Neurotransmitter Imbalance Research Articles

Neurotransmitter Dysregulation in Sleep and Circadian Rhythms: Implications for Postpartum Depression

Postpartum depression (PPD) is a major mental health disorder that affects mothers both emotionally and physically, hindering their ability to care for the child. Other neurotransmitter imbalances during the postpartum period include serotonin, dopamine, melatonin, GABA, and orexin, which result in disturbances in sleep. The reduction in serotonin concentration is related to mood and sleep, while altered dopamine levels are related to alertness and coordinating circadian rhythms. Further, women postpartum demonstrates higher melatonin levels and a subsequent neuronal excitation due to lesser functioning GABA-A receptors, which in addition combine to cause disturbances with sleep. This paper reviews the literature to analyze the effects of neurotransmitter disorders in sleep and circadian rhythm on postpartum depression. The review provides emerging treatment options for postpartum depression including selective serotonin reuptake inhibitors (SSRIs), melatonin agonists, and benzodiazepines, which have shown promising results in relieving symptoms by modulating neurotransmitter pathways. However, more research needs to be undertaken in the field of non-pharmacological interventions, the long-term outcome of neurotransmitter dysregulation, and preventive measures during pregnancy that would go a long way toward improving overall outcomes for mothers as well as their infants.

Psychosomatic influences on insomnia: Mechanisms, diagnosis, and treatment strategies

Insomnia is the most prevalent sleep disorder with significant implications for mental and physical health. While traditionally understood through a biomedical lens, increasing evidence highlights the role of psychosomatic factors in its onset and perpetuation. This narrative review explores the relationship between psychological and somatic influences on insomnia, examining the underlying mechanisms, diagnostic challenges, and treatment strategies. We discuss neurobiological pathways, including the hypothalamic–pituitary–adrenal axis and neurotransmitter imbalances, alongside psychological factors such as anxiety, hyperarousal, and cognitive distortions. Somatic symptoms, particularly chronic pain, and other physical conditions are also regarded as integral contributors to insomnia. Diagnosis of psychosomatic insomnia requires a comprehensive approach that incorporates both psychological and physical assessments, utilizing a combination of clinical interviews, standardized questionnaires, and differential diagnostic techniques. Treatment strategies are discussed in this paper with an emphasis on cognitive-behavioral therapy for insomnia, pharmacological interventions, and integrative approaches that address the multifaceted nature of the disorder. The review also highlights the importance of lifestyle modifications and the potential role of alternative therapies in managing insomnia. A rounded understanding of psychosomatic influences is crucial for effective diagnosis and treatment of insomnia. Future research should focus on personalized therapeutic approaches and further interpreting the complex interconnections between mind and body in the pathophysiology of insomnia. This perspective has the potential to enhance clinical practice and improve outcomes for individuals suffering from this challenging disorder.

Agmatine Attenuates Behavioral and Biochemical Alterations in Rats Exposed to Ethanol during Adolescence

Background: Ethanol is a psychoactive substance and its use throughout adolescence may have a role in the development of alcoholism in adulthood which causes behavioral changes and structural alterations in particular brain regions that may be the source of these cognitive and motor impairments. As an endogenous amine, agmatine has drawn a lot of interest in relation to drug addiction and its aftereffects. It is an endogenous neuromodulator that has been shown to be a potential agent to manage diverse central nervous system (CNS) disorders. The current investigation aims to elucidate the role of agmatine in mediating behavioral alterations resulting from prolonged exposure to ethanol in rats during their early adolescent years. Methods: Rats received saline (1 ml/kg, p.o.) or ethanol (5 g/kg/day, 35% v/v) once a day from PND 28 to PND 49. Chronic ethanol intoxication during the CNS developing may induce sustainable neurobehavioral alterations in rats. After PND 70, the rats were subjected to behavioural and biochemical tests. Results: Chronic ethanol exposure significantly reduced locomotor activity, increased anxiety-like and depressive behaviors, and impaired cognitive function in adolescent rats. These behavioral alterations were accompanied by elevated oxidative stress, decreased hippocampal BDNF levels, increased levels of proinflammatory cytokines, and disrupted neurotransmitter balance. Agmatine administration at both 40 mg/kg and 80 mg/kg doses notably improved locomotor activity, reduced anxiety and depressive behaviors, and enhanced cognitive performance. Additionally, agmatine treatment reduced oxidative stress, restored BDNF levels, normalized TNF-α and IL6 levels, and corrected the neurotransmitter imbalance in ethanol-exposed rats. Conclusion: Prolonged exposure to ethanol during adolescence elicits persistent behavioural changes, characterized by diminished spontaneous locomotion and impaired balance. Administration of Agmatine effectively restores locomotor activity, alleviates anxiety and depression, and enhances both spatial learning and recognition memory in rats exposed to ethanol. Additionally, agmatine treatment attenuates oxidative stress indicators, including nitrite and lipid peroxidation levels, specifically in the cerebral cortex. These findings suggest that Agmatine holds potential as a viable therapeutic intervention for mitigating both the behavioural and biochemical repercussions induced by ethanol exposure in the rat model.

Upregulation of cAMP/PKA/CREB signaling mediated by GABABR might contribute to the amelioration effects of sea cucumber peptides (Acaudina leucoprocta) on cognitive dysfunction in mice

This study aimed to determine the effects and underlying mechanisms of sea cucumber peptides (SCP) obtained from Acaudina leucoprocta in mitigating induced by D-galactose cognitive dysfunction in mice. Additionally, it aimed to validate the cognitive-enhancing potential of peptides identified via in silico and peptidomics using SH-SY5Y cells. The results demonstrated significant improvement in behavioral performance with oral administration of SCP. Additionally, SCP normalized oxidative stress and neurotransmitter imbalances (especially gamma-aminobutyric acid, GABA). Also, SCP effectively rectified gut microbiota dysbiosis. Mechanistically, SCP activated the γ-aminobutyric acid type B receptors (GABABR)/ cyclic adenosine monophosphate (cAMP)/ cAMP-dependent protein kinase A (PKA)/ cAMP response element-binding protein (CREB) axis to promote GABA release and alleviate neuronal and oxidative stress damage, which subsequently ameliorated cognitive dysfunction. Furthermore, docking analysis predicted the binding of fourteen peptides with high abundance and PeptideRanker scores to GABABR. Notably, Lys-Gly-Phe-Pro (KGFP) had the strongest binding affinities and actively interacted with GABABR sites through hydrogen bonds, van der Waals, hydrophobic, and electrostatic interactions. The capacity of KGFP to improve cognitive function was further demonstrated when the SH-SY5Y cells were subjected to D-galactose. These results imply that the implementation of SCP intervention could be a useful tactic for improving cognitive function.

기능성 소화불량증의 기능의학적 접근: 뇌-장축 불균형 1예와 위산저하증 2예

Functional dyspepsia is a common gastrointestinal disorder typically treated with proton pump inhibitors or gastrointestinal motility agents. However, these treatments can sometimes be ineffective or even worsen symptoms. Therefore, it may be more beneficial to identify and address the root causes of the symptoms rather than relying solely on standard treatments. Addressing the root issues of functional dyspepsia can be more effective than merely using gastrointestinal medications. First, gastrointestinal symptoms may arise from hormonal imbalances, autonomic nervous system dysfunctions, and neurotransmitter imbalances, all of which indicate imbalances of brain-gut axis. Correcting these imbalances can significantly alleviate symptoms. Second, a comprehensive approach to functional medicine in gastrointestinal health should include not only hyperacidity and hypersensitivity but also conditions like hypochlorhydria, along with associated nutritional deficiencies and small intestinal bacterial overgrowth. Integrating clinical nutritional treatments alongside these considerations can further enhance symptom relief. This paper reviewed the related literature and reported three related cases.

Neuroprotective Potential of Tanshinone-IIA in Mitigating Propionic Acidinduced Experimental Autism-like Behavioral and Neurochemical Alterations: Insights into c-JNK and p38MAPK Pathways.

Autism is a neurodevelopmental disorder associated with mitochondrial dysfunction, apoptosis, and neuroinflammation. These factors can lead to the overactivation of c-JNK and p38MAPK. In rats, stereotactic intracerebroventricular (ICV) injection of propionic acid (PPA) results in autistic-like characteristics such as poor social interaction, repetitive behaviours, and restricted communication. Research has demonstrated the beneficial effects of phytochemicals derived from plants in treating neurological disorders. Tanshinone-IIA (Tan-IIA) is a chemical found in the root of Salvia miltiorrhiza. It has neuroprotective potential by inhibiting c-JNK and p38MAPK against behavioral and neurochemical alterations in PPA-induced autistic rats. We observe behavioral changes, alterations in apoptotic markers, myelin basic protein (MBP), neurofilament-Light (NEFL), inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and neurotransmitter imbalances using different brain regions (cerebral cortex, hippocampus, striatum), as well as biological samples, cerebrospinal fluid (CSF), and blood plasma. Persistent administration of 30 mg/kg and 60 mg/kg Tan-IIA via intraperitoneal injection reduced these alterations dose-dependently. Anisomycin (3 mg/kg.,i.p.) as a SAPK (c-JNK and p38MAPK) agonist was administered to assess the neuroprotective effect of Tan-IIA in autistic rats. Tan- IIA's molecular interactions with c-JNK and p38MAPK were confirmed using silico analysis. We also observed gross morphological, histopathological, and Luxol Fast Blue (LFB) myelin straining changes in whole and coronal brain sections. Thus, Tan-IIA has a neuroprotective potential by inhibiting the c-JNK and p38MAPK signalling pathways, which reduces the behavioral and neurochemical abnormalities induced by PPA in adult Wistar rats, indicating that current results should be studied further for the diagnosis and treatment of autism.

Repeated exposure to ethanol alters memory acquisition and neurotransmission parameters in zebrafish brain

Alcohol is widely consumed worldwide and its abuse can cause cognitive dysfunction, affecting memory and learning due to several neurophysiological changes. An imbalance in several neurotransmitters, including the cholinergic and glutamatergic systems, have been implicated in these effects. Zebrafish are sensitive to alcohol, respond to reward stimuli, and tolerate and exhibit withdrawal behaviors. Therefore, we investigated the effects of repetitive exposure to ethanol (REE) and the NMDA receptor antagonist dizocilpine (MK-801) on memory acquisition and glutamatergic and cholinergic neurotransmission. Memory was assessed using the inhibitory avoidance and object recognition tasks. Brain glutamate levels and the activity of Na+-dependent transporters were evaluated as indexes of glutamatergic activity, while acetylcholinesterase (AChE) and choline acetyltransferase (ChAT), enzyme activity were evaluated as indexes of cholinergic activity. Behavioral assessments showed that REE impaired aversive and spatial memory, an effect that MK-801 mimicked. Glutamate levels, but not transporter activity, were significantly lower in the REE group; similarly, REE increased the activity of AChE, but not ChAT, activity. These findings suggest that intermittent exposure to ethanol leads to impairments in zebrafish memory consolidation, and that these effects could be associated with alterations in parameters related to neurotransmission systems mediated by glutamate and acetylcholine. These results provide a better understanding of the neurophysiological and behavioral changes caused by repetitive alcohol use.

A potential treatment of schizophrenia through mitigating the neurotransmitter imbalance: ADX71149

A potential treatment of schizophrenia through mitigating the neurotransmitter imbalance: ADX71149

Unprecedented Co-occurrence: Identification of a Pathogenic Genetic Variant in the KMT2B Gene in a Wilson Disease Patient with a Pathogenic ATP7B Mutation

The pathophysiology of dystonia in Wilson disease (WD) is complex and poorly understood. Copper accumulation in the basal ganglia, disrupts dopaminergic pathways, contributing to dystonia’s development via neurotransmitter imbalance. Despite advances in diagnosis and management, WD with dystonia remains a challenging condition to treat. We aim to report the unprecedented co-occurrence of pathogenic genetic variants in both the ATP7B and KMT2B genes in a patient with WD. A 13-year-old male presented at 12 with dysarthria and bilateral Kayser-Fleischer rings. Over months, dystonia spread to his left foot, upper limb, and trunk, accompanied by slowed daily activities. Diagnostic tests included MRI for brain structure, abdominal ultrasound for liver function, serum ceruloplasmin and copper levels to assess copper metabolism, and 24-hour urine copper tests for excretion levels. Whole exome sequencing was conducted using genomic DNA from peripheral blood samples. Variant classification followed guidelines from the American College of Medical Genetics and Genomics. The sequencing revealed compound heterozygous pathogenic variants in the ATP7B gene: NM_000053.4:c.2165dupT and NM_000053.4:c.813C>A. A pathogenic variant in the KMT2B gene, NM_014727:c.3052delA, was identified. This case highlights WD co-occurrence with ATP7B and KMT2B mutations, suggesting KMT2B as a potential genetic modifier.

Organophosphate Insecticide Malathion Induces Alzheimer's Disease-Like Cognitive Impairment in Mice: Evidence of the Microbiota-Gut-Brain Axis.

Evidence suggests that exposure to organophosphate pesticides increases the risk of neurodegenerative diseases, but the mechanisms remain unclear. This study investigated the effects of malathion on Alzheimer's disease (AD)-like symptoms at environmentally relevant concentrations using wild-type (WT) and APP/PS1 transgenic mouse models. Results showed that malathion exposure induced AD-like cognitive impairment, amyloid-β (Aβ) accumulation, and neuroinflammation in WT mice, with worsened symptoms in APP/PS1 mice. Mechanistic studies revealed that malathion induced AD-like gut microbiota dysbiosis (reduced Lactobacillus and Akkermansia, and increased Dubosiella), causing gut barrier impairment and tryptophan metabolism disruptions. This resulted in a significant increase in indole derivatives and activation of the colonic aryl hydrocarbon receptor (AhR), promoting the kynurenine (KYN) pathway while inhibiting the serotonin (5-HT) pathway. Increased neurotoxic KYN metabolites (3-hydroxykynurenine and quinolinic acid) triggered gut and systemic inflammation, upregulating hippocampal IL-6 and IL-1β mRNA levels and thereby causing neuroinflammation. Gut tryptophan metabolism disruptions caused hippocampal neurotransmitter imbalances, reducing the levels of 5-HT and its derivatives. These effects promoted AD progression in both WT and APP/PS1 mice. This study highlights the crucial role of the microbiota-gut-brain axis in AD-like cognitive impairment induced by malathion exposure, providing insights into the neurodegenerative disease risks posed by organophosphate pesticides.

Features оf Changes in the Level of Neurotransmitters and Markers of Neurodegeneration in the Brain of Rats with Experimental Parkinson’s Disease Against the Background of Course Therapy with Steroid Glycoalkaloids

Parkinson’s disease is a chronic neurodegenerative disease, one of the pathobiochemical manifestations of which is an imbalance of neurotransmitters in the brain. The aim of this work is to study the effect of glycoalkaloids on changes in the level of neurotransmitters and markers of brain neurodegeneration in rats with experimental Parkinson’s disease. Parkinson’s disease was modeled in animals by intracerebral administration of rotenone. The studied glycoalkaloids were administered orally at a dose of 0.06 mg / kg, a course of 28 days after pathology modeling. The study found that the use of the analyzed glycoalkaloids did not affect the concentration of dopamine and serotonin, and also significantly (p 0.05) reduced the level of ACh by 35.9% and increased the level of GABA by 55.1%, reduced the concentration of S100β protein by 68.6% and increased the level of BDNF by 52.4%.

Multifunctional, Fluorene-Based Modulator of Cholinergic and GABAergic Neurotransmission as a Novel Drug Candidate for Palliative Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and behavioral and psychological symptoms of dementia (BPSD). Given that cholinergic neurons are predominantly affected in AD, current treatments primarily aim to enhance cholinergic neurotransmission. However, imbalances in other neurotransmitters, such as γ-aminobutyric acid (GABA), also contribute to AD symptomatology. In the presented research, using a combination of crystallography and computational methods we developed compound 6 as a dual modulator of GABAergic and cholinergic neurotransmission systems. Compound 6 demonstrated inhibition of BuChE (IC50=0.21 μM) and GABA transporter 1 (IC50=10.96 μM) and 3 (IC50=7.76 μM), along with a favorable drug-likeness profile. Subsequent in vivo studies revealed the effectiveness of 6 in enhancing memory retention and alleviating anxiety and depression symptoms in animal models, while also proving safe and bioavailable for oral administration. The innovative multi-target-directed ligand 6 offers a new approach to treating cognitive deficits and BPSD in AD.

Microbiome-based therapies for Parkinson's disease.

The human gut microbiome dysbiosis plays an important role in the pathogenesis of Parkinson's disease (PD). The bidirectional relationship between the enteric nervous system (ENS) and central nervous system (CNS) under the mediation of the gut-brain axis control the gastrointestinal functioning. This review article discusses key mechanisms by which modifications in the composition and function of the gut microbiota (GM) influence PD progression and motor control loss. Increased intestinal permeability, chronic inflammation, oxidative stress, α-synuclein aggregation, and neurotransmitter imbalances are some key factors that govern gastrointestinal pathology and PD progression. The bacterial taxa of the gut associated with PD development are discussed with emphasis on the enteric nervous system (ENS), as well as the impact of gut bacteria on dopamine production and levodopa metabolism. The pathophysiology and course of the disease are associated with several inflammatory markers, including TNF-α, IL-1β, and IL-6. Emerging therapeutic strategies targeting the gut microbiome include probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). The article explored how dietary changes may affect the gut microbiota (GM) and the ways that can affect Parkinson's disease (PD), with a focus on nutrition-based, Mediterranean, and ketogenic diets. This comprehensive review synthesizes current evidence on the role of the gut microbiome in PD pathogenesis and explores its potential as a therapeutic target. Understanding these complex interactions may assist in the development of novel diagnostic tools and treatment options for this neurodegenerative disorder.

Premenstrual Syndrome: An Overview of the Review Analysis, and Potential Role of Herbal and Dietary Supplements

: A premenstrual syndrome is a group of regular physiological, mental, emotional, and behavioral symptoms that appear periodically in the luteal phase of the menstrual cycle, and they vanish quickly with the beginning of menstruation or a few days afterward. Thus, severe premenstrual syndrome (PMS) affects 5–8% of women; the majority of these individuals also match the factors for premenstrual dysphoric disorder (PMDD). Premenstrual syndrome typically includes physical problems like headache, tiredness, indigestion, insomnia, nausea, and breast tenderness as well as symptoms associated with emotions (mood swings, anxiousness, and aggressiveness). Although the true mechanism of PMS is unknown, a number of theories point to increased sensitivity to typical hormonal changes and imbalances in neurotransmitters. A multidisciplinary team using an integrative holistic approach in the direction of an individualized strategy gradually manages PMS. The first phase entails educating women about PMS, self-screening, herbs like St John’s Wort, chaste berry, saffron; ginkgo biloba; chamomile, evening primrose, turmeric and so on, various nutrition supplements as Vitamin B6; calcium; magnesium and lifestyle adjustments like dietary modifications; exercise; yoga; sleep hygiene. The second step involves implementing various relaxation therapies, cognitive behavioral therapy (CBT), stress reduction techniques, and acupuncture. The available treatment as various drugs like SSRIs; serotonergic antidepressants; anxiolytics and hormonal therapy that are used currently to treat PMS, exhibits unwanted side effects. Therefore, this issue and other similar gynecological conditions have been discussed and managed with herbal medicines and other natural solutions in this comprehensive piece of work.

Neuro-pharmacological Assessment of Coleus forskohlii for Anti-compulsive Activity in Swiss Albino Mice

Background: Obsessive-Compulsive Disorder (OCD) is a common psychiatric illness characterized by obsessions or compulsions that significantly disrupt or impair daily functioning. Coleus forskohlii, a significant medicinal crop, has forskolin in its roots. It is utilized extensively as food and medicine all over the world. Coleus forskohlii has reputed medicinal uses, which include antidepressant, antiaggregant, cAMP-genic, anticancer, etc. Objective: This study used mice models of marble burying and nestlet shredding to assess the potential efficacy of Coleus forskohlii against obsessive-compulsive disorder. 8-hydroxy-2-(di-npropylamino) tetralin (8-OH-DPAT) induced compulsive checking can demonstrate OCD-like repetitive and obsessive behavior as well as neurotransmitter imbalance (serotonin). Methods: Each group had six mice, and the therapy was administered to the animals for a total of 15 days. On days 1, 7, and 14, the marble burying test was assessed for 30 minutes, and on days 2, 8 and 15, the nestlet shredding test was assessed for 30 minutes. The T-maze paradigm was used to assess anti-OCD activity. The brain histology and morphometry were also performed. Results: When compared to the control group, treatments with Coleus forskohlii (50 and 100 mg/kg, p.o.) significantly enhanced performance on both behavior tests. The SAB score is dramatically increased following the administration of the 8-OH-DPAT (2 mg/kg, i.p.) group. Coleus forskohlii (50 and 100 mg/kg, p.o.) and fluoxetine (15 mg/kg, p.o.) groups showed significantly lowered results. Animals treated with 8-OH-DPAT showed a considerable reduction in serotonin levels. Following Coleus forskohlii administration, the histology of the brain tissues showed normal morphological structure with no toxicity or abnormalities. Conclusion: The combination of all these findings points to Coleus forskohlii delivering a possible therapeutic option for the treatment of OCD. The identification and anticompulsive properties of the components from Coleus forskohlii should be the main aim of future studies.

Elevated Posterior Insula Glutamate in Patients with Sickle Cell Disease

Sickle cell disease (SCD) is an inherited hemolytic disorder accompanied by chronic pain and recurrent acute painful episodes known as vaso-occlusive crises (VOCs). Increased Glx (glutamate+glutamine) and lowered insula GABA concentration has been reported in the insula of patients with fibromyalgia, a nociplastic chronic pain condition, and may affect the pathophysiology of pain-related syndromes. Therefore, proton magnetic resonance spectroscopy (1H-MRS) was conducted to measure levels of Glx and other brain metabolites using a single voxel (size: 2×3×3 cm3) in the right posterior insula cortex (PIC) in 17 individuals with SCD and 17 ethnicity-, age- and sex-matched healthy controls (HCs). The frequency of VOCs in the preceding 12 months was recorded. The concentration of Glx (p=0.019) and the ratio of Glx to tCr (total creatine, p=0.035) in the PIC were significantly higher in patients with SCD as compared to matched HCs (n=17). Secondary analyses with the unpaired full sample of 24 SCD also showed a significantly higher level of Glx/tCr than HCs (n=19), with a positive correlation between the level of Glx/tCr and the number of VOCs (p=0.034, r=0.476), as well as a negative correlation between Glx and sensory sensitivity assessed by tonic pressure pain in gastrocnemius area of the non-dominant leg (p=0.040, r=-0.462). The unpaired full sample additionally revealed a significant difference in sensory sensitivity (p=0.050). Altered metabolites such as GABA and myoinositol were also observed between SCD and HCs. These results suggest that elevated excitatory neurotransmission in the insula might contribute to nociplastic pain in SCD. PerspectiveOur work highlighted the innovative finding of elevated levels of the excitatory neurotransmitter glutamate with glutamine in patients with SCD compared to healthy controls. The trend of positive relationship between Glx/tCr and the frequency of VOCs suggests that an excitatory brain neurotransmitter imbalance may be involved in VOCs.

ИННОВАЦИОННЫЕ МЕТОДЫ ДИАГНОСТИКИ БРУКСИЗМА В СОВРЕМЕННОЙ СТОМАТОЛОГИИ

The article is devoted to one of the most important problems in modern dentistry – bruxism. The relevance is associated with an increase in the prevalence of bruxism in patients of different age groups. The article discusses etiological factors, clinical manifestations and various diagnostic methods for patients with bruxism. The material of the review is the long-term research of domestic and foreign scientists devoted to the etiology and modern diagnosis of patients with bruxism. Using the Elibrary search engine, 17 articles were selected for the time period from 2003 to 2023. The article uses a descriptive method that allowed us to consider the current state of the problem and outline ways to further solve it. The main content of the study is the analysis of innovative methods for the diagnosis of bruxism, which make it possible to diagnose pathology at the initial stage of the disease and start its treatment in a timely manner. The article emphasizes the need to supplement existing clinical recommendations with innovative methods and diagnostic tools for this pathology. As a result of the analysis of the literature, the authors developed a systematization of all methods of diagnosing bruxism by the subject of the study. The article discusses research aimed at studying the occlusal relationship of the jaws, the diagnosis of a psychopathological condition, the diagnosis of musculoskeletal dysfunction, the diagnosis of neurotransmitter imbalance and the detection of diseases of the musculoskeletal system. The authors concluded that with the advent and introduction of computer technologies into dental practice, innovative methods and tools for diagnosing bruxism were developed, which led to a significant improvement in the quality of dental care provided. Special attention is paid in the article to the importance of the principle of primacy and an interdisciplinary approach in conducting diagnostic studies aimed at identifying bruxism.

Nano-formulations for the Management of Epilepsy: Synthetic and Herbal Drug Perspectives

Introduction: Epilepsy is a multifaceted neurological disorder impacting many individuals globally. Although the main treatment method is through medicines, many patients do not respond to existing drugs. This has spurred extensive research for new therapeutic targets and drug delivery methods. Inflammation and oxidative stress have been associated with the development and progression of epilepsy. Nanomedicine-based treatments focussing on these pathways could provide a promising way to enhance treatment results. Objective: This review aims to provide insights into enhancing antiepileptic therapy through the development of nanoformulations of synthetic and herbal drugs. Methods: A comprehensive review of existing literature was conducted to evaluate the potential of nanoformulations in improving the delivery and efficacy of antiepileptic drugs. The review covers the pathophysiological hypotheses of epilepsy, including the glutamatergic, GABAergic, oxidative stress, and neuroinflammation hypotheses, and examines the role of neurotransmitter imbalances in seizure activity. Results: Nanoformulations offer promising advantages for epilepsy treatment by enhancing drug delivery across the blood-brain barrier, reducing required dosages, and minimizing side effects. The utilization of nanoparticles can improve the bioavailability and targeting of AEDs, potentially leading to better seizure control. However, challenges such as ensuring biocompatibility and optimizing nanoparticle characteristics remain. Conclusion: While significant progress has been made in understanding epilepsy and developing treatments, the disorder continues to pose challenges. Nanoformulations represent a promising area of research that could lead to more effective and targeted therapies for epilepsy, although further studies are needed to address the associated challenges and fully realize their potential.

Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine.

Viral infections are increasingly recognized as triggers for depressive disorders, particularly following the SARS-CoV-2 pandemic and the rise of long COVID. Viruses such as Herpes Simplex Virus (HSV), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), and Human Immunodeficiency Virus (HIV) are linked to depression through complex neurobiological mechanisms. These include immune system dysregulation, chronic inflammation, and neurotransmitter imbalances that affect brain function and mood regulation. Viral activation of the immune system leads to the release of pro-inflammatory cytokines, resulting in neuroinflammation and associated depressive symptoms. Furthermore, specific viruses can disrupt neurotransmitter systems, including serotonin, dopamine, and glutamate, all of which are essential for mood stabilization. The unique interactions of different viruses with these systems underscore the need for virus-specific therapeutic approaches. Current broad-spectrum treatments often overlook the precise neurobiological pathways involved in post-viral depression, reducing their efficacy. This review emphasizes the need to understand these virus-specific interactions to create tailored interventions that directly address the neurobiological effects induced by each type of virus. These interventions may include immunomodulatory treatments that target persistent inflammation, antiviral therapies to reduce the viral load, or neuroprotective strategies that restore neurotransmitter balance. Precision medicine offers promising avenues for the effective management of virus-induced depression, providing patient-specific approaches that address the specific biological mechanisms involved. By focusing on the development of these targeted treatments, this review aims to pave the way for a new era in psychiatric care that fully addresses the root causes of depression induced by viral infections.

Long-Term Neurotoxic Effects and Alzheimer's Disease Risk of Early EHDPP Exposure in Zebrafish: Insights from Molecular Mechanisms to Adult Pathology.

2-Ethylhexyl diphenyl phosphate (EHDPP), ubiquitously monitored in environmental media, is highly bioaccumulative and may pose long-term risks, even after short-term exposure. In this investigation, larval zebrafish were exposed to 0.05, 0.5, and 5.0 μg/L EHDPP from 4 to 120 h postfertilization (hpf) to examine the long-term neurotoxicity effects of early exposure. Exposure to 5.0 μg/L EHDPP yielded hyperactive locomotor behavior, which was characterized by increased swimming speed, larger turning angles, and heightened sensitivity to light-dark stimulation. The predicted targets of EHDPP (top 100 potential macromolecules) were primarily associated with brain diseases like Alzheimer's disease (AD). Comparisons of differentially expressed genes (DEGs) from AD patients (GSE48350) and RNA-seq data from EHDPP-exposed zebrafish confirmed consistently abnormal regulatory pathways. EHDPP's interaction with M1 and M5 muscarinic acetylcholine receptors likely disrupted calcium homeostasis, leading to mitochondrial dysfunction and neurotransmitter imbalance as well as abnormal locomotor behavior. Especially, 5.0 μg/L EHDPP exposure during early development (4-120 hpf) triggered early- and midstage AD-like symptoms in adulthood (180 dpf), characterized by cognitive confusion, aggression, blood-brain barrier disruption, and mitochondrial damage in brains. These findings provide deep insights into the long-term neurotoxicity effects and Alzheimer's disease risks of early EHDPP exposure at extremely low dosages.