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Toxins Feb 2021AbobotulinumtoxinA (aboBoNT-A) has been used for various cosmetic purposes, including minimization of moderate to severe lines, or other cosmetic indications, in the...
AbobotulinumtoxinA (aboBoNT-A) has been used for various cosmetic purposes, including minimization of moderate to severe lines, or other cosmetic indications, in the face and neck. We carried out a systematic review to identify all relevant evidence on the treatment approaches and outcomes of aboBoNT-A as a cosmetic treatment of the middle and lower areas of the face, and the neck. Embase, MEDLINE, Cochrane Library, congress proceedings and review bibliographies were searched for relevant studies. Identified articles were screened against pre-specified eligibility criteria. Of 560 unique articles identified, 10 were included for data extraction (three observational studies, 1 randomized controlled trial [with two articles] and five non-randomized trials). The articles provided data on gummy/asymmetric smile (2), marionette lines (5), masseter muscle volume (2), nasal wrinkles (2), perioral wrinkles (3) and the platysma muscle (4). All articles reporting on efficacy of aboBoNT-A demonstrated positive results, including reduction of wrinkles (5), reduction of masseter muscle (2) and degree of gummy smile (1) compared with before treatment. No serious adverse events were reported and patient satisfaction was high. In conclusion, positive findings support further research of aboBoNT-A for the middle and lower areas of the face, and in the neck, which are largely unapproved indications.
Topics: Acetylcholine Release Inhibitors; Adolescent; Adult; Aged; Botulinum Toxins, Type A; Cosmetic Techniques; Esthetics; Face; Facial Expression; Female; Humans; Injections; Male; Middle Aged; Neck; Off-Label Use; Patient Satisfaction; Skin Aging; Treatment Outcome; Young Adult
PubMed: 33671800
DOI: 10.3390/toxins13020169 -
International Journal of Chronic... 2021Long-acting muscarinic receptor antagonists (LAMAs) are the cornerstone for the treatment of chronic obstructive pulmonary disease (COPD); furthermore, tiotropium is... (Review)
Review
Long-acting muscarinic receptor antagonists (LAMAs) are the cornerstone for the treatment of chronic obstructive pulmonary disease (COPD); furthermore, tiotropium is approved as add-on therapy in severe asthmatic patients. Accumulating evidence suggests that LAMAs may modulate airway contractility and airway hyperresponsiveness not only by blocking muscarinic acetylcholine receptors (mAchRs) expressed on airway smooth muscle but also via anti-inflammatory mechanisms by blocking mAchRs expressed on inflammatory cells, submucosal glands, and epithelial cells. The aim of this systematic review, performed according to the PRISMA-P guidelines, was to provide a synthesis of the literature on the anti-inflammatory impact of muscarinic receptor antagonists in the airways. Most of the current evidence originates from studies on tiotropium, that demonstrated a reduction in synthesis and release of cytokines and chemokines, as well as the number of total and differential inflammatory cells, induced by different pro-inflammatory stimuli. Conversely, few data are currently available for aclidinium and glycopyrronium, whereas no studies on the potential anti-inflammatory effect of umeclidinium have been reported. Overall, a large body of evidence supports the beneficial impact of tiotropium against airway inflammation. Further well-designed randomized controlled trials are needed to better elucidate the anti-inflammatory mechanisms leading to the protective effect of LAMAs against exacerbations via identifying suitable biomarkers.
Topics: Bronchodilator Agents; Humans; Inflammation; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Receptors, Muscarinic; Tiotropium Bromide
PubMed: 33603353
DOI: 10.2147/COPD.S285867 -
Frontiers in Aging Neuroscience 2020Sarcopenia is an aging process with a decline of skeletal muscle mass and function, which is a challenging public health problem with reduced quality of life in...
