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Journal of Neurophysiology Aug 2023Spinal motoneurons contain many ion channels and receptors upon which various cannabinoids are known to act. This scoping review involved the synthesis of evidence from... (Review)
Review
Spinal motoneurons contain many ion channels and receptors upon which various cannabinoids are known to act. This scoping review involved the synthesis of evidence from literature published before August 2022 about the effects of cannabinoids on quantifiable measures of motoneuron output. Four databases (MEDLINE, Embase, PsycINFO, and Web of Science CoreCollection) were queried and 4,237 unique articles were retrieved. Twenty-three studies met the inclusion criteria, and the findings from these studies were grouped according to four emergent themes: rhythmic motoneuron output, afferent feedback integration, membrane excitability, and neuromuscular junction transmission. This synthesis of evidence suggests that CB1 agonists can increase the frequency of cyclical patterns of motoneuron output (i.e., fictive locomotion). Furthermore, a majority of the evidence indicates that activating CB1 receptors at motoneuron synapses promotes excitation of motoneurons by enhancing excitatory synaptic transmission and depressing inhibitory synaptic transmission. The collated study results reveal variable effects of cannabinoids on acetylcholine release at the neuromuscular junction, and the influence of cannabinoids in this area requires more work to ensure precision of findings for CB1 agonist and antagonist impact. Altogether, these reports indicate that the endocannabinoid system is integral within the final common pathway and can impact motor output. This review contributes to understanding the effects of endocannabinoids on synaptic integration at the motoneuron and modulation of motor output.
Topics: Cannabinoids; Motor Neurons; Synapses; Synaptic Transmission; Neuromuscular Junction
PubMed: 37283484
DOI: 10.1152/jn.00460.2022 -
Ochsner Journal 2021Fibromyalgia, a complex disorder that affects 1% to 5% of the population, presents as widespread chronic musculoskeletal pain without physical or laboratory signs of... (Review)
Review
Fibromyalgia, a complex disorder that affects 1% to 5% of the population, presents as widespread chronic musculoskeletal pain without physical or laboratory signs of any specific pathologic process. The mechanism, while still being explored, suggests central sensitization and disordered pain regulation at the spinal cord and supraspinal levels, with a resulting imbalance between excitation and inhibition that may alter central nervous system nociceptive processing. Nociceptive hypersensitivity results from activity of the N-methyl-D-aspartate receptor (NMDAR)-mediated glutamatergic synaptic transmission in the spinal cord and brain. Because ketamine, an NMDAR antagonist, may reduce induction of synaptic plasticity and maintenance of chronic pain states, the study of its use in intravenous form to treat fibromyalgia has increased. We conducted a literature search with the objectives of examining the effect of intravenous ketamine administration on pain relief, identifying side effects, and highlighting the need for clinical studies to evaluate ketamine infusion treatment protocols for patients with fibromyalgia. We used the keywords "fibromyalgia," "chronic pain," "ketamine," "intravenous," and "infusion" and found 7 publications that included 118 patients with fibromyalgia who met inclusion criteria. Clinical studies revealed a short-term reduction-only for a few hours after the infusions-in self-reported pain intensity with single, low-dose, intravenous ketamine infusions, likely attributable to nociception-dependent central sensitization in fibromyalgia via NMDAR blockade. Case studies suggest that increases in the total dose of ketamine and longer, more frequent infusions may be associated with more effective pain relief and longer-lasting analgesia. Another neurotransmitter release may be contributing to this outcome. This systematic review suggests a dose response, indicating potential efficacy of intravenous ketamine in the treatment of fibromyalgia.
PubMed: 34984054
DOI: 10.31486/toj.21.0038 -
Frontiers in Immunology 2021Myasthenia gravis (MG) is an autoimmune disease primarily mediated by acetylcholine receptor antibodies (AChR-Ab), cellular immune dependence, and complement system... (Review)
Review
Myasthenia gravis (MG) is an autoimmune disease primarily mediated by acetylcholine receptor antibodies (AChR-Ab), cellular immune dependence, and complement system involvement. Since the AChR on the postsynaptic membrane is destroyed by an immune attack, sufficient endplate potential cannot be generated, resulting in the development of a synaptic transmission disorder at the neuromuscular junction and in muscle weakness. The role of the complement system in MG has been demonstrated in animal models and clinical tests, and it has been determined that complement inhibition in patients with MG can prevent disease induction and reverse its progression. Eculizumab is a humanized monoclonal antibody that inhibits the cleavage of complement protein C5 and prevents autoimmune damage; additionally, it has received subsequent approval by the Federal Drug Administration of the United States for MG treatment. However, various concerns regarding the use of eculizumab persist. In this review, we have discussed the treatment time, cost effectiveness, long-term efficacy, and tolerability of eculizumab for MG treatment. We have also summarized historical information and have presented perspectives on this new therapeutic modality.
