Search Results (407)

New psychoactive substances (NPSs) have emerged as a significant global public health challenge due to their ability to mimic traditional drugs. Among these, mephedrone has gained attention because of its widespread use and associated toxicities. This review provides a comprehensive analysis of the structure, pharmacokinetic properties, and metabolic pathways of mephedrone, highlighting its phase I and phase II metabolites as potential biomarkers for detection and forensic applications. A comprehensive literature search was performed without date restrictions. The search employed key terms such as “mephedrone metabolites”, “pharmacokinetics of mephedrone”, “phase I metabolites of mephedrone”, and “phase II metabolites of mephedrone”. Additionally, the reference lists of selected studies were screened to ensure a thorough review of the literature. Mephedrone is a chiral compound existing in two enantiomeric forms, exhibiting different affinities for monoamine transporters and distinct pharmacological profiles. In vivo animal studies indicate rapid absorption, significant tissue distribution, and the formation of multiple phase I metabolites (e.g., normephedrone, dihydromephedrone, 4-carboxymephedrone) that influence its neurochemical effects. Phase II metabolism involves conjugation reactions leading to metabolites such as N-succinyl-normephedrone and N-glutaryl-normephedrone, further complicating its metabolic profile. These findings underscore the importance of elucidating mephedrone’s metabolic pathways to improve detection methods, enhance our understanding of its toxicological risks, and inform future therapeutic strategies. Full article

Degenerative disc disease (DDD) is a major cause of chronic low back pain (LBP), yet the molecular mechanisms driving disc degeneration and pain remain poorly understood. This study analyzed intervertebral disc (IVD) tissue from 36 young patients (median age = 36.00 [31.00, 42.50] years) with herniated discs and LBP, alongside healthy controls, to investigate changes in the extracellular matrix (ECM) and neurochemical alterations. Disc degeneration was assessed using MRI (Pfirrmann grading) and histology (Sive’s criteria). Histochemical and immunohistochemical methods were used to evaluate aggrecan content, calcification, and the expression of nerve growth factor (NGF), substance P (SP), and S-100 protein. MRI findings included Pfirrmann grades V (30.55%), IV (61.11%), III (5.56%), and II (2.78%). Severe histological degeneration (10–12 points) was observed in three patients. Aggrecan depletion correlated with longer pain duration (r = 0.449, p = 0.031). NGF expression was significantly elevated in degenerated discs (p = 0.0287) and strongly correlated with SP (r = 0.785, p = 5.268 × 10⁻⁹). Free nerve endings were identified in 5 cases. ECM calcification, present in 36.1% of patients, was significantly associated with radiculopathy (r = 0.664, p = 0.005). The observed co-localization of NGF and SP suggests a synergistic role in pain development. These results indicate that in young individuals, aggrecan loss, neurochemical imbalance, and ECM calcification are key contributors to DDD and chronic LBP. Full article

Heavy metals are a major toxicological concern due to their adverse effects on human health, particularly in children exposed to contaminated areas. This study evaluated biomarkers of exposure in 253 children aged 6 to 12 from Magangue, Achi, and Arjona (Bolivar, Colombia), analyzing their relationship with neurotoxicity and hematological markers. The mean Pb concentrations at the study sites were 1.98 µg/g (Magangue) > 1.51 µg/g (Achi) > 1.24 µg/g (Arjona). A similar pattern was observed for Cd concentrations for Magangue (0.39 µg/g) > Achi (0.36 µg/g) > Arjona (0.14 µg/g). In contrast, Se concentrations followed a different trend for Arjona (0.29 µg/g) > Magangue (0.21 µg/g) > Achi (0.16 µg/g). The proportion of Se/Pb molar ratios > 1 was higher in Arjona (3.8%) than in Magangue (0.9%) and Achi (2.0%). For Se/Cd ratios, values > 1 were also more frequent in Arjona (70.7%), exceeding 20% in the other two locations. Significant differences were found among locations in red and white blood cell parameters and platelet indices. Neurotransmitter-related biomarkers, including serotonin, monoamine oxidase A (MAO-A), and acetylcholinesterase levels, also varied by location. Principal component analysis showed that Pb and Cd had high loadings on the same component as PLT, WBC, and RDW, and while Se loaded together with HGB, PDW, MCHC, MCH, and MCV, suggesting distinct hematological patterns associated with each element. Multiple linear regression analysis demonstrated a statistically significant inverse association between hair Pb levels and serotonin concentrations. Although MAO-A and Cd showed negative β coefficients, these associations were not statistically significant after adjustment. These findings highlight the potential impact of toxic element exposure on key hematological and neurochemical parameters in children, suggesting early biological alterations that may compromise health and neurodevelopment. Full article