Sarcopenia is an aging process with a decline of skeletal muscle mass and function, which is a challenging public health problem with reduced quality of life in patients. The endplate, the post-synaptic part of the neuromuscular junction (NMJ), occupies 0.1% of the myofiber surface area only, but is composed of millions of acetylcholine receptors (AChRs) that are efficient in binding to acetylcholine (ACh) and triggering skeletal muscle contraction. This systematic review aims to examine aging-associated alterations of post-synaptic AChRs, including morphology, function and related gene expression. A systematic literature search was conducted in PubMed, Embase and Web of Science with relevant keywords by two independent reviewers. Original pre-clinical and clinical studies regarding AChRs changes during aging with available full text and written in English were included. Information was extracted from the included studies for further review. In total, 30 articles were included. Various parameters assessing AChRs alterations by radioassay, immunofluorescence, electrophysiology and mechanical test were reported. Endplate fragmentation and denervation were common in old skeletal muscles during aging. To ensure efficient NMJ transmission and force generation, type I or IIb muscle fibers tended to have increased ACh quanta releasing after electrical stimulations, while type IIa muscle fibers tended to have stronger binding between ACh and AChRs, but the overall function of AChRs was reduced during aging. Alterations of AChRs area depended on muscle type, species and the progress of muscle atrophy and type I muscles fibers tended to demonstrate enlarging AChRs areas. Myogenic regulator factors (MRFs) can regulate the expression of AChRs subunits, while decreased MRF4 may lead to expression changes of AChRs subunits during aging. Sarcoglycan-α can delay low-density lipoprotein receptor-related protein 4 (LRP4) degradation. This protein was increased in old muscles but still cannot suppress the degradation of LRP4. Investigating the role of these AChRs-related genes in the process of aging may provide a potential target to treat sarcopenia.
PubMed: 33362532
DOI: 10.3389/fnagi.2020.597811 -
Frontiers in Pharmacology 2020Fatigue, as a complex, multidimensional symptom, is associated with many physical illnesses. C. A. Mey (PG) is an important herbal drug which has been used for...
BACKGROUND
Fatigue, as a complex, multidimensional symptom, is associated with many physical illnesses. C. A. Mey (PG) is an important herbal drug which has been used for benefiting Qi for thousand years. C. A. Mey and its compounds (PGC) possess various pharmacological activities, including anti-fatigue. Here, we conducted a systematic review of both randomized clinical trials (RCTs) and preclinical animal studies to investigate the efficacy and safety of PGC for fatigue.
METHODS
Electronic searches were performed in 7 databases from the time of each database's inception to August 2019. The methodological quality of RCTs was assessed using 7-item checklist recommended by Cochrane Collaboration or by the CAMARADES 10-item quality checklist. All the data were analyzed using Rev-Man 5.3 and Stata SE software.
RESULTS
Eight eligible RCTs and 30 animal studies were identified. The risk of bias scores in RCTs ranged from 4/7 to 7/7, and of animal studies varied from 4/10 to 7/10. Meta-analyses showed that PGC was superior to placebo according to their respective fatigue scales, heart rate recovery, and clinical effect (P < 0.05). There were a similar number of adverse effects between PGC and placebo group (P > 0.05). Meta-analyses showed that PGC can significantly decrease level of blood lactate, blood urea nitrogen, creatine kinase, malondialdehyde, and lactic dehydrogenase in serum, level of malondialdehyde in liver and level of gamma-aminobutyric acid, 5-hydroxytryptamine in brain tissue, and increase swimming time, level of glutathione peroxidase, glucose, superoxide dismutase in serum, level of glycogen and activity of superoxide dismutase, glutathione peroxidase, and catalase in skeletal muscle, level of hepatic glycogen in liver and level of dopamine, acetylcholine in brain tissue, compared with control (P < 0.05). Meta-analyses showed no significant difference in animal body weight between PGC and control (P > 0.05).
CONCLUSION
The present findings supported, to a certain degree, that PGC can be recommended for routine use in fatigue. The possible mechanism of PGC resists fatigue, mainly through antioxidant stress, regulating carbohydrate metabolism, delaying the accumulation of metabolites, promoting mitochondrial function, neuroprotection, antiapoptosis, and regulating neurotransmitter disorder in central nervous system.
PubMed: 32765262
DOI: 10.3389/fphar.2020.01031 -
Orphanet Journal of Rare Diseases Feb 2019Congenital myasthenic syndromes (CMSs) are a genotypically and phenotypically heterogeneous group of neuromuscular disorders, which have in common an impaired...
OBJECTIVES
Congenital myasthenic syndromes (CMSs) are a genotypically and phenotypically heterogeneous group of neuromuscular disorders, which have in common an impaired neuromuscular transmission. Since the field of CMSs is steadily expanding, the present review aimed at summarizing and discussing current knowledge and recent advances concerning the etiology, clinical presentation, diagnosis, and treatment of CMSs.
METHODS
Systematic literature review.