Topics: Animals; Antibodies, Monoclonal, Humanized; Clinical Trials as Topic; Combined Modality Therapy; Complement Inactivating Agents; Complement System Proteins; Disease Management; Disease Susceptibility; Drug Development; Humans; Myasthenia Gravis; Treatment Outcome
PubMed: 34456922
DOI: 10.3389/fimmu.2021.715036 -
American Journal of Obstetrics and... Jan 2023The contribution of genetic factors to the presence of an overactive bladder is recognized. This study aimed to (1) assemble and synthesize available data from studies... (Review)
Review
OBJECTIVE
The contribution of genetic factors to the presence of an overactive bladder is recognized. This study aimed to (1) assemble and synthesize available data from studies assessing differential gene expression in patients with overactive bladder vs controls without overactive bladder and (2) determine possible correlations and functional pathways between genes.
DATA SOURCES
We searched PubMed, Ovid or Medline, and Wiley Cochrane Central Register of Controlled Trials databases between January 1, 2000, and December 15, 2021.
STUDY ELIGIBILITY CRITERIA
Studies were included if gene expression was detected and quantified using molecular approaches performed on human bladder tissue specimens directly and excluded if the gene expression analysis was carried out from blood and urine specimens alone.
METHODS
A systematic review was completed to identify publications that reported differently expressed gene candidates among patients with overactive bladder vs healthy individuals. Gene networking connections and pathway analysis were performed employing Metascape software, where inputs were identified from our systematic review of differentially expressed genes in overactive bladder.
RESULTS
A total of 9 studies were included in the final analysis and 11 genes were identified as being up-regulated (purinergic receptor P2X 2 [P2RX2], smoothelin [SMTN], growth-associated protein 43 [GAP43], transient receptor potential cation channel subfamily M member 8 [TRPM8], cadherin 11 [CDH1], gap junction protein gamma 1 [GJC1], cholinergic receptor muscarinic 2 [CHRM2], cholinergic receptor muscarinic 3 [CHRM3], and transient receptor potential cation channel subfamily V member 4 [TRPV4]) or down-regulated (purinergic receptor P2X 2 [P2RX3] and purinergic receptor P2X 5 [P2RX5]) in patients with overactive bladder. Gene network analysis showed that genes are involved in chemical synaptic transmission, smooth muscle contraction, blood circulation, and response to temperature stimulus. Network analysis demonstrated a significant genetic interaction between TRPV4, TRPM8, P2RX3, and PR2X2 genes.
CONCLUSION
Outcomes of this systematic review highlighted potential biomarkers for treatment efficacy and have laid the groundwork for developing future gene therapies for overactive bladder in clinical settings.
Topics: Humans; Urinary Bladder, Overactive; TRPV Cation Channels; Genetic Markers; Cholinergic Antagonists; Receptors, Cholinergic; Receptors, Purinergic; Receptor, Muscarinic M3
PubMed: 35932882
DOI: 10.1016/j.ajog.2022.07.044 -
Neuroscience and Biobehavioral Reviews Nov 2020The aim of this systematic review was to provide insight in inhibitory control (prepotent response inhibition and interference control) in trauma-exposed youth from a... (Review)
Review
The aim of this systematic review was to provide insight in inhibitory control (prepotent response inhibition and interference control) in trauma-exposed youth from a developmental perspective and exploring the effects of prolonged stress. A systematic search was conducted, resulting in 1722 abstracts. Of those, 33 studies met inclusion criteria. Twelve studies measured prepotent response inhibition (Go/no-go and Stop-signal task), 20 studies measured interference control (Flanker and Stroop task), and one measured both. Some studies indeed found evidence for prolonged trauma exposure impeding both subcomponents of inhibitory control, although others did not. At a later age, inhibitory control problems on task performance seem to disappear. However, distinct patterns of brain activity may suggest that those individuals employ compensation strategies. Together, the findings may suggest that non-specific inhibitory control problems occur after prolonged trauma exposure, with older youth possibly employing compensation strategies on the tasks. Future studies may provide a clearer picture of the compensation strategies and the circumstances in which they become visible.
