scholarly journals Corticosterone Induces HMGB1 Release in Primary Cultured Rat Cortical Astrocytes: Involvement of Pannexin-1 and P2X7 Receptor-Dependent