleic acid and L-tyrosine were significantly increased in the serum, whereas gentisic acid was significantly increased in the brain after the administration of EC. In addition, EC administration differentially modulated SD-induced alterations in gene expression across brain regions of acute sleep-deprived mice, ameliorated abnormal neurotransmitters, and increased several specific metabolites in the serum. Conclusions: These results suggest that EC might be an effective nutritional supplement to alleviate SD-induced physiological changes. Full article

Chronic pain is a complex and persistent condition involving sustained nociceptive input, maladaptive neuroplastic changes, and neuroimmune interactions. Central to its pathophysiology is the dysregulation of neuromodulatory signaling pathways, including neurotransmitters (e.g., dopamine, serotonin, norepinephrine), neuropeptides (e.g., substance P, CGRP), and neurotrophic factors (e.g., BDNF), which modulate both central and peripheral sensitization mechanisms. In disorders such as fibromyalgia, altered monoaminergic transmission has been implicated in the attenuation of descending inhibitory control, thereby enhancing pain perception and reducing responsiveness to conventional therapies. Concurrently, neuroinflammation, driven by glial cell activation and cytokine release, further exacerbates neuronal excitability and reinforces maladaptive signaling loops. Recent technological advances, including transcriptomic profiling, functional neuroimaging, and single-cell RNA sequencing, have provided new insights into patient-specific patterns of neuromodulatory dysfunction, highlighting potential biomarkers for disease stratification and therapeutic targeting. These developments support the hypothesis that dysregulated neuromodulatory circuits not only underlie diverse chronic pain phenotypes but may also serve as intervention points for precision medicine. This narrative review synthesizes current evidence on the roles of neuromodulatory systems in chronic pain, focusing on synaptic plasticity, nociceptor sensitization, and neuroimmune crosstalk. By integrating preclinical findings with clinical observations, we propose a mechanistic framework for understanding pain chronification and guiding future therapeutic strategies. Harnessing neuromodulatory targets, whether pharmacologically or via neuromodulation technologies, could offer more personalized and effective approaches to chronic pain management. Full article

Nelumbo nucifera (lotus) has long been used in traditional medicine across Asia, and its bioactive alkaloids have recently garnered attention for their neuroprotective properties. This review summarizes the current research on the mechanisms by which lotus-derived alkaloids, particularly neferine, nuciferine, liensinine, and isoliensinine, protect neural tissues. These compounds exhibit a wide range of pharmacological activities, including antioxidant and anti-inflammatory effects, regulation of calcium signaling and ion channels, promotion of neurogenesis, and modulation of key neurotransmitter systems, such as dopaminergic, cholinergic, and GABAergic pathways. Notably, they attenuate tau hyperphosphorylation, reduce oxidative stress-induced neuronal apoptosis, and enhance neurotrophic signaling via BDNF-related pathways. While antioxidant and anti-inflammatory actions are the most extensively studied, emerging evidence also highlights their roles in autophagy modulation and mitochondrial protection. Together, these findings suggest that lotus alkaloids are promising candidates for the prevention and treatment of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Further investigation is warranted to explore the synergistic mechanisms and potential clinical applications of these compounds. Full article

Sleep disturbances are linked to metabolic and neurological dysregulation. Moringa oleifera leaves, rich in bioactive compounds, may improve sleep via gut–brain axis modulation. This study investigated the sleep-enhancing effects of fermented Moringa oleifera leaf extract (FM) in mice using metabolomics, gut microbiota analysis, network pharmacology, and molecular docking. A 1:1 combination of Lactobacillus plantarum GDMCC 1.2685 and L. swissii GDMCC 1.791 optimally fermented FM, increasing GABA by 1.67-fold and total amino acids to 46,058.20 ± 845.53 μg/g. FM shortened sleep latency, increased sleep duration, and elevated brain GABA while reducing glutamate (Glu) and Glu/GABA ratios. Hypothalamic metabolomics identified seven sleep-related metabolites, implicating glycerophospholipid, tryptophan, and purine metabolism pathways. FM also reduced Mycobacterium anisopliae (a gut bacterium associated with insomnia) and increased the Firmicutes/Bacteroidetes ratio. Network pharmacology revealed that FM’s effects were mediated via GABA, Glu, and serotonin (5-HT) pathways. These findings demonstrate that FM improves sleep by modulating hypothalamic neurotransmitters and gut microbiota, exerting sedative-hypnotic effects through amino acid, purine, and energy metabolism. Full article