Clinical and animal studies suggest that multiple brain systems are involved in mediating reward-motivated and related emotional behavior including the consumption of commonly used drugs and palatable food, and there is evidence that the repeated ingestion of or exposure to these rewarding substances may in turn stimulate these brain systems to produce an overconsumption of these substances along with co-occurring emotional disturbances. To understand this positive feedback loop, this review focuses on a specific population of hypothalamic peptide neurons expressing melanin-concentrating hormone (MCH), which are positively related to dopamine reward and project to forebrain areas that mediate this behavior. It also examines neurons expressing the peptide hypocretin/orexin (HCRT) that are anatomically and functionally linked to MCH neurons and the molecular systems within these peptide neurons that stimulate their development and ultimately affect behavior. This report first describes evidence in animals that exposure in adults and during adolescence to rewarding substances, such as the drugs alcohol, nicotine and cocaine and palatable fat-rich food, stimulates the expression of MCH as well as HCRT and their intracellular molecular systems. It also increases reward-seeking and emotional behavior, leading to excess consumption and abuse of these substances and neurological conditions, completing this positive feedback loop. Next, this review focuses on the model involving embryonic exposure to these rewarding substances. In addition to revealing a similar positive feedback circuit, this model greatly advances our understanding of the diverse changes that occur in these neuropeptide/molecular systems in the embryo and how they relate, perhaps causally, to the disturbances in behavior early in life that predict a later increased risk of developing substance use disorders. Studies using this model demonstrate in animals that embryonic exposure to these rewarding substances, in addition to stimulating the expression of peptide neurons, increases the intracellular molecular systems in neuroprogenitor cells that promote their development. It also alters the morphology, migration, location and neurochemical profile of the peptide neurons and causes them to develop aberrant neuronal projections to forebrain structures. Moreover, it produces disturbances in behavior at a young age, which are sex-dependent and occur in females more than in males, that can be directly linked to the neuropeptide/molecular changes in the embryo and predict the development of behavioral disorders later in life. These results supporting the close relationship between the brain and behavior are consistent with clinical studies, showing females to be more vulnerable than males to developing substance use disorders with co-occurring emotional conditions and female offspring to respond more adversely than male offspring to prenatal exposure to rewarding substances. It is concluded that the continued consumption of or exposure to rewarding substances at any stage of life can, through such peptide brain systems, significantly increase an individual’s vulnerability to developing neurological disorders such as substance use disorders, anxiety, depression, or cognitive impairments. Full article