RESULTS
Currently, mutations in 32 genes are made responsible for autosomal dominant or autosomal recessive CMSs. These mutations concern 8 presynaptic, 4 synaptic, 15 post-synaptic, and 5 glycosilation proteins. These proteins function as ion-channels, enzymes, or structural, signalling, sensor, or transporter proteins. The most common causative genes are CHAT, COLQ, RAPSN, CHRNE, DOK7, and GFPT1. Phenotypically, these mutations manifest as abnormal fatigability or permanent or fluctuating weakness of extra-ocular, facial, bulbar, axial, respiratory, or limb muscles, hypotonia, or developmental delay. Cognitive disability, dysmorphism, neuropathy, or epilepsy are rare. Low- or high-frequency repetitive nerve stimulation may show an abnormal increment or decrement, and SF-EMG an increased jitter or blockings. Most CMSs respond favourably to acetylcholine-esterase inhibitors, 3,4-diamino-pyridine, salbutamol, albuterol, ephedrine, fluoxetine, or atracurium.
CONCLUSIONS
CMSs are an increasingly recognised group of genetically transmitted defects, which usually respond favorably to drugs enhancing the neuromuscular transmission. CMSs need to be differentiated from neuromuscular disorders due to muscle or nerve dysfunction.
Topics: Cholinesterase Inhibitors; Humans; Mutation; Myasthenic Syndromes, Congenital; Neuromuscular Agents; Proteins
PubMed: 30808424
DOI: 10.1186/s13023-019-1025-5 -
The Cochrane Database of Systematic... Jun 2018Alzheimer's disease is the most common cause of dementia in older people. One approach to symptomatic treatment of Alzheimer's disease is to enhance cholinergic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alzheimer's disease is the most common cause of dementia in older people. One approach to symptomatic treatment of Alzheimer's disease is to enhance cholinergic neurotransmission in the brain by blocking the action of the enzyme responsible for the breakdown of the neurotransmitter acetylcholine. This can be done by a group of drugs known as cholinesterase inhibitors. Donepezil is a cholinesterase inhibitor.This review is an updated version of a review first published in 1998.
OBJECTIVES
To assess the clinical efficacy and safety of donepezil in people with mild, moderate or severe dementia due to Alzheimer's disease; to compare the efficacy and safety of different doses of donepezil; and to assess the effect of donepezil on healthcare resource use and costs.
SEARCH METHODS
We searched Cochrane Dementia and Cognitive Improvement's Specialized Register, MEDLINE, Embase, PsycINFO and a number of other sources on 20 May 2017 to ensure that the search was as comprehensive and up-to-date as possible. In addition, we contacted members of the Donepezil Study Group and Eisai Inc.
SELECTION CRITERIA
We included all double-blind, randomised controlled trials in which treatment with donepezil was administered to people with mild, moderate or severe dementia due to Alzheimer's disease for 12 weeks or more and its effects compared with those of placebo in a parallel group of patients, or where two different doses of donepezil were compared.
DATA COLLECTION AND ANALYSIS
One reviewer (JSB) extracted data on cognitive function, activities of daily living, behavioural symptoms, global clinical state, quality of life, adverse events, deaths and healthcare resource costs. Where appropriate and possible, we estimated pooled treatment effects. We used GRADE methods to assess the quality of the evidence for each outcome.
