Central Nervous System Function Research Articles

Environmental Mycotoxins: A Potential Etiological Factor for Neurodegenerative Diseases?

Mycotoxins are potential environmental risk factors for neurodegenerative diseases. These toxins penetrate the central nervous system via a compromised blood-brain barrier, which may cause oxidative stress and neuroinflammation, these can also contribute to amyloid-beta (Aβ) plaque accumulation, Tau protein hyperphosphorylation, and neurofibrillary tangle formation. Mycotoxins also activate microglia, cause neuronal apoptosis, and disrupt central nervous system function. This study examines the evidence linking mycotoxin exposure to neurodegenerative disorders like Alzheimer's and Parkinson's diseases. We explore mechanisms such as oxidative stress, mitochondrial dysfunction, blood-brain barrier disruption, neuroinflammation, and direct neurotoxic effects. Epidemiological studies show regional variations in mycotoxin prevalence and corresponding neurodegenerative disease incidences, supporting this association. We also review current approaches to mitigate mycotoxin exposure and discuss the challenges and opportunities in developing strategies to prevent or slow neurodegenerative disease progression. This work highlights the need for increased awareness and research on mycotoxins as modifiable risk factors in neurological health.

Analysis of the effect of combined rehabilitation training and transcutaneous vagus nerve electrical stimulation on promoting central nervous system remodeling in stroke patients.

To explore the effect of combined rehabilitation training and transcutaneous vagus nerve electrical stimulation (t-VNS) on promoting central nervous system remodeling and neurological function recovery in stroke patients. A total of 124S patients admitted to our hospital from January to December 2023 were included in this study. The therapeutic effects were evaluated using the Modified Barthel Index (MBI) and the simplified Fugl-Meyer Assessment Scale (sFMA) to measure patients' activities of daily living and motor function recovery. Additionally, neurophysiological assessments, including electromyography (EMG) and motor evoked potentials (MEPs), were conducted to evaluate changes in neuromuscular and central nervous system function. Changes in neural activity in the frontal lobe and motor cortex were assessed through transcutaneous vagus nerve stimulation and electroencephalography. Moreover, all adverse events were recorded. After treatment, patients in the t-VNS combined with rehabilitation training group showed significant improvements in sFMA and MBI scores compared to the pure rehabilitation training group (P<0.05). In terms of neurophysiology, patients in the combined treatment group exhibited significant increases in electromyographic activity and MEPs (P<0.05). EEG results indicated enhanced neuroplasticity of the frontal lobe and motor cortex with t-VNS treatment. The incidence of skin stimulation and ear pain in the combined treatment group was significantly higher than that in the pure rehabilitation training group. Combined rehabilitation training and transcutaneous vagus nerve electrical stimulation have significant effects on neurological function recovery and central nervous system remodeling in stroke patients, effectively improving patients' motor function and activities of daily living.

Biomechanical assistance for basketball training movements based on cross-domain EEG physical fitness classification

Cross-domain EEG signals offer valuable insights into the cortical neuron activity patterns and the functional dynamics of the central nervous system (CNS). Within the framework of biomechanics, EEG has emerged as a critical tool to investigate the interplay between neural control and physical performance. This study explores EEG complexity parameters in specific brain regions of 24 elite athletes under three distinct states: Rest, unloaded exercise, and loaded exercise. By integrating biomechanical and electrophysiological analyses, the study uncovers functional adaptations in the parietal and occipital regions, key centers for somatosensory and visual processing, respectively, in high-performance athletes. The findings reveal no significant gender differences in EEG complexity under these conditions, but highlight the effects of long-term specialized training in enhancing CNS adaptability. This adaptation is reflected in a reduced reliance on visual input, a trait distinguishing elite athletes from non-athletes. Despite the small sample size, correlations between three nonlinear EEG parameters—maximum Lyapunov exponent, approximate entropy, and Lempel-Ziv complexity—and CNS fatigue were observed. These parameters provide a robust framework for monitoring CNS fatigue and assessing the effects of exercise on neural function. This study bridges biomechanics and neural analysis, offering a novel perspective on CNS functionality under varying exercise states. The results contribute a theoretical foundation for the development of biomechanical guidance systems tailored for basketball training, with implications for optimizing athletic performance and promoting CNS health.