Background: Anabolic–androgenic steroids (AASs) are commonly used for performance enhancement but have been linked to significant neurobiological consequences. This review explores the impact of AASs on neurochemical pathways, cognitive function, and psychiatric disorders, highlighting their potential neurotoxicity. Methods: A narrative review of current literature was conducted to examine AASs-induced alterations in neurotransmitter systems, structural and functional brain changes, and associated psychiatric conditions. The interplay between AASs use and other substances was also considered. Results: Chronic AASs exposure affects serotonin and dopamine systems, contributing to mood disorders, aggression, and cognitive deficits. Structural and functional changes in the prefrontal cortex and limbic regions suggest long-term neurotoxicity. AASs use is associated with increased risks of depression, anxiety, and psychosis, potentially driven by hormonal dysregulation and neuroinflammation. Co-occurring substance use exacerbates neurocognitive impairments and behavioral disturbances. Discussion: While evidence supports the link between AASs use and neurotoxicity, gaps remain in understanding the precise mechanisms and long-term effects. Identifying biomarkers of brain damage and developing targeted interventions are crucial for mitigating risks. Increased awareness among medical professionals and policymakers is essential to address AASs-related neuropsychiatric consequences. Conclusions: AASs abuse poses significant risks to brain health, necessitating further research and prevention efforts. Evidence-based strategies are needed to educate the public, enhance early detection, and develop effective interventions to reduce the neuropsychiatric burden of AASs use. Full article

Serotoninomics is an expanding field that focuses on the comprehensive study of the serotoninergic system, including serotonin’s biosynthesis, metabolism, and regulation, as well as related scientific methodologies 5-hydroxytryptamine (5-HT). This field explores serotonin’s complex roles in various physiological and pathological contexts. The essential amino acid tryptophan (Trp) is a precursor for several metabolic and catabolic pathways, with the kynurenine (KYN) pathway being particularly significant, representing about 95% of Trp metabolism. In contrast, only a small portion (1–2%) of dietary Trp enters the serotonin pathway. Anthranilic acid (AA), a metabolite in the KYN pathway, has emerged as a potential biomarker and therapeutic target for schizophrenia. Elevated serum AA levels in patients with schizophrenia have been associated with neurotoxic effects and disruptions in neurotransmission, suggesting AA’s critical role in the disorder’s pathophysiology. Furthermore, the 5-HT_2A receptor’s involvement is particularly noteworthy, especially in relation to schizophrenia’s positive symptoms. Recent findings indicate that 5-HT_2A receptor hyperactivity is linked to positive symptoms of schizophrenia, such as hallucinations and delusions. This study investigates serotoninomics’ implications for neuropsychiatric disorders, focusing on AA in schizophrenia and analysing recent research on serotonin signalling pathways and AA’s neurochemical effects. Understanding the roles of the 5-HT_2A receptor and AA in neuropsychiatric disorders could lead to the development of more precise and less invasive diagnostic tools, specific therapeutic strategies, and improved clinical outcomes. Ongoing research is essential to uncover these pathways’ exact mechanisms and therapeutic potential, thereby advancing personalised medicine and innovative treatments in neuropsychiatry. Full article

In the last several decades, a number of animal models of neurological diseases have been proposed and validated to one degree or another. This review focuses on the olfactory bulbectomized rodent as a model of major depression, a disorder that, because of its prevalence, has been called the “common cold” of neurological diseases, though the disability it causes is far more profound. After describing the method, a brief history of this model and the various validity claims made for it are discussed. Though a legion of physiological and biochemical sequelae of bulbectomy and other animal models of depression have been reported, the focus of this review is behavioral. Therefore, the neurochemical and molecular aspects of the depression models mentioned in this review will not be explored in depth. Lastly, unresolved questions posed by the bulbectomy model are considered along with its utility in the study of other neurological diseases and its future prospects. Full article