MAIN RESULTS
Thirty studies involving 8257 participants met the inclusion criteria of the review, of which 28 studies reported results in sufficient detail for the meta-analyses. Most studies were of six months' duration or less. Only one small trial lasted 52 weeks. The studies tested mainly donepezil capsules at a dose of 5 mg/day or 10 mg/day. Two studies tested a slow-release oral formulation that delivered 23 mg/day. Participants in 21 studies had mild to moderate disease, in five studies moderate to severe, and in four severe disease. Seventeen studies were industry funded or sponsored, four studies were funded independently of industry and for nine studies there was no information on source of funding.Our main analysis compared the safety and efficacy of donepezil 10 mg/day with placebo at 24 to 26 weeks of treatment. Thirteen studies contributed data from 3396 participants to this analysis. Eleven of these studies were multicentre studies. Seven studies recruited patients with mild to moderate Alzheimer's disease, two with moderate to severe, and four with severe Alzheimer's disease, with a mean age of about 75 years. Almost all evidence was of moderate quality, downgraded due to study limitations.After 26 weeks of treatment, donepezil compared with placebo was associated with better outcomes for cognitive function measured with the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog, range 0 to 70) (mean difference (MD) -2.67, 95% confidence interval (CI) -3.31 to -2.02, 1130 participants, 5 studies), the Mini-Mental State Examination (MMSE) score (MD 1.05, 95% CI 0.73 to 1.37, 1757 participants, 7 studies) and the Severe Impairment Battery (SIB, range 0 to 100) (MD 5.92, 95% CI 4.53 to 7.31, 1348 participants, 5 studies). Donepezil was also associated with better function measured with the Alzheimer's Disease Cooperative Study activities of daily living score for severe Alzheimer's disease (ADCS-ADL-sev) (MD 1.03, 95% CI 0.21 to 1.85, 733 participants, 3 studies). A higher proportion of participants treated with donepezil experienced improvement on the clinician-rated global impression of change scale (odds ratio (OR) 1.92, 95% CI 1.54 to 2.39, 1674 participants, 6 studies). There was no difference between donepezil and placebo for behavioural symptoms measured by the Neuropsychiatric Inventory (NPI) (MD -1.62, 95% CI -3.43 to 0.19, 1035 participants, 4 studies) or by the Behavioural Pathology in Alzheimer's Disease (BEHAVE-AD) scale (MD 0.4, 95% CI -1.28 to 2.08, 194 participants, 1 study). There was also no difference between donepezil and placebo for Quality of Life (QoL) (MD -2.79, 95% CI -8.15 to 2.56, 815 participants, 2 studies).Participants receiving donepezil were more likely to withdraw from the studies before the end of treatment (24% versus 20%, OR 1.25, 95% CI 1.05 to 1.50, 2846 participants, 12 studies) or to experience an adverse event during the studies (72% vs 65%, OR 1.59, 95% 1.31 to 1.95, 2500 participants, 10 studies).There was no evidence of a difference between donepezil and placebo for patient total healthcare resource utilisation.Three studies compared donepezil 10 mg/day to donepezil 5 mg/day over 26 weeks. The 5 mg dose was associated with slightly worse cognitive function on the ADAS-Cog, but not on the MMSE or SIB, with slightly better QoL and with fewer adverse events and withdrawals from treatment. Two studies compared donepezil 10 mg/day to donepezil 23 mg/day. There were no differences on efficacy outcomes, but fewer participants on 10 mg/day experienced adverse events or withdrew from treatment.
AUTHORS' CONCLUSIONS
There is moderate-quality evidence that people with mild, moderate or severe dementia due to Alzheimer's disease treated for periods of 12 or 24 weeks with donepezil experience small benefits in cognitive function, activities of daily living and clinician-rated global clinical state. There is some evidence that use of donepezil is neither more nor less expensive compared with placebo when assessing total healthcare resource costs. Benefits on 23 mg/day were no greater than on 10 mg/day, and benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose, but the rates of withdrawal and of adverse events before end of treatment were higher the higher the dose.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Cognition; Cognition Disorders; Donepezil; Humans; Indans; Nootropic Agents; Piperidines; Randomized Controlled Trials as Topic
PubMed: 29923184
DOI: 10.1002/14651858.CD001190.pub3 -
Pharmacogenomics Jul 2018Smoking cessation treatment outcomes may be heavily influenced by genetic variations among smokers. Therefore, identifying specific variants that affect response to...
Smoking cessation treatment outcomes may be heavily influenced by genetic variations among smokers. Therefore, identifying specific variants that affect response to different pharmacotherapies is of major interest to the field. In the current study, we systematically review all studies published in or after the year 1990 which examined one or more gene-drug interactions for smoking cessation treatment. Out of 644 citations, 46 articles met the inclusion criteria for the systematic review. We summarize evidence on several genetic polymorphisms (CHRNA5-A3-B4, CYP2A6, DBH, CHRNA4, COMT, DRD2, DRD4 and CYP2B6) and their potential moderating pharamacotherarpy effects on patient cessation efficacy rates. These findings are promising and call for further research to demonstrate the effectiveness of genetic testing in personalizing treatment decision-making and improving outcome.
