Sensors and Actuators B Chemical, Год журнала: 2023, Номер 404, С. 135246 - 135246
Опубликована: Дек. 29, 2023
Язык: Английский
Nutrients, Год журнала: 2023, Номер 15(20), С. 4391 - 4391
Опубликована: Окт. 16, 2023
Schizophrenia, a severe mental illness affecting about 1% of the population, manifests during young adulthood, leading to abnormal function and behavior. Its multifactorial etiology involves genetic factors, experiences adversity, infection, gene-environment interactions. Emerging research indicates that maternal infection or stress pregnancy may also increase schizophrenia risk in offspring. Recent on gut-brain axis highlights gut microbiome's potential influence central nervous system (CNS) health, including schizophrenia. The microbiota, located digestive system, has significant role play human physiology, immune development, vitamin synthesis, protection against pathogenic bacteria. Disruptions caused by diet, medication use, environmental pollutants, stress, lead imbalances with far-reaching effects CNS health. Of interest are short-chain fatty acids (SCFAs), metabolic byproducts produced microbes fermentation. SCFAs can cross blood-brain barrier, influencing activity, microglia cytokine modulation. dysregulation neurotransmitters contribute disorders, This review explores relationship between SCFAs, microbiome, Our aim is deepen understanding elucidate its implications for future therapeutic approaches.
Язык: Английский
Процитировано
35
Neuropsychiatric Disease and Treatment, Год журнала: 2024, Номер Volume 20, С. 607 - 620
Опубликована: Март 1, 2024
Schizophrenia is a disease with complex pathological mechanism that influenced by multiple genes. The study of its pathogenesis dominated the dopamine hypothesis, as well other hypotheses such 5-hydroxytryptamine glutamate immune-inflammatory gene expression abnormality and neurodevelopmental hypothesis. first generation antipsychotics was developed based on dopaminergic receptor antagonism, which blocks D2 receptors in brain to exert antipsychotic effects. second acts dual blockade receptors. From third onwards, therapeutic targets for schizophrenia expanded beyond explore partial agonism effects new D3, 5-HT1A, 5-HT7, mGlu2/3 main advantages over first-generation are reduction side improvement negative symptoms, even though third-generation do not directly block receptors, modulation transmitter system still an important part their process. According recent research, several including 5-hydroxytryptamine, glutamate, γ-aminobutyric acid, acetylcholine norepinephrine, play role development schizophrenia. Therefore, focus developing drugs has shifted towards or inhibition these Specifically, NMDARs stimulants, GABA agonists, mGlu modulators, cholinergic 5-HT2C agonists alpha-2 modulators become direction. Animal experiments have confirmed drugs, but pharmacokinetics clinical applicability require further exploration. Research alternative receptor, potential treatment options gives way address challenge refractory This article aims provide comprehensive overview research medications schizophrenia, offering valuable insights both this field.
Язык: Английский
Процитировано
11
The Lancet Psychiatry, Год журнала: 2025, Номер unknown
Опубликована: Апрель 1, 2025
New treatment options are needed for adolescent schizophrenia, partly due to an unfavourable risk-benefit profile of current options. This trial aimed evaluate the short-term efficacy and safety brexpiprazole in adolescents with schizophrenia. multicountry, randomised, double-blind, parallel-arm, placebo-controlled, phase 3 active reference was done at 62 outpatient sites ten countries. Eligible patients were aged 13-17 years a primary DSM-5 diagnosis schizophrenia Positive Negative Syndrome Scale (PANSS) total score ≥80 screening baseline. Patients randomly assigned (1:1:1) oral 2-4 mg/day, placebo, or aripiprazole 10-20 mg/day (active reference). Patients, investigators, sponsor personnel masked assignment. The endpoint change from baseline week 6 PANSS (in who took least one dose study drug had post-baseline evaluations). Safety assessed drug. People lived experience not involved research writing process. registered ClinicalTrials.gov, NCT03198078, is complete. Between June 29, 2017, Feb 23, 2023, 376 screened, 316 (n=110), placebo (n=104), (n=102). mean age 15·3 (SD 1·5). 166 (53%) female 150 (47%) male. Of patients, seven (2%) American Indian Alaskan Native, two (1%) Asian, 21 (7%) Black African American, 204 (65%) White, 81 (26%) other, as reported using US Census Bureau classifications. Mean doses last visit 3·0 mg 0·9) 13·9 (4·7), respectively. Least squares -22·8 (SE 1·5) -17·4 (1·6) (least difference -5·33 [95% CI -9·55 -1·10]; p=0·014). corresponding -24·0 1·6; versus -6·53 -10·8 -2·21]; pnominal=0·0032, adjusted multiple testing). Treatment-emergent adverse events 44 (40%) 110 group, 42 104 53 (52%) 102 group. most common (incidence ≥5%) treatment-emergent headache (n=7) nausea somnolence (n=11), fatigue (n=8), akathisia aripiprazole. Serious by three (3%) No deaths reported. In associated greater reduction symptom severity than over weeks. consistent trials adult patients. These results add body evidence might help inform selection clinical practice. Otsuka Pharmaceutical Development & Commercialization H Lundbeck.