Borderline personality disorder (BPD) is a complex and heterogeneous condition characterized by emotional instability, impulsivity, and impaired regulation of interpersonal relationships. This narrative review integrates findings from recent neuroimaging, neurochemical, and treatment studies to identify core neurobiological mechanisms and highlight translational potential. Evidence from 112 studies published up to 2025 is synthesized, encompassing structural MRI, resting-state and task-based functional MRI, EEG, PET, and emerging machine learning applications. Consistent disruptions are observed across the prefrontal–amygdala circuitry, the default mode network (DMN), and mentalization-related regions. BPD shows a dominant and stable pattern of hyperconnectivity in the precuneus. Transdiagnostic comparisons with PTSD and cocaine use disorder (CUD) suggest partial overlap in DMN dysregulation, though BPD-specific traits emerge in network topology. Machine learning models achieve a classification accuracy of 70–88% and may support the tracking of early treatment responses. Longitudinal fMRI studies indicate that psychodynamic therapy facilitates the progressive normalization of dorsal anterior cingulate cortex (dACC) activity and reductions in alexithymia. We discuss the role of phenotypic heterogeneity (internalizing versus externalizing profiles), the potential of neuromodulation guided by biomarkers, and the need for standardized imaging protocols. Limitations include small sample sizes, a lack of effective connectivity analyses, and minimal multicenter cohort representation. Future research should focus on constructing multimodal biomarker panels that integrate functional connectivity, epigenetics, and computational phenotyping. This review supports the use of a precision psychiatry approach for BPD by aligning neuroscience with scalable clinical tools. Full article

Background/Objectives: There is evidence concerning herbal medicines and plant-based compounds, including Lamiaceae species, as putative senolytic agents; however, there are only a few reports on Ocimum americanum properties using rat models. The aim of this study was to investigate the neuroprotective effects and potential modes of action of Ocimum americanum L. using ex vivo and in vivo assays to assess the effects of OAEE on hippocampal tissue from young adult and late middle-aged Wistar rats, with a focus on oxidative stress, cholinesterase activity, and neuroinflammatory markers. Methods: Ocimum americanum ethanol extract (OAEE) was incubated with hippocampal slices of young adult and late middle-aged male Wistar rats exposed to H₂O₂; an acute treatment with OAEE was evaluated in aversive memory performance and neurochemical parameters, such as hippocampal cellular oxidative state, and anticholinesterase activity, and a diet supplementation of OAEE were evaluated on several hippocampal biochemical parameters, such as oxidative state, anticholinesterase activity, and neuroinflammatory parameters in young adult and late middle-aged male rats. Results: OAEE reversed the H₂O₂-induced impaired cellular viability in hippocampal slices from young adult rats, as well as protected hippocampal slices against H₂O₂-induced damage in both young adult and late middle-aged Wistar rats, indicating its neuroprotective action. Chronic dietary OAEE supplementation reduced aging-induced increases in reactive species and lipid peroxidation levels in the hippocampus. Indeed, this supplementation reduced the TNF-α content in hippocampus from both ages, and IL-1β levels in young adult rats. Conclusions: The antioxidant actions of OAEE here observed, preventing the lipoperoxidation, as well as its anti-neuroinflammatory effect, might be related to neuroprotective effect. Our findings add evidence to support the idea of the potential use of Ocimum americanum as a nutraceutical or functional food in the aging process. Full article

Schizophrenia is a complex psychiatric disorder traditionally linked to neurotransmitter dysregulation, particularly within dopamine and glutamate pathways. However, recent evidence implicates the gut–brain axis as a potential contributor to its pathophysiology. This perspective article proposes a systems-level understanding of schizophrenia that incorporates the role of gut microbial dysbiosis specifically, reductions in short-chain fatty acid (SCFA)-producing taxa, and elevations in pro-inflammatory microbes. These imbalances may compromise gut barrier integrity, stimulate systemic inflammation, and disrupt neurochemical signaling in the brain. We synthesize findings from animal models, clinical cohorts, and microbial intervention trials, highlighting mechanisms such as SCFA regulation, altered tryptophan–kynurenine metabolism, and microbial impacts on neurotransmitters. We also explore microbiome-targeted interventions like probiotics, prebiotics, dietary strategies, and fecal microbiota transplantation (FMT) and their potential as adjunctive therapies. While challenges remain in causality and translation, integrating gut–brain axis insights may support more personalized and biologically informed models of schizophrenia care. Full article