Topics: Cytochrome P-450 CYP2A6; Genetic Variation; Humans; Nerve Tissue Proteins; Nicotine; Pharmacogenetics; Receptors, Nicotinic; Smoking; Smoking Cessation; Tobacco Use Disorder
PubMed: 29914292
DOI: 10.2217/pgs-2018-0023 -
The Cochrane Database of Systematic... Oct 2017Attention deficit hyperactivity disorder (ADHD) is a prevalent neurobiological condition, characterised by behavioral and cognitive symptoms such as inattention,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a prevalent neurobiological condition, characterised by behavioral and cognitive symptoms such as inattention, impulsivity and/or excessive activity. The syndrome is commonly accompanied by psychiatric comorbidities and is associated with educational and occupational underachievement.Although psychostimulant medications are the mainstay of treatment for ADHD, not all adults respond optimally to, or can tolerate, these medicines. Thus, alternative non-stimulant treatment approaches for ADHD have been explored. One of these alternatives is bupropion, an aminoketone antidepressant and non-competitive antagonism of nicotinic acetylcholine receptors. Bupropion is registered for the treatment of depression and smoking cessation, but is also used off-label to treat ADHD.
OBJECTIVES
To assess the effects and safety of bupropion for the treatment of adults with ADHD.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and seven other databases in February 2017. We also searched three trials registers and three online theses portals. In addition, we checked references of included studies and contacted study authors to identify potentially relevant studies that were missed by our search.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) that evaluated the effects (including adverse effects) of bupropion compared to placebo in adults with ADHD.
DATA COLLECTION AND ANALYSIS
Two review authors (WV, GB) independently screened records and extracted data using a data extraction sheet that we tested in a pilot study. We extracted all relevant data on study characteristics and results. We assessed risks of bias using the Cochrane 'Risk of bias' tool, and assessed the overall quality of evidence using the GRADE approach. We used a fixed-effect model to pool the results across studies.
MAIN RESULTS
We included six studies with a total of 438 participants. Five studies were conducted in the USA, and one in Iran. All studies evaluated a long-acting version of bupropion, with the dosage ranging from 150 mg up to 450 mg daily. Study intervention length varied from six to 10 weeks. Four studies explicitly excluded participants with psychiatric comorbidity and one study included only participants with opioid dependency. Four studies were funded by industry, but the impact of this on study results is unknown. Two studies were publicly funded and in one of these studies, the lead author was a consultant for several pharmaceutical companies and also received investigator-driven funding from two companies, however none of these companies manufacture bupropion. We judged none of the studies to be free of bias because for most risk of bias domains the study reports failed to provide sufficient details. Using the GRADE approach, we rated the overall quality of evidence as low. We downgraded the quality of the evidence because of serious risk of bias and serious imprecision due to small sample sizes.We found low-quality evidence that bupropion decreased the severity of ADHD symptoms (standardised mean difference -0.50, 95% confidence interval (CI) -0.86 to -0.15, 3 studies, 129 participants), and increased the proportion of participants achieving clinical improvement (risk ratio (RR) 1.50, 95% CI 1.13 to 1.99, 4 studies, 315 participants), and reporting an improvement on the Clinical Global Impression - Improvement scale (RR 1.78, 95% CI 1.27 to 2.50, 5 studies, 337 participants). There was low-quality evidence that the proportion of participants who withdrew due to any adverse effect was similar in the bupropion and placebo groups (RR 1.20, 95% CI 0.35 to 4.10, 3 studies, 253 participants). The results were very similar when using a random-effects model and when we analysed only studies that excluded participants with a psychiatric comorbidity.