Research on the effects of polyunsaturated fatty acids on children’s sleep has made significant advancements. This study explores the unique pathways through which polyunsaturated fatty acids, particularly docosahexaenoic acid and eicosapentaenoic acid from the n-3 series, influence sleep regulation in children. Neurobiologically, docosahexaenoic acid and eicosapentaenoic acid have been shown to bi-directionally modulate neurotransmitters and circadian rhythms via the gut–brain axis, reshaping gut microbiota and affecting brain signaling. In terms of inflammation and immune regulation, this study is the first to confirm that Maresin1, produced from n-3 fatty acids, can inhibit the activation of specific inflammasomes, thereby mitigating the disruptive effects of pro-inflammatory cytokines on sleep. The analysis of clinical applications indicates that newly developed medium- and long-chain triglyceride formulations rich in docosahexaenoic acid exhibit excellent digestive absorption in infants’ gastrointestinal systems, paving the way for new products designed to enhance infant sleep. However, current research has limitations concerning the precise dosing of docosahexaenoic acid, the representativeness of samples, and the overall rigor of study designs. Mechanistically, polyunsaturated fatty acids may exert their effects through various pathways, including neurobiology, inflammation, immune regulation, and endocrine modulation. In clinical studies, different formulations of fish oil show varying safety profiles and bioavailability. Future research should prioritize high-quality studies to clarify how different doses of polyunsaturated fatty acids affect children’s sleep, assess long-term safety, and investigate interactions with other factors, ultimately providing solid theoretical and practical guidance for improving children’s sleep. Full article

Background: Dopamine (DA) is a critical neurotransmitter that regulates many physiological and behavioral processes. The central dopaminergic system plays a pivotal role in modulating general anesthesia (GA). DA release in the brain is mainly concentrated in the nucleus accumbens (NAc), prefrontal cortex, hypothalamus, and dorsal striatum. Several NAc neuron subtypes are essential for modulating states of consciousness during GA. However, whether NAc DA signal dynamics correlate with different states of consciousness under sevoflurane anesthesia remains to be elucidated. In this study, we measured the dynamic fluctuations of NAc DA levels throughout sevoflurane anesthesia to verify its role. Methods: An intensity-based genetically encoded DA indicator, dLight1.1, was employed to track DA release in the NAc. Fiber photometry combined with electroencephalogram/electromyogram recordings was employed to synchronously track NAc DA signal dynamics across different states of consciousness under sevoflurane anesthesia. Results: Under 2.5% sevoflurane exposure, DA release in the NAc significantly increased during the initial 100 s of sevoflurane induction, which was designated as sevo on-1 (mean ± standard error of the mean [SEM]; baseline vs. sevo on-1, p = 0.0261), and continued to decrease in the subsequent anesthesia maintenance phases (sevo on-1 vs. sevo on-4, p = 0.0070). Following the cessation of sevoflurane administration (with intervals denoted as sevooff), NAc DA gradually returned to baseline levels (sevo on-1 vs. sevo off-1, p = 0.0096; sevo on-1 vs. sevo off-3, p = 0.0490; sevo on-1 vs. sevo off-4, p = 0.0059; sevo on-4 vs. sevo off-4, p = 0.0340; sevo off-1 vs. sevo off-4, p = 0.0451). During the induction phase, NAc DA signal dynamics markedly increased during the pre-loss of consciousness (LOC) period (pre-anesthesia baseline vs. pre-LOC, p = 0.0329) and significantly declined after LOC (pre-LOC vs. post-LOC, p = 0.0094). For the emergence period, NAc DA release exhibited a noticeable increase during the initial period after recovery of consciousness (ROC) (anesthesia baseline vs. post-ROC, p = 0.0103; pre-ROC vs. post-ROC, p = 0.0086). Furthermore, the DA signals peaked rapidly upon the initiation of the burst wave and then gradually attenuated, indicating a positive correlation with the burst wave onset during burst suppression events. Conclusions: Our findings revealed that NAc DA neurotransmitter signal dynamics correlate with different states of consciousness throughout sevoflurane anesthesia. Full article