Background: This study aimed to compare the immediate effects of small-sided games (SSGs) and running-based high-intensity interval training (HIITrb) on serum brain-derived neurotrophic factor (BDNF) levels, cognitive performance, and enjoyment in young, male soccer players. Methods: Twenty-four soccer players [age: 19.2 ± 0.8 years] completed one session each of four-a-side SSG or HIITrb in a randomized, counterbalanced, and crossover design, with a one-week washout period. Blood samples and Trail Making Tests (TMTs) A and B were measured before and after exercise. Heart rate (HR) was monitored throughout the games, and ratings of perceived exertion (RPE) and enjoyment were collected at the end of the measurements. Results: The results show no significant effects of time (p > 0.775), group (p > 0.276) or time × group interaction (p > 0.199) on BDNF levels. For TMT-A, the time effect (p = 0.866) and group effect (p = 0.057) were not significant; however, the time × group interaction was significant (p < 0.019), indicating a superior performance in the SSG compared to HIITrb. In the TMT-B, significant effects were observed for both time (p < 0.001) and group (p < 0.001), while the time × group interaction effect was not statistically significant (p > 0.061). Furthermore, enjoyment levels did not differ significantly between conditions (p = 0.976). Conclusions: These findings suggest that four-a-side SSG may enhance processing speed compared to HIITrb without changes in serum BDNF levels. Coaches may consider using 4v4 SSG formats in early training sessions or warm-ups to stimulate processing speed and mental readiness in young soccer players. Full article

Zebrafish (Danio rerio) combine accessible behavioral phenotypes with conserved neurochemical pathways and molecular features of vertebrate brain function, positioning them as a powerful model for investigating early neurodegenerative processes and screening neuroprotective strategies. In this context, integrated behavioral and proteomic analyses provide valuable insights into the initial pathophysiological events shared by conditions such as Parkinson’s disease and related disorders—including mitochondrial dysfunction, oxidative stress, and synaptic impairment—which emerge before overt neuronal loss and offer a crucial window to understand disease progression and evaluate therapeutic candidates prior to irreversible damage. To investigate this early window of dysfunction, zebrafish larvae were exposed to 500 μM 1-methyl-4-phenylpyridinium (MPP⁺) from 1 to 5 days post-fertilization and evaluated through integrated behavioral and label-free proteomic analyses. MPP⁺-treated larvae exhibited hypokinesia, characterized by significantly reduced total distance traveled, fewer movement bursts, prolonged immobility, and a near-complete absence of light-evoked responses—mirroring features of early Parkinsonian-like motor dysfunction. Label-free proteomic profiling revealed 40 differentially expressed proteins related to mitochondrial metabolism, redox regulation, proteasomal activity, and synaptic organization. Enrichment analysis indicated broad molecular alterations, including pathways such as mitochondrial translation and vesicle-mediated transport. A focused subset of Parkinsonism-related proteins—such as DJ-1 (PARK7), succinate dehydrogenase (SDHA), and multiple 26S proteasome subunits—exhibited coordinated dysregulation, as visualized through protein–protein interaction mapping. The upregulation of proteasome components and antioxidant proteins suggests an early-stage stress response, while the downregulation of mitochondrial enzymes and synaptic regulators reflects canonical PD-related neurodegeneration. Together, these findings provide a comprehensive functional and molecular characterization of MPP⁺-induced neurotoxicity in zebrafish larvae, supporting its use as a relevant in vivo system to investigate early-stage Parkinson’s disease mechanisms and shared neurodegenerative pathways, as well as for screening candidate therapeutics in a developmentally responsive context. Full article