Critical Review of the Cross-Links Between Dietary Components, the Gut Microbiome, and Depression.

The complex relationship between diet, the gut microbiota, and mental health, particularly depression, has become a focal point of contemporary research. This critical review examines how specific dietary components, such as fiber, proteins, fats, vitamins, minerals, and bioactive compounds, shape the gut microbiome and influence microbial metabolism in order to regulate depressive outcomes. These dietary-induced changes in the gut microbiota can modulate the production of microbial metabolites, which play vital roles in gut-brain communication. The gut-brain axis facilitates this communication through neural, immune, and endocrine pathways. Alterations in microbial metabolites can influence central nervous system (CNS) functions by impacting neuroplasticity, inflammatory responses, and neurotransmitter levels-all of which are linked to the onset and course of depression. This review highlights recent findings linking dietary components with beneficial changes in gut microbiota composition and reduced depressive symptoms. We also explore the challenges of individual variability in responses to dietary interventions and the long-term sustainability of these strategies. The review underscores the necessity for further longitudinal and mechanistic studies to elucidate the precise mechanisms through which diet and gut microbiota interactions can be leveraged to mitigate depression, paving the way for personalized nutritional therapies.

Six weeks that changed the preterm infant brain: lessons learned from the Family Nurture Intervention randomized controlled trials.

We review extensive results from two randomized controlled trials conducted over 9 years, comparing standard care (SC) in level-4 neonatal intensive care units (NICUs) with SC plus Family Nurture Intervention (FNI). FNI included ~six weeks of facilitated mother-infant interactions aimed at achieving mother-infant 'autonomic emotional connection', a novel construct that describes the emotional mother-baby relationship at the level of the autonomic nervous system. Thus far, 18 peer-reviewed publications documented significant positive short-and long-term effects of FNI on infant neurobehavioral functioning, developmental trajectories and both mother and child autonomic health through five years. The observed profound effects of FNI on central and autonomic nervous system function following a relatively short intervention support a novel autonomic theory of emotions. We discuss the theoretical and clinical advances that grew out of the trials and speculate on how FNI changes the mother-infant relationship from 'dysregulation' to autonomic emotional co-regulation. We review new constructs and tools that can be used to view and measure the mother-infant autonomic emotional relationship. We present a simple blueprint to improve preterm birth outcomes. Finally, we discuss the significance of our findings and possible impact on the future of preterm infant care worldwide.

Current Insights into the Neurotoxicity of Melamine: A Comprehensive Review.

Melamine, a heterocyclic nitrogen-rich triazine chemical compound, is widely used in various household products, including furniture, dinnerware, and kitchen appliances. The unauthorized addition of the mixture to various foodstuffs to misrepresent protein content resulted in catastrophic, frequently life-threatening health consequences for kids as well as canines and has garnered international attention. Numerous primary studies and evaluations have been focused on melamine toxicity's implications on kidney function. Despite the profusion of literature on melamine's nephrotoxicity, evidence regarding its toxicity to other organs remains scarce. A number of recent studies suggest melamine can disrupt central nervous system (CNS) function and bring about cognitive impairments, contradicting the commonly held belief that melamine's detrimental effects are limited to the urinary system. The accumulation of melamine in the body is linked to various adverse effects, including depression, impaired synaptic transmission, oxidative stress, and neurodegenerative diseases. Several mechanisms may lead to such complications. However, numerous safeguards against melamine accumulation have been identified. This review could shed light on the potential neurological effects and mechanisms underlying melamine toxicity. Afterward, we will dive into the body's possible protective mechanisms against melamine-induced toxicity.

Localization of Cholecystokinin/Sulfakinin Neuropeptides in Biomphalaria glabrata, an Intermediate Host for Schistosomiasis.

