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Frontiers in Psychiatry 2019Of late, evidence emerges that the pathophysiology of psychiatric diseases and their affiliated symptomatologies are at least partly contributable to inflammatory...
Of late, evidence emerges that the pathophysiology of psychiatric diseases and their affiliated symptomatologies are at least partly contributable to inflammatory processes. Also in alcohol use disorders (AUD), this interaction is strongly apparent, with severely immunogenic liver cirrhosis being one of the most critical sequelae of chronic abusive drinking. This somatic immune system activation negatively impacts brain functioning, and additionally, alcohol abuse appears to have a direct detrimental effect on the brain by actively stimulating its immune cells and responses. As cognitive decline majorly contributes to AUD's debility, it is important to know to what extent impairment of cognitive functioning is due to these (neuro-)inflammatory aberrations. We hereby summarize the current existing literature on the interplay between AUD, inflammation, and cognition in a systematic review according to the PRISMA-P guidelines for the systematic review. Although literature on the role of inflammation in alcohol use-related cognitive deficiency remains scarce, current findings indicate that pro-inflammatory processes indeed result in exacerbation of several domains of cognitive deterioration. Interestingly, microglia, the immune cells of the brain, appear to exert initial compensatory neuroprotective functionalities upon acute ethanol exposure while chronic alcohol intake seems to attenuate these responses and overall microglial activity. As these results indicate inflammation to be of importance in cognitive impairment following alcohol consumption and might as such provide alternate therapeutic avenues, a considerable increase in research efforts in this domain is urgently required.
PubMed: 31572234
DOI: 10.3389/fpsyt.2019.00632 -
BioMed Research International 2019Interleukin-6 (IL-6) is a unique cytokine that can play both pro- and anti-inflammatory roles depending on the anatomical site and conditions under which it has been...
Interleukin-6 (IL-6) is a unique cytokine that can play both pro- and anti-inflammatory roles depending on the anatomical site and conditions under which it has been induced. Specific neurons of the hypothalamus provide important signals to control food intake and energy expenditure. In individuals with obesity, a microglia-dependent inflammatory response damages the neural circuits responsible for maintaining whole-body energy homeostasis, resulting in a positive energy balance. However, little is known about the role of IL-6 in the regulation of hypothalamic microglia. In this systematic review, we asked what types of conditions and stimuli could modulate microglial IL-6 expression in murine model. We searched the PubMed and Web of Science databases and analyzed 13 articles that evaluated diverse contexts and study models focused on IL-6 expression and microglia activation, including the effects of stress, hypoxia, infection, neonatal overfeeding and nicotine exposure, lipopolysaccharide stimulus, hormones, exercise protocols, and aging. The results presented in this review emphasized the role of "injury-like" stimuli, under which IL-6 acts as a proinflammatory cytokine, concomitant with marked microglial activation, which drive hypothalamic neuroinflammation. Emerging evidence indicates an important correlation of basal IL-6 levels and microglial function with the maintenance of hypothalamic homeostasis. Advances in our understanding of these different contexts will lead to the development of more specific pharmacological approaches for the management of acute and chronic conditions, like obesity and metabolic diseases, without disturbing the homeostatic functions of IL-6 and microglia in the hypothalamus.
Topics: Animals; Gene Expression Regulation; Humans; Hypothalamus; Interleukin-6; Metabolic Diseases; Mice; Microglia; Obesity
PubMed: 31534953
DOI: 10.1155/2019/1365210 -
Molecular Neuropsychiatry Jun 2019There is tremendous interest in the role of the neuroimmune system and inflammatory processes in substance use disorders (SUDs). Imaging biomarkers of the neuroimmune... (Review)
Review
There is tremendous interest in the role of the neuroimmune system and inflammatory processes in substance use disorders (SUDs). Imaging biomarkers of the neuroimmune system in vivo provide a vital translational bridge between preclinical and clinical research. Herein, we examine two imaging techniques that measure putative indices of the neuroimmune system and review their application among SUDs. Positron emission tomography (PET) imaging of 18 kDa translocator protein availability is a marker associated with microglia. Proton magnetic resonance spectroscopy quantification of inositol levels is a putative glial marker found in astrocytes. Neuroinflammatory responses are initiated and maintained by microglia and astrocytes, and thus represent important imaging markers. The goal of this review is to summarize neuroimaging findings from the substance use literature that report data using these markers and discuss possible mechanisms of action. The extant literature indicates abused substances exert diverse and complex neuroimmune effects. Moreover, drug effects may change across addiction stages, i.e. the neuroimmune effects of acute drug administration may differ from chronic use. This burgeoning field has considerable potential to improve our understanding and treatment of SUDs. Future research is needed to determine how targeting the neuroimmune system may improve treatment outcomes.