The gut microbiota influences both energy metabolism and central nervous system (CNS) functions. This influence is mediated by humoral factors, including various metabolites, neurotransmitters, cytokines, and hormones, in addition to neural pathways such as the vagus nerve. Notably, short-chain fatty acids (SCFAs)—comprising acetic, propionic, and butyric acids—merit specific attention. These compounds originate from the anaerobic fermentation of dietary fibers by the gut microbiota. Growing evidence indicates that SCFAs confer beneficial effects on diverse pain conditions. Although previous review articles have summarized animal studies suggesting the possibility that SCFAs can alleviate pathological pain, there are few reviews on the neurophysiological mechanisms by which SCFAs modulate the excitability of nociceptive neurons in the pain pathway under nociceptive and pathological conditions. Extending previous in vitro findings, our laboratory recently conducted in vivo neurophysiological studies using animal models to explore the pain-relieving properties of SCFAs. Our published results demonstrate two significant effects: (i) an intravenous anesthetic action against nociceptive pain and (ii) an anti-inflammatory contribution to chronic pain alleviation. This review synthesizes the current understanding of the mechanisms by which SCFAs modulate pain and explores their contribution to the attenuation of nociceptive and/or pathological pain. Furthermore, we discuss their prospective clinical application Full article

Sleep deprivation (SD) induces cognitive impairment associated with gut microbiota dysbiosis, making it crucial to explore natural remedies targeting the microbiota–gut–brain axis. This study aims to investigate whether Ficus pandurata var. angustifolia W.C. Cheng (a traditional medicine–food plant rich in flavonoids) can mitigate cognitive impairment caused by SD by modulating the gut microbiota. The sleep-deprived mouse model was established using the multiple platform water environment method. This study investigated the effects of F. pandurata var. angustifolia flavonoids (FCFs) via behavioral tests, 16S rRNA sequencing, and biochemical analyses to assess cognitive function, gut microbiota, and related pathways. FCF alleviated SD-induced cognitive deficits, reversed gut microbiota dysbiosis (increased beneficial bacteria like Lactobacillus, reduced harmful ones like Desulfovibrio), promoted short-chain fatty acids production, improved colonic histopathology and intestinal barrier function, reduced serum lipopolysaccharide, inhibited glial cell activation and TLR4/NF-κB signaling, and regulated neurotransmitters. In conclusion, FCF ameliorates SD-induced cognitive impairment through regulating gut microbiota, enhancing intestinal barrier, and suppressing neuroinflammation via the microbiota–gut–brain axis, providing a theoretical basis for its application. Full article

Attention deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder that not only affects attention and behavior but is also intricately linked with sleep disturbances and immune system dysregulation. Recent research highlights that individuals with ADHD frequently experience sleep problems, which in turn exacerbate ADHD symptoms and contribute to cognitive and emotional difficulties. Immunological alterations, including elevated proinflammatory cytokines and hypothalamic–pituitary–adrenal axis dysfunction, have been observed among ADHD patients, suggesting a biological interplay between inflammation, sleep, and neurodevelopment. Genetic and environmental factors further modulate these relationships, influencing the onset and progression of the disorder. Thus, there is a need to find a key connecting such topics and the most vulnerable subjects in order to contribute towards a more personalized approach. This review examines the complex relationships between sleep, immunology, and ADHD, and explores the underlying mechanisms that involve circadian rhythm genes, neuroinflammation, and neurotransmitter imbalances. Our review outlines therapeutic strategies, emphasizing the importance of integrated pharmacological, behavioral, and lifestyle interventions to improve sleep quality, regulate immune responses, and ultimately enhance the overall management of ADHD. Full article