Topics: Adolescent; Humans; Inhibition, Psychological; Psychomotor Performance; Reaction Time; Synaptic Transmission; Task Performance and Analysis
PubMed: 32574571
DOI: 10.1016/j.neubiorev.2020.06.001 -
Frontiers in Behavioral Neuroscience 2022Kaixinsan (KXS) has been in use as an effective classic formulation of traditional Chinese medicine for depression. However, its active components and action mechanism...
INTRODUCTION
Kaixinsan (KXS) has been in use as an effective classic formulation of traditional Chinese medicine for depression. However, its active components and action mechanism against depression remain elusive. The purpose of this study was to summarize and evaluate the efficacy and potential pharmacological mechanisms of KXS in antidepressant treatment.
MATERIALS AND METHODS
Reports on the use of KXS in the treatment of depression were systematically collected from PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Chongqing VIP, and Wanfang Data from the establishment to July 2022, including those on mood disorders in neurological diseases such as Alzheimer's disease. Meta-analysis was conducted with the Review Manager 5.3 software. Online datasets, traditional Chinese medicine system pharmacological analysis platform, GeneCards, online Mendelian inheritance in man, and DisGeNET were used to investigate the depression-related genes. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments were performed to construct the 'component-target-pathways' network using Metascape online analyses.
RESULT
Ten studies were included in the analysis. Meta-analysis showed that both low-dose KXS (SMD = 19.66, = 7.96, and = 42%) and high-dose KXS (SMD = 23.84, = 8.46, and = 13%) could increase the sucrose preference in depression models. In addition, 5-hydroxytryptamine (5-HT) (SMD = 10.91, = 2.95, and = 50%) returned to normal level after the treatment at low dose KXS. In network pharmacology, 50 active components and 376 gene targets were screened out. AKT1, GAPDH, ALB, TNF, and TP53 were the core target proteins. GO analysis showed that KXS mainly treats depression in biological processes such as response to drugs, cellular calcium ion homeostasis, and regulation of chemical synaptic signal transmission. KEGG results show that the mechanism of action of KXS in treating depression is through neural activity ligand-receptor interaction, the calcium signaling and CAMP signaling pathways.
DISCUSSION
The study reveals the active components and potential molecular mechanism of KXS in the treatment of depression and provides evidence for future basic research.
PubMed: 36560929
DOI: 10.3389/fnbeh.2022.1061877 -
Complex Psychiatry 2023Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and... (Review)
Review
INTRODUCTION
Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and transcriptomic modifications may help to dissect the biological factors underlying the gene-environment interplay in PTSD. To date, most human PTSD epigenetics studies have used peripheral tissue, and these findings have complex and poorly understood relationships to brain alterations. Studies examining brain tissue may help characterize the brain-specific transcriptomic and epigenomic profiles of PTSD. In this review, we compiled and integrated brain-specific molecular findings of PTSD from humans and animals.
METHODS
A systematic literature search according to the PRISMA criteria was performed to identify transcriptomic and epigenomic studies of PTSD, focusing on brain tissue from human postmortem samples or animal-stress paradigms.
RESULTS
Gene- and pathway-level convergence analyses revealed PTSD-dysregulated genes and biological pathways across brain regions and species. A total of 243 genes converged across species, with 17 of them significantly enriched for PTSD. Chemical synaptic transmission and signaling by G-protein-coupled receptors were consistently enriched across omics and species.
DISCUSSION
Our findings point out dysregulated genes highly replicated across PTSD studies in humans and animal models and suggest a potential role for the corticotropin-releasing hormone/orexin pathway in PTSD's pathophysiology. Further, we highlight current knowledge gaps and limitations and recommend future directions to address them.
PubMed: 37404872
DOI: 10.1159/000529536 -
Addiction (Abingdon, England) Sep 2022Genomic and transcriptomic findings greatly broaden the biological knowledge regarding substance use. However, systematic convergence and comparison evidence of...
Common and distinguishing genetic factors for substance use behavior and disorder: an integrated analysis of genomic and transcriptomic studies from both human and animal studies.
BACKGROUND AND AIMS
Genomic and transcriptomic findings greatly broaden the biological knowledge regarding substance use. However, systematic convergence and comparison evidence of genome-wide findings is lacking for substance use. Here, we combined all the genome-wide findings from both substance use behavior and disorder (SUBD) and identified common and distinguishing genetic factors for different SUBDs.