AUTHORS' CONCLUSIONS
The findings of this review, which compared bupropion to placebo for adult ADHD, indicate a possible benefit of bupropion. We found low-quality evidence that bupropion decreased the severity of ADHD symptoms and moderately increased the proportion of participants achieving a significant clinical improvement in ADHD symptoms. Furthermore, we found low-quality evidence that the tolerability of bupropion is similar to that of placebo. In the pharmacological treatment of adults with ADHD, extended- or sustained-release bupropion may be an alternative to stimulants. The low-quality evidence indicates uncertainty with respect to the pooled effect estimates. Further research is very likely to change these estimates. More research is needed to reach more definite conclusions as well as clarifying the optimal target population for this medicine. Treatment response remains to be reported in a DSM5-diagnosed population. There is also a lack of knowledge on long-term outcomes.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Bupropion; Central Nervous System Stimulants; Delayed-Action Preparations; Female; Humans; Male; Off-Label Use; Patient Dropouts; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 28965364
DOI: 10.1002/14651858.CD009504.pub2 -
Schizophrenia Bulletin Jul 2017Kynurenic acid (KYNA) is an endogenous antagonist of N-methyl-D-aspartate and α7 nicotinic acetylcholine receptors that is derived from astrocytes as part of the... (Meta-Analysis)
Meta-Analysis Review
Kynurenic acid (KYNA) is an endogenous antagonist of N-methyl-D-aspartate and α7 nicotinic acetylcholine receptors that is derived from astrocytes as part of the kynurenine pathway of tryptophan degradation. Evidence suggests that abnormal KYNA levels are involved in the pathophysiology of schizophrenia. However, this has never been assessed through a meta-analysis. A literature search was conducted through Ovid using Embase, Medline, and PsycINFO databases (last search: December 2016) with the search terms: (kynuren* or KYNA) and (schizophreni* or psychosis). English language studies measuring KYNA levels using any method in patients with schizophrenia and healthy controls (HCs) were identified. Standardized mean differences (SMDs) were calculated to determine differences in KYNA levels between groups. Subgroup analyses were separately performed for nonoverlapping participant samples, KYNA measurement techniques, and KYNA sample source. The influences of patients' age, antipsychotic status (%medicated), and sex (%male) on study SMDs were assessed through a meta-regression. Thirteen studies were deemed eligible for inclusion in the meta-analysis. In the main analysis, KYNA levels were elevated in the patient group. Subgroup analyses demonstrated that KYNA levels were increased in nonoverlapping participant samples, and centrally (cerebrospinal fluid and brain tissue) but not peripherally. Patients' age, %medicated, and %male were each positively associated with study SMDs. Overall, KYNA levels are increased in patients with schizophrenia, specifically within the central nervous system. An improved understanding of KYNA in patients with schizophrenia may contribute to the development of novel diagnostic approaches and therapeutic strategies.
Topics: Adult; Female; Humans; Kynurenic Acid; Male; Schizophrenia
PubMed: 28187219
DOI: 10.1093/schbul/sbw221 -
Frontiers in Cellular Neuroscience 2016Oligodendrogenesis and oligodendrocyte precursor maturation are essential processes during the course of central nervous system development, and lead to the myelination... (Review)
Review
Oligodendrogenesis and oligodendrocyte precursor maturation are essential processes during the course of central nervous system development, and lead to the myelination of axons. Cells of the oligodendrocyte lineage are generated in the germinal zone from migratory bipolar oligodendrocyte precursor cells (OPCs), and acquire cell surface markers as they mature and respond specifically to factors which regulate proliferation, migration, differentiation, and survival. Loss of myelin underlies a wide range of neurological disorders, some of an autoimmune nature-multiple sclerosis probably being the most prominent. Current therapies are based on the use of immunomodulatory agents which are likely to promote myelin repair (remyelination) indirectly by subverting the inflammatory response, aspects of which impair the differentiation of OPCs. Cells of the oligodendrocyte lineage express and are capable of responding to a diverse array of ligand-receptor pairs, including neurotransmitters and nuclear receptors such as γ-aminobutyric acid, glutamate, adenosine triphosphate, serotonin, acetylcholine, nitric oxide, opioids, prostaglandins, prolactin, and cannabinoids. The intent of this review is to provide the reader with a synopsis of our present state of knowledge concerning the pharmacological properties of the oligodendrocyte lineage, with particular attention to these receptor-ligand (i.e., neurotransmitters and nuclear receptor) interactions that can influence oligodendrocyte migration, proliferation, differentiation, and myelination, and an appraisal of their therapeutic potential. For example, many promising mediators work through Ca(2+) signaling, and the balance between Ca(2+) influx and efflux can determine the temporal and spatial properties of oligodendrocytes (OLs). Moreover, Ca(2+) signaling in OPCs can influence not only differentiation and myelination, but also process extension and migration, as well as cell death in mature mouse OLs. There is also evidence that oligodendroglia exhibit Ca(2+) transients in response to electrical activity of axons for activity-dependent myelination. Cholinergic antagonists, as well as endocannabinoid-related lipid-signaling molecules target OLs. An understanding of such pharmacological pathways may thus lay the foundation to allow its leverage for therapeutic benefit in diseases of demyelination.
PubMed: 26903812
DOI: 10.3389/fncel.2016.00027