Experiences of life-threatening stimuli can induce post-traumatic stress disorder (PTSD), which is associated with long-lasting behavioral and neurochemical abnormalities. Despite its increased global incidence, the current treatment options for PTSD remain limited, highlighting the need for novel therapeutic strategies. As oxidative stress and neuroinflammation contribute to PTSD, the use of powerful antioxidants such as thiamine (B1 vitamin) compounds may counteract disease development. Young C57BL/6 mice received thiamine or benfotiamine in drinking water (each at a dose of 200 mg/kg/day) for 21 days, and for the last five days, they were subjected to rat exposure. Mice were studied for anxiety-like behavior, exploration, locomotion, grooming, social interactions, pain sensitivity, brain changes in protein carbonyl (PC), total glutathione (TG), and gene expression of distress and inflammation markers. Rat exposure induced anxiety-like behavior, excessive grooming, and alteration in locomotion, along with other abnormalities. Stressed, untreated mice had elevated levels of PC and TG in the prefrontal cortex, hippocampus, amygdala, and striatum and increased expression of Il-1β, Tnf, c-Fos, Cox-1, and Cox-2. Treatment with thiamine or benfotiamine significantly ameliorated most of these changes in the stressed groups. Thus, thiamine compounds may have therapeutic potential in patients with PTSD, owing to their antioxidant and anti-inflammatory properties. Full article

The rapid advancement of flexible sensor technology has profoundly transformed neural interface research, enabling multimodal information acquisition, real-time neurochemical and electrophysiological signal monitoring, and adaptive closed-loop regulation. This review systematically summarizes recent developments in flexible materials and microstructural designs optimized for enhanced biocompatibility, mechanical compliance, and sensing performance. We highlight the progress in integrated sensing systems capable of simultaneously capturing electrophysiological, mechanical, and neurochemical signals. The integration of carbon-based nanomaterials, metallic composites, and conductive polymers with innovative structural engineering is analyzed, emphasizing their potential in overcoming traditional rigid interface limitations. Furthermore, strategies for multimodal signal fusion, including electrochemical, optical, and mechanical co-sensing, are discussed in depth. Finally, we explore future perspectives involving the convergence of machine learning, miniaturized power systems, and intelligent responsive materials, aiming at the translation of flexible neural interfaces from laboratory research to practical clinical interventions and therapeutic applications. Full article

Background/Objectives: Major depressive disorder (MDD) is a debilitating illness, and chronic stress is a contributing factor for depressive symptoms. However, despite intense research, the mechanisms of MDD remain substantially unidentified. Quercetin is a powerful flavonoid and could be used as a possible therapeutic strategy for depression. Acknowledging the potential benefits of quercetin, this study investigated its effect alone or in association with the standard drug tranylcypromine (TCP) in a rodent model of chronic restraint stress (CRS). Methods: Adult male rats were subjected to a CRS model consisting of an immobilization session of 4 h daily during 14 consecutive days. Quercetin (50 mg/kg, gavage) was administered for 45 days. TCP (10 mg/kg, gavage) was administered for 14 days. Behavioral tasks were conducted to assess locomotor functions, memory, anhedonia, depression-like behaviors, and anxiety-like behaviors. The activity, gene expression, and protein density of acetylcholinesterase (AChE) were investigated. Results: Behavioral tasks showed that the CRS model effectively induced stable behavioral changes. CRS did not alter locomotor function assessed by the open field test (OFT) or anhedonia behavior assessed by the sucrose preference test (SPT). CRS increased total fecal count, which was prevented by quercetin administration in rats. TCP and the association of quercetin and TCP increased the recognition index in comparison with the CRS group in the novel object recognition (NOR) test and improved the swimming and immobility times in comparison to stressed animals in the forced swim test (FST). All treatments were able to decrease the anxiety index assessed by the elevated plus maze (EPM) test. The activity, gene expression, and protein density of AChE were increased in the CRS model compared to control males. Overall, quercetin and TCP proved to reverse CRS-induced alterations in these parameters. Conclusions: Quercetin mitigated cognitive deficits, behavioral impairments, and neurochemical alterations induced by the CRS model, especially in association with TCP, supporting its potential as a promising therapeutic agent for depression. Full article