Snails belonging to the genus Biomphalaria serve as obligatory intermediate hosts for the trematode Schistosoma mansoni, the causative agent for the most widespread form of schistosomiasis. The simpler nervous systems of gastropod molluscs, such as Biomphalaria, provide advantageous models for investigating neural responses to infection at the cellular and network levels. The present study examined neuropeptides related to cholecystokinin (CCK), a major multifunctional regulator of central nervous system (CNS) function in mammals. A neural transcriptome generated from the CNS of Biomphalaria alexandrina included a transcript encoding two CCK-related peptides, designated Balex-CCK1 (pEGEWSYDY(SO 3 H)GLGGGRF-NH2) and Balex-CCK2 (NYGDY(SO 3 H)GIGGGRF-NH2). Peptide expression was examined in Biomphalaria glabrata at the mRNA level using the hybridization chain reaction (HCR) protocol and at the protein level using an antibody against Balex-CCK1. Expression was detected in 60-70 neurons distributed throughout the CNS, as well as in profuse fiber systems connecting the ganglia and projecting to the periphery. CCK-like immunoreactive (CCKli) fibers were also observed on organs associated with the cardiorespiratory (nephridium, mantle, gill) and male reproductive systems. A comparison of mRNA and peptide localization suggested that CCK expression could be regulated at the level of translation. A potential role of these peptides in mediating responses to infection by larval schistosomes is discussed.

Parasite infections: how inflammation alters brain function.

Parasitic infections can profoundly impact brain function through inflammation within the central nervous system (CNS). Once viewed as an immune-privileged site, the CNS is now recognized as vulnerable to immune disruptions from both local and systemic infections. Recent studies reveal that certain parasites, such as Toxoplasma gondii and Plasmodium falciparum, can invade the CNS or influence it indirectly by triggering neuroinflammation. These processes may disrupt brain homeostasis, influence neurotransmission, and lead to significant behavioral or cognitive changes. This review discusses the pathways by which parasites disrupt CNS function and highlights systemic inflammation as a critical link between peripheral infections and neuroinflammatory conditions, advancing understanding of parasite-associated neurological complications.

Neurosteroids and Translocator Protein (TSPO) in neuroinflammation.

Neurosteroids have a crucial role in physiological intrinsic regulations of the Central Nervous System functions. They are derived from peripheral steroidogenic sources and from the de novo neurosteroidogenic capacity of brain cells. Significant alterations of neurosteroid levels have been frequently observed in neuroinflammation and neurodegenerative diseases. Such level fluctuations may be useful for both diagnosis and treatment of these pathological conditions. Beyond steroid administration, enhancing the endogenous production by Translocator Protein (TSPO) targeting has been proposed to restore these altered pathological levels. However, the neurosteroid quantification and the prediction of their final effects are often troublesome, sometimes controversial and context dependent, due to the complexity of neurosteroid biosynthetic pathway and to the low produced amounts. The aim of this review is to report recent advances, and technical limitations, in neurosteroid-related strategies against neuroinflammation.

Iron in the migraine brain.

Iron, a vital element for numerous peripheral and central nervous system functions, is a key player in DNA synthesis, gene expression, myelination, neurotransmission, and mitochondrial electron transport. Iron has utmost importance in various neurological functions, including neurotransmitter synthesis and brain cell metabolism. Migraine is a neurogliovascular disorder in which neuroinflammation plays a crucial role. Iron deficiency has been associated with various neurological issues and could potentially influence migraine frequency or severity. However, the relationship between iron levels and migraine is not fully clear and necessitates further research. On the other hand, iron overload could also have negative effects, as excessive iron might contribute to oxidative stress and inflammation, which may impact migraine-related pathways. The interplay between iron levels and neuroinflammation might affect migraines. While iron deficiency could exacerbate inflammation or disrupt neurotransmitter balance, iron overload might increase oxidative stress and neuroinflammation. Comprehending this balance is fundamental, as both iron deficiency and overload can have detrimental effects on brain health and migraine symptoms. In this review, we will summarize the current interconnection between migraine, iron levels, and neuroinflammation that are currently under active investigation.

Nzf2 promotes oligodendrocyte differentiation and regeneration via repressing HDAC1-mediated histone deacetylation.