PubMed: 31312635
DOI: 10.1159/000499621 -
Croatian Medical Journal Apr 2019To propose potential mechanisms of action of electromagnetic fields (EMF) on astrocytes and microglia and to elucidate the role of heat shock proteins (HSP), adenosine...
AIM
To propose potential mechanisms of action of electromagnetic fields (EMF) on astrocytes and microglia and to elucidate the role of heat shock proteins (HSP), adenosine triphosphate (ATP), calcium ions (Ca2+), and hypoxia-inducible factor 1α (HIF1α) in neurorestoration following the application of EMF.
METHODS
We reviewed the existing studies within the public domain and cross-evaluated their results in order to conclude on the molecular mechanisms of microglia-astrocyte crosstalk at work during EMF treatment.
RESULTS
The existing studies suggest that EMF induces the increase of HSP70 expression and inhibition of HIF1α, thus decreasing inflammation and allowing the microglia-astrocyte crosstalk to initiate the formation of a glial scar within the central nervous system. Furthermore, by potentially up-regulating A2A and A3 adenosine receptors, EMF increases cAMP accumulation from astrocytes and reduces the expression of inflammatory cytokines TNF α and IL-8, thus initiating neurorestoration.
CONCLUSION
The microglia-astrocyte crosstalk during EMF treatment is crucial for the initiation of neurorestoration. Elucidating the exact mechanisms of EMF actions upon microglia and astrocytes, and its role in neurorestoration could be a key step in further research of the therapeutic potential of EMFs in various neurological disorders.
Topics: Adenosine Triphosphate; Animals; Astrocytes; Calcium; Cells, Cultured; Cytokines; Electromagnetic Fields; Heat-Shock Proteins; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Magnetic Field Therapy; Microglia; Neurodegenerative Diseases; Receptor Cross-Talk; Tumor Necrosis Factor-alpha
PubMed: 31044584
DOI: 10.3325/cmj.2019.60.127 -
Translational Psychiatry Nov 2018Increases in the activated state of microglia, the main neuroimmune cells, are widely reported in the brains of patients with neurological and psychiatric disorders.... (Review)
Review
Increases in the activated state of microglia, the main neuroimmune cells, are widely reported in the brains of patients with neurological and psychiatric disorders. Microglia transform from the resting to the activated state by sensing their environment, aided by a variety of ion channels. To examine the effect of ion channels on microglial phenotypes, we conducted a systematic review of immunohistochemical analyses of these neuroimmune cells in animal models following administration of ion channel antagonists, compared to control conditions. A systematic search of the PubMed and Web of Science electronic databases using the PRISMA and WHO methodologies for systematic reviews yielded 15 original peer-reviewed studies. The majority (13 out of 15) of these studies reported a decrease in microglial activated state after ion signaling pharmacological blockade. The studies provide evidence that acute administration of ion channel antagonists leads to a reduction in microglial activation in rodent brains in the models for epilepsy, Parkinson's disease, inflammation, pain, ischemia, and brain and spinal cord injury. Future research should explore microglial-specific druggable targets for neurological and psychiatric disorders. The investigation of acute and chronic administration of ion channel antagonists in microglial phenotypes in primates and the development of microglia-like cells derived from human stem cells could be valuable sources in this direction.
Topics: Animals; Brain; Disease Models, Animal; Humans; Ion Channels; Mental Disorders; Microglia; Nervous System Diseases; Phenotype
PubMed: 30498192
DOI: 10.1038/s41398-018-0318-0 -
CNS Neuroscience & Therapeutics Feb 2019Success in treating patients with atypical parkinsonian syndromes, namely progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD), multiple system atrophy...