METHODS
Systemic literature search for genome-wide association (GWAS) and RNA-seq studies of alcohol/nicotine/drug use behavior (partially meets or not reported diagnostic criteria) and alcohol use behavior and disorder (AUBD), nicotine use behavior and disorder (NUBD) and drug use behavior and disorder (DUBD) was performed using PubMed and the GWAS catalog. Drug use was focused upon cannabis, opioid, cocaine and methamphetamine use. GWAS studies required case-control or case/cohort samples. RNA-seq studies were based on brain tissues. The genes which contained significant single nucleotide polymorphism (P ≤ 1 × 10 ) in GWAS and reported as significant in RNA-seq studies were extracted. Pathway enrichment was performed by using Metascape. Gene interaction networks were identified by using the Protein Interaction Network Analysis database.
RESULTS
Total SUBD-related 2910 genes were extracted from 75 GWAS studies (2 773 889 participants) and 17 RNA-seq studies. By overlapping the genes and pathways of AUBD, NUBD and DUBD, four shared genes (CACNB2, GRIN2B, PLXDC2 and PKNOX2), four shared pathways [two Gene Ontology (GO) terms of 'modulation of chemical synaptic transmission', 'regulation of trans-synaptic signaling', two Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of 'dopaminergic synapse', 'cocaine addiction'] were identified (significantly higher than random, P < 1 × 10 ). The top shared KEGG pathways (Benjamini-Hochberg-corrected P-value < 0.05) in the pairwise comparison of AUBD versus DUBD, NUBD versus DUBD, AUBD versus NUBD were 'Epstein-Barr virus infection', 'protein processing in endoplasmic reticulum' and 'neuroactive ligand-receptor interaction', respectively. We also identified substance-specific genetic factors: i.e. ADH1B and ALDH2 were unique for AUBD, while CHRNA3 and CHRNA4 were unique for NUBD.
CONCLUSIONS
This systematic review identifies the shared and unique genes and pathways for alcohol, nicotine and drug use behaviors and disorders at the genome-wide level and highlights critical biological processes for the common and distinguishing vulnerability of substance use behaviors and disorders.
Topics: Aldehyde Dehydrogenase, Mitochondrial; Animals; Cocaine; Epstein-Barr Virus Infections; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomics; Herpesvirus 4, Human; Humans; Nicotine; Polymorphism, Single Nucleotide; Substance-Related Disorders; Tobacco Use Disorder; Transcriptome
PubMed: 35491750
DOI: 10.1111/add.15908 -
Antioxidants (Basel, Switzerland) Mar 2024The aging of the global population has increased the prevalence of neurodegenerative conditions. (BM), an herb with active compounds, such as bacosides A and B,... (Review)
Review
Investigating the Neuroprotective and Cognitive-Enhancing Effects of : A Systematic Review Focused on Inflammation, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis.
The aging of the global population has increased the prevalence of neurodegenerative conditions. (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.
PubMed: 38671841
DOI: 10.3390/antiox13040393 -
Frontiers in Neuroendocrinology Apr 2020Endocrine organizational and activational influences on cognitive and affective circuits are likely critical to the development of premenstrual dysphoric disorder...
Endocrine organizational and activational influences on cognitive and affective circuits are likely critical to the development of premenstrual dysphoric disorder (PMDD), a sex-specific hormone-dependent mood disorder. An overview of the anatomical and functional neural characterization of this disorder is presented here by means of neuroimaging correlates, identified from eighteen publications (n = 361 subjects). While white matter integrity remains uninvestigated, greater cerebellar grey matter volume and metabolism were observed in patients with PMDD, along with altered serotonergic and GABAergic neurotransmission. Differential corticolimbic activation in response to emotional stimuli distinguishes the PMDD brain, namely enhanced amygdalar and diminished fronto-cortical function. Thus far, the emotional distress and dysregulation linked to PMDD seem to be defined by structural, chemical and functional brain signatures; however, their characterization remains sparsely studied and somewhat inconsistent. Clear and well-replicated neurobiological features of PMDD are needed to promote timely diagnoses and inform development of prevention and treatment strategies.
Topics: Adult; Brain; Cognition; Emotions; Female; Humans; Magnetic Resonance Imaging; Menstrual Cycle; Neuroimaging; Positron-Emission Tomography; Premenstrual Dysphoric Disorder; Serotonin; Synaptic Transmission; gamma-Aminobutyric Acid
PubMed: 32268180
DOI: 10.1016/j.yfrne.2020.100838