Proper axonal myelination and function of the vertebrate central nervous system rely largely on the timely differentiation of oligodendrocytes (OLs), yet key regulatory factors remain enigmatic. Our study reveals neural zinc finger (Nzf2) as a crucial orchestrator that controls the timing of OL differentiation both during development and myelin repair, contrasting with its previously suggested role in direct myelin gene regulation. Nzf2 ablation delays the onset of OL differentiation, while hyperactivation stimulates OL differentiation both during development and remyelination. Using RNA-seq and ChIP-seq, we pinpoint Nkx2.2 as a critical downstream target of Nzf2. Specific binding of Nzf2 in the Nkx2.2 gene locus inhibits histone deacetylation by disrupting the HDAC1 repressor complex and reducing deacetylase activity. Furthermore, Nzf2 overrides the inhibitory Notch signaling to initiate OL differentiation. Thus, we propose that the Notch-Nzf2-Nkx2.2 axis is a vital component of OL differentiation timing mechanism, suggesting Nzf2 as a potential therapeutic target for stimulating OL differentiation and boosting myelin repair in demyelinating diseases.

Dipeptides in CSF and plasma: diagnostic and therapeutic potential in neurological diseases

Dipeptides (DPs), composed of two amino acids (AAs), hold significant therapeutic potential but remain underexplored. Given the crucial role of AAs in central nervous system (CNS) function, this study investigated the presence of DPs in cerebrospinal fluid (CSF) and their correlation with corresponding AAs, potentially indicating their role as AA donors. Plasma and CSF samples were collected from 43 children with neurological or metabolic conditions of unknown origin, including 23 with epilepsy. A panel of 33 DPs was quantified using UPLC-MS/MS. Out of 33 DPs, 18 were detectable in CSF and 20 in plasma, displaying high inter-individual variance. Gly-Asp, Gly-Pro, and Ala-Glu were consistently found in all CSF samples, while only Gly-Asp was universally detectable in plasma. Anserine and carnosine were prominent in CSF and plasma, respectively, with no other histidine-containing DPs observed. Generally, DP concentrations were higher in plasma than in CSF; however, anserine and Gly-Pro had similar concentrations in both fluids. Significant correlations were observed between specific DPs and their corresponding AAs in CSF (Gly-Glu, Gly-Pro and Ser-Gln) and plasma (Glu-Glu and Glu-Ser). Notably, patients with epilepsy had elevated medium anserine concentrations in CSF. This study is the first to demonstrate the presence of numerous DPs in CSF and plasma. Further research is needed to determine if DP patterns can support the diagnosis of neurological diseases and whether DP administration can modulate amino acid availability in the brain, potentially offering new therapeutic options, such as for defects in the amino acid transporter.

Microglia balances hypermyelination and demyelination in the brain.

Myelin is crucial for neuron health and central nervous system (CNS) function. Recent research by McNamara etal. highlighted microglia's essential role in compacting the myelin sheath during development and their absence leads to aberrant oligodendrocyte clusters and subsequent cognitive impairment. The study revealed that the critical involvement of the TGFβ1-TGFβR1 axis in microglia-oligodendrocyte communication could influence the oligodendrocyte lipid metabolism and thereby regulate myelin integrity. Further exploration is needed to fully elucidate the dual impact of microglia on myelination, and interactions with other glial cells, holding promise for discovering new targets in myelin-related neurodegenerative and CNS disorders.

Immune Privilege in the Central Nervous System: Implications for Neuroinflammatory Diseases

The central nervous system (CNS) has long been considered an immune-privileged site, where immune responses are tightly regulated to protect neural tissue from inflammation-induced damage. Immune privilege in the CNS is maintained through various mechanisms, including the blood-brain barrier (BBB), the absence of conventional lymphatic drainage, the specialized function of CNS-resident immune cells, and the expression of immunosuppressive molecules like TGF-β and IL-10. These protective systems are essential for preserving CNS homeostasis, as uncontrolled immune activity in the CNS can lead to irreversible damage to neurons and glial cells. However, immune privilege is not absolute. In neuroinflammatory diseases such as multiple sclerosis (MS), neuromyelitis optica (NMO), and Alzheimer’s disease, immune privilege is breached, resulting in the infiltration of immune cells, chronic inflammation, and progressive neural damage. The breakdown of the BBB, immune cell activation, and dysregulated inflammation contribute to the pathophysiology of these diseases. This review examines the mechanisms that underlie immune privilege in the CNS, how these systems are compromised in neuroinflammatory conditions, and the therapeutic implications for modulating immune responses in the CNS. Targeted therapies aimed at restoring immune regulation and preserving CNS function offer promising prospects for treating neuroinflammatory diseases and maintaining CNS health. Keywords: Immune Privilege, Central Nervous System, Neuroinflammatory Diseases, Blood-Brain Barrier, Multiple Sclerosis, Immunosuppressive Mechanisms

Glial polarization in neurological diseases: Molecular mechanisms and therapeutic opportunities.