AIMS
Success in treating patients with atypical parkinsonian syndromes, namely progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD), multiple system atrophy (MSA), Parkinson's disease with dementia (PDD), and Lewy body dementia with (LBD), remains exceedingly low. The present work overviews the most influential research literature collected on MEDLINE, ISI Web of Science, Cochrane Library, and Scopus for available treatment in atypical parkinsonisms without time restriction.
DISCUSSION
Transdermal rotigotine, autologous mesenchymal stem cells, tideglusib, and coenzyme Q10 along with donepezil, rivastigmine, memantine, and the deep brain stimulation have shown some benefits in alleviating symptoms in APS. Moreover, many new clinical trials are ongoing testing microtubule stabilizer, antitau monoclonal antibody, tau acetylation inhibition, cell replacement, selective serotonin reuptake inhibitor, active immunization, inhibition of toxic α-synuclein oligomers formation, and inhibition of microglia.
CONCLUSION
A detailed knowledge of the pathological mechanism underlying the disorders is needed, and disease-modifying therapies are required to offer better therapeutic options to physician and caregivers of APS patients.
Topics: Adult; Aged; Antiparkinson Agents; Child; Humans; Parkinsonian Disorders
PubMed: 30294976
DOI: 10.1111/cns.13068 -
European Review For Medical and... Jul 2018To evaluate whether Sudden Sensorineural Hearing Loss (S-SNHL) may be an early symptom of Multiple Sclerosis (MS).
OBJECTIVE
To evaluate whether Sudden Sensorineural Hearing Loss (S-SNHL) may be an early symptom of Multiple Sclerosis (MS).
MATERIALS AND METHODS
A systematic review was conducted using the following keywords: "Multiple sclerosis, hearing loss, sudden hearing loss, vertigo, tinnitus, magnetic resonance imaging, otoacoustic emission, auditory brainstem responses, white matter lesions, sensorineural hearing loss, symptoms of MS and otolaryngology, nerve disease and MS". Only the articles that included results of at least one auditory test and MRI were considered. We evaluated the prevalence of SNHL in patients with MS, the presence of different forms of SNHL (S-SNHL and Progressive SNHL (P-SNHL)) and their correlation with the stage of MS, the results of electrophysiological tests, and the location (if any) of MS lesions as detected by white matter hyperintensities in the MRI.
RESULTS
We reviewed a total of 47 articles, which included 29 case reports, 6 prospective studies, 6 cohort studies, 4 case-control studies, and 2 retrospective studies. 25% of patients suffered from SNHL. S-SNHL typically occurred in the early stage of the disease (92% of patients) and was the only presenting symptom in 43% of female subjects. Instead, P-SNHL occurred in the late stage of MS (88% of patients). Auditory Brainstem Responses (ABR) were abnormal in all MS patients with S-SNHL. When S-SNHL appeared during the early stage of the disease, MS lesions were found in the brain in 60% of patients and in the Internal Auditory Canal in 40% of patients. ABR remained abnormal after recovery.
CONCLUSIONS
S-SNHL can be an early manifestation of MS and should always be considered in the differential diagnosis of this condition, especially in women. The pathophysiology can be explained by the involvement of microglia attacking the central and/or peripheral auditory pathways as indicated by WMHs.
Topics: Brain; Early Diagnosis; Hearing Loss, Sudden; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Severity of Illness Index
PubMed: 30058696
DOI: 10.26355/eurrev_201807_15520 -
Iranian Journal of Basic Medical... Dec 2017To determine the molecular and cellular mechanisms of spinal cord regeneration in zebrafish. (Review)
Review
OBJECTIVES
To determine the molecular and cellular mechanisms of spinal cord regeneration in zebrafish.
MATERIALS AND METHODS
Medical databases of PubMed and Scopus were searched with following key words: Zebrafish; spinal cord injuries; regeneration; recovery of function. The map of mechanisms was performed using Xmind software.
RESULTS
Wnt/ß-catenin signaling, L1.1, L1.2, Major vault protein (MVP), contactin-2 and High mobility group box1 (HMGB1) had positive promoting effects on axonal re-growth while Ptena had an inhibitory effect. Neurogenesis is stimulated by Wnt/ß-catenin signaling as well as HMGB1, but inhibited by Notch signaling. Glial cells proliferate in response to fibroblast growth factor (FGF) signaling and Lysophosphatidic acid (LPA). Furthermore, fgf signaling pathway causes glia bridge formation in favor of axonal regeneration. LPA and HMGB1 in acute phase stimulate inflammatory responses around injury and suppress regeneration. LPA also induces microglia activation and neuronal death in addition to glia cell proliferation, but prevents neurite sprouting.