Язык: Английский
Процитировано
1
PLoS Computational Biology, Год журнала: 2022, Номер 18(9), С. e1010506 - e1010506
Опубликована: Сен. 13, 2022
Dendrites of cortical pyramidal cells are densely populated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, a.k.a. I h channels. channels targeted multiple neuromodulatory pathways, and thus one the key ion-channel populations regulating cell activity. Previous observations theories attribute opposing effects on neuronal excitability due to their mildly hyperpolarized reversal potential. These difficult measure experimentally fine spatiotemporal landscape activity in dendrites, but computational models provide an efficient tool for studying this question a reduced generalizable setting. In work, we build upon existing biophysically detailed thick-tufted layer V model over- under-expression as well neuromodulation. We show that facilitate action potentials response proximal dendritic stimulus while they hinder distal at apical dendrite. also inhibitory is interactions between hot zone low voltage-activated Ca 2+ Our simulations suggest combination -enhancing neuromodulation part dendrite -inhibiting modulation can increase more than either two alone. analyses uncover -channel single-cell level shed light how these neurons integrate information enable higher-order functions brain.
Язык: Английский
Процитировано
33
Molecular Psychiatry, Год журнала: 2023, Номер 28(6), С. 2277 - 2290
Опубликована: Май 11, 2023
Язык: Английский
Процитировано
21
Frontiers in Molecular Neuroscience, Год журнала: 2023, Номер 16
Опубликована: Апрель 24, 2023
Many neurodegenerative diseases including Alzheimer’s disease, Parkinson’s and amyotrophic lateral sclerosis are characterized by the accumulation of pathogenic proteins abnormal localization organelles. These pathological features may be related to axonal transport deficits in neurons, which lead failures protein targeting specific sites for degradation organelle transportation designated areas needed normal physiological functioning. Axonal most likely early events such gradually loss integrity other degenerative changes. In this review, we investigated reports mechanisms underlying development a variety common diseases, as sclerosis, disease Huntington’s provide new ideas therapeutic targets that used process. The can summarized follows: (1) motor changes expression levels post-translational modification alteration; (2) microtubules reducing stability disrupting tracks; (3) cargoes diminished binding proteins. Future studies should determine defects disease-specific whether they suitable diseases.
Язык: Английский
Процитировано
15
Frontiers in Physiology, Год журнала: 2021, Номер 12
Опубликована: Июнь 10, 2021
Brain organoids are three-dimensional cultures that contain multiple types of cells and cytoarchitectures, resemble fetal human brain structurally functionally. These being used increasingly to model development disorders, however, they only partially recapitulate such processes, because several limitations, including inability mimic the distinct cortical layers, lack functional neuronal circuitry as well non-neural gyrification, increased cellular stress. Efforts create improved organoid culture systems have led region-specific organoids, vascularized glia-containing assembloids, sliced polarized organoids. Assembloids fused which attempt inter-regional inter-cellular interactions neural by combining regions and/or cell lineages. As a result, assembloids can be subtle aberrations reflect complex neurodevelopmental, neuropsychiatric neurodegenerative disorders. Mammalian organisms possess highly neuroendocrine system, stress whose main task is preservation systemic homeostasis, when latter threatened adverse forces, stressors. The central parts system paraventricular nucleus hypothalamus locus caeruleus/norepinephrine-autonomic nervous nuclei in brainstem; these centers innervate each other interact reciprocally with various CNS structures. Chronic dysregulation has been implicated major pathologies, so-called chronic non-communicable diseases, neuropsychiatric, neurodegenerative, cardiometabolic autoimmune lead significant population morbidity mortality. We speculate could development, regulation better understand stress-related Novel technologies, combined high-throughput single-cell omics gene editing, could, thus, implications for precision medicine.
Язык: Английский
Процитировано
32
World Journal of Psychiatry, Год журнала: 2022, Номер 12(4), С. 541 - 557
Опубликована: Апрель 13, 2022
Schizophrenia (SCZ) is a severe mental illness that affects several brain domains with relation to cognition and behaviour. SCZ symptoms are typically classified into three categories, namely, positive, negative, cognitive. The etiology of thought be multifactorial poorly understood. Accumulating evidence has indicated abnormal synaptic plasticity cognitive impairments in SCZ. Synaptic induced at appropriate synapses during memory formation critical role the Many factors, including structure changes, aberrant expression plasticity-related genes, transmission, may influence play vital roles In this article, we briefly summarize morphology synapse, neurobiology plasticity, review potential mechanisms underlying These abnormalities involve dendritic spines, postsynaptic density, long-term potentiation-like plasticity. We also focus on dysfunction, which reflects impaired connectivity Additionally, targets for treatment discussed article. Therefore, understanding an essential drug therapy.
Язык: Английский
Процитировано
23
Current Medicinal Chemistry, Год журнала: 2022, Номер 30(21), С. 2357 - 2395
Опубликована: Июнь 16, 2022
Abstract: Neurodegenerative and mental disorders are a public health burden with pharma-cological treatments of limited efficacy. Organoselenium compounds receiving great at-tention in medicinal chemistry mainly because their antioxidant immunomodulatory activities, multi-target profile that can favor the treatment multifactorial diseases. Therefore, purpose this review is to discuss recent preclinical studies about orga-noselenium as therapeutic agents for management (e.g., depres-sion, anxiety, bipolar disorder, schizophrenia) neurodegenerative diseases Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis, multiple sclero-sis). We have summarized around 70 peer-reviewed articles from 2016 present used silico, vitro, and/or vivo approaches assess neuropharmacology seleni-um-containing compounds. Among diversity organoselenium molecules investigated last five years, diaryl diselenides, Ebselen-derivatives, Se-containing heterocycles most representative. Ultimately, expected provide disease-oriented information regarding be useful design, synthesis, pharmacological characterization novel bioactive potentially clinically viable candidates.
Язык: Английский
Процитировано
23
Schizophrenia Bulletin, Год журнала: 2023, Номер 49(6), С. 1554 - 1567
Опубликована: Авг. 22, 2023
Abstract Background and Hypothesis Schizophrenia is a multidimensional disease. This study proposes new research framework that combines multimodal meta-analysis genetic/molecular architecture to solve the consistency in neuroimaging biomarkers of schizophrenia whether these link molecular genetics. Study Design We systematically searched Web Science, PubMed, BrainMap for amplitude low-frequency fluctuations (ALFF) or fractional ALFF, regional homogeneity, cerebral blood flow, voxel-based morphometry analysis studies investigating schizophrenia. The pooled-modality, single-modality, illness duration-dependent meta-analyses were performed using activation likelihood estimation algorithm. Subsequently, Spearman correlation partial least squares regression analyses conducted assess relationship between identified reliable convergent patterns multimodality neurotransmitter/transcriptome, prior imaging brain-wide gene expression. Results In total, 203 experiments comprising 10 613 patients 461 healthy controls included. Multimodal showed brain regions significant convergence mainly distributed frontotemporal cortex, anterior cingulate insula, thalamus, striatum, hippocampus. Interestingly, illness-duration subgroups aberrant functional structural evolutionary patterns: Lines from striatum cortical core networks extensive subcortical regions. we found robust abnormalities associated with multiple neurobiological abnormalities, such as dopaminergic, glutamatergic, serotonergic, GABAergic systems. Conclusions work links transcriptome/neurotransmitters signatures underlying disease effects schizophrenia, which provides novel insight into understanding pathophysiology targeted treatments.
Язык: Английский
Процитировано
12