Glial cell polarization plays a pivotal role in various neurological disorders. In response to distinct stimuli, glial cells undergo polarization to either mitigate neurotoxicity or facilitate neural repair following injury, underscoring the importance of glial phenotypic polarization in modulating central nervous system function. This review presents an overview of glial cell polarization, focusing on astrocytes and microglia. It explores the involvement of glial polarization in neurological diseases such as Alzheimer's disease, Parkinson's disease, stroke, epilepsy, traumatic brain injury, amyotrophic lateral sclerosis, multiple sclerosis and meningoencephalitis. Specifically, it emphasizes the role of glial cell polarization in disease pathogenesis through mechanisms including neuroinflammation, neurodegeneration, calcium signaling dysregulation, synaptic dysfunction and immune response. Additionally, it summarizes various therapeutic strategies including pharmacological treatments, dietary supplements and cell-based therapies, aimed at modulating glial cell polarization to ameliorate brain dysfunction. Future research focused on the spatio-temporal manipulation of glial polarization holds promise for advancing precision diagnosis and treatment of neurological diseases.

Midbrain dopamine drives splenic immunity through a brain-to-body circuit.

Midbrain dopamine neurons are well-known to shape central nervous system function, yet there is growing evidence for their influence on the peripheral immune systems. Here we demonstrate that midbrain dopamine neurons form a circuit to the spleen via a multisynaptic pathway from the dorsal vagal complex (DVC) through the celiac ganglion. Midbrain dopamine neurons modulate the activity of D1-like and D2-like dopamine receptor-expressing DVC neurons. In vivo activation of midbrain dopamine neurons induced dopamine release in the DVC and increased immediate early gene expression in both the DVC and celiac ganglion, indicating enhanced neuronal activity. Activation of this midbrain-to-spleen circuit reduced spleen weight and decreased naïve CD4 + T-cell populations without affecting total T-cell numbers. These findings unveil a functional midbrain-DVC-celiac ganglion-spleen pathway, through which midbrain dopamine neurons modulate splenic immunity. These novel insights into the neural regulation of the immune system have important implications for diseases involving altered dopamine neurotransmission and highlight potential targets for immunotherapeutic interventions.

Features of therapy of localized scleroderma in a severe comorbid patient

Localized scleroderma is an autoimmune chronic connective tissue disease characterized by the appearance of foci of local inflammation in various areas of the skin, followed by the formation of sclerosis and/or atrophy of the skin and underlying tissues in them. Among systemic connective tissue diseases, scleroderma occupies the second place in terms of frequency, mainly female patients. The authors observed a severe comorbid patient S., 75 years old, who was hospitalized at the Federal Center of Brain Research and Neurotechnologies of the FMBA of Russia in the department of medical rehabilitation for patients with impaired central nervous system function № 1 from 02.11.2022 to 03.01.2022 with a diagnosis of the underlying disease: the consequences of an ischemic stroke in the basin of the left middle cerebral artery from 02.23.2021, cardioembolic pathogenetic variant. Right-sided hemiparesis. Complex motor aphasia. After consulting a dermatovenerologist, a diagnosis was added to the concomitant diseases: localized scleroderma. Limited plaque shape. Patient S. external treatment was carried out (fluticasone ointment 0.005 % applied to the affected areas of the skin 1 time a day in a thin layer for 4 weeks), upon discharge, a course of physiotherapy at the place of residence was recommended.