CONCLUSION
This study provides a comprehensive review of the known molecules and mechanisms in the current literature involved in the spinal cord injury (SCI) regeneration in zebrafish, in a time course manner. A better understanding of the whole determining mechanisms for the SCI regeneration should be considered as a main goal for future studies.
PubMed: 29238462
DOI: 10.22038/IJBMS.2017.9620 -
Molecular Psychiatry Feb 2018Neuroinflammation is proposed as one of the mechanisms by which Alzheimer's disease pathology, including amyloid-β plaques, leads to neuronal death and dysfunction....
Neuroinflammation is proposed as one of the mechanisms by which Alzheimer's disease pathology, including amyloid-β plaques, leads to neuronal death and dysfunction. Increases in the expression of markers of microglia, the main neuroinmmune cell, are widely reported in brains from patients with Alzheimer's disease, but the literature has not yet been systematically reviewed to determine whether this is a consistent pathological feature. A systematic search was conducted in Medline, Embase and PsychINFO for articles published up to 23 February 2017. Papers were included if they quantitatively compared microglia markers in post-mortem brain samples from patients with Alzheimer's disease and aged controls without neurological disease. A total of 113 relevant articles were identified. Consistent increases in markers related to activation, such as major histocompatibility complex II (36/43 studies) and cluster of differentiation 68 (17/21 studies), were identified relative to nonneurological aged controls, whereas other common markers that stain both resting and activated microglia, such as ionized calcium-binding adaptor molecule 1 (10/20 studies) and cluster of differentiation 11b (2/5 studies), were not consistently elevated. Studies of ionized calcium-binding adaptor molecule 1 that used cell counts almost uniformly identified no difference relative to control, indicating that increases in activation occurred without an expansion of the total number of microglia. White matter and cerebellum appeared to be more resistant to these increases than other brain regions. Nine studies were identified that included high pathology controls, patients who remained free of dementia despite Alzheimer's disease pathology. The majority (5/9) of these studies reported higher levels of microglial markers in Alzheimer's disease relative to controls, suggesting that these increases are not solely a consequence of Alzheimer's disease pathology. These results show that increased markers of microglia are a consistent feature of Alzheimer's disease, though this seems to be driven primarily by increases in activation-associated markers, as opposed to markers of all microglia.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Autopsy; Biomarkers; Brain; Female; Humans; Male; Microglia; Middle Aged; Plaque, Amyloid; White Matter; tau Proteins
PubMed: 29230021
DOI: 10.1038/mp.2017.246 -
Molecular Neurodegeneration Nov 2017Parkinson's disease (PD) is a progressive movement neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain.... (Review)
Review
Parkinson's disease (PD) is a progressive movement neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, is thought to play an important role in dopaminergic neurotoxicity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are multi-subunit enzymatic complexes that generate reactive oxygen species as their primary function. Increased immunoreactivities for the NADPH oxidases catalytic subunits Nox1, Nox2 and Nox4 have been reported in the brain of PD patients. Furthermore, knockout or genetic inactivation of NADPH oxidases exert a neuroprotective effect and reduce detrimental aspects of pathology in experimental models of the disease. However, the connections between NADPH oxidases and the biological processes believed to contribute to neuronal death are not well known. This review provides a comprehensive summary of our current understanding about expression and physiological function of NADPH oxidases in neurons, microglia and astrocytes and their pathophysiological roles in PD. It summarizes the findings supporting the role of both microglial and neuronal NADPH oxidases in cellular disturbances associated with PD such as neuroinflammation, alpha-synuclein accumulation, mitochondrial and synaptic dysfunction or disruption of the autophagy-lysosome system. Furthermore, this review highlights different steps that are essential for NADPH oxidases enzymatic activity and pinpoints major obstacles to overcome for the development of effective NADPH oxidases inhibitors for PD.
Topics: Animals; Humans; NADPH Oxidases; Parkinson Disease
PubMed: 29132391
DOI: 10.1186/s13024-017-0225-5