The effects of developmental sub-chronic low-level lead exposure on microglia and a test of possible mitigation by apigenin in C57BL/6/J young mice

Developmental chronic low-level lead (Pb) exposure disrupts central nervous system function and diminishes neurocognition. Microglial cell activation might contribute to these deficits. The present study evaluated the effects of developmental sub-chronic low-level lead exposure on microglial cells and the possible effectiveness of a natural anti-inflammatory intervention with apigenin to mitigate these effects. From PND 0 to 28, 87 C57BL/6 J mice were exposed to one of six treatment conditions: 0 ppm Pb; 30 ppm Pb; 430 ppm Pb; 30 ppm Pb + 400 ppm apigenin; 430 ppm Pb + 400 ppm apigenin; or 400 ppm apigenin, via dam's drinking water. Following sacrifice, brain tissue was harvested and microglial cells were labeled via immunohistochemistry and counted within the dentate gyrus (DG) using unbiased stereology methods. It was hypothesized that developmental sub-chronic low-level lead exposure would increase microglial cell numbers within the DG and that apigenin treatment may mitigate these effects. A significant effect of treatment group was found and post-hoc analyses revealed that Pb-exposure generated an increased number of microglial cells as compared to controls. Interestingly, the 30 ppm Pb with apigenin treatment group did not generate microglial cell numbers different from the control group unexposed to Pb. These results suggested that developmental sub-chronic low-level lead exposure increased microglial cell activation within the DG and that, at low-levels of Pb exposure, apigenin treatment may mitigate these effects. These results provided the groundwork for studies that could identify an effective intervention to alleviate the effects of developmental chronic low-level lead exposure in child neurocognition.

Oxidative Stress is a New Avenue for Treatment of Neuropsychiatric Disorders: Hype of Hope?

The biochemical integrity of the brain is critical in maintaining normal central nervous system (CNS) functions. One of the factors that plays an important role in causing biochemical impairment of the brain is known as oxidative stress. Oxidative stress is generally defined as the excessive formation of free radicals relative to antioxidant defenses. The brain is particularly susceptible to oxidative stress because of its high oxygen consumption and lipid-rich content. Therefore, oxidative stress damage is associated with abnormal CNS function. Psychiatric disorders are debilitating diseases. The underlying pathophysiology of psychiatric disorders is poorly defined and may involve the interplay of numerous clinical factors and mechanistic mechanisms. Considerable evidence suggests that oxidative stress plays a complex role in several neuropsychiatric disorders, including anxiety, bipolar disorder, depression, obsessivecompulsive disorder, panic disorder, and schizophrenia. To address these issues, we reviewed the literature and considered the role of oxidative stress as one of the first pathological changes in the course of neuropsychiatric disorders, which should receive more attention in future research.

Predictive value analysis of albumin-related inflammatory markers for short-term outcomes in patients with In-hospital cardiac arrest

ABSTRACT Objective This study investigated the predictive value of albumin-related inflammatory markers for short-term outcomes in in-hospital cardiac arrest (IHCA) patients. Methods A linear mixed model investigated the dynamic changes of markers within 72 hours after return of spontaneous circulation (ROSC). Time-Dependent COX regression explored the predictive value. Mediation analysis quantified the association of markers with organ dysfunctions and adverse outcomes. Results Prognostic Nutritional Index (PNI) and RDW-Albumin Ratio (RAR) slightly changed (p > 0.05). Procalcitonin-Albumin Ratio (PAR1) initially increased and then slowly decreased. Neutrophil-Albumin Ratio (NAR) and Platelet-Albumin Ratio (PAR2) decreased slightly during 24-48 hours (all p＜0.05). PNI (HR = 1.646, 95%CI (1.033,2.623)), PAR1(HR = 1.69, 95%CI (1.057,2.701)), RAR (HR = 1.752,95%CI (1.103,2.783)) and NAR (HR = 1.724,95%CI (1.078,2.759)) were independently associated with in-hospital mortality. PNI (PM = 45.64%, 95%CI (17.05%,87.02%)), RAR (PM = 45.07%,95%CI (14.59%,93.70%)) and NAR (PM = 46.23%,95%CI (14.59%,93.70%)) indirectly influenced in-hospital mortality by increasing SOFA (central) scores. PNI (PM = 21.75%, 95%CI(0.67%,67.75%)) may also indirectly influenced outcome by increasing SOFA (renal) scores (all p＜0.05). Conclusions Within 72 hours after ROSC, albumin-related inflammatory markers (PNI, PAR1, RAR, and NAR) were identified as potential predictors of short-term prognosis in IHCA patients. They may mediate the adverse outcomes of patients by causing damages to the central nervous system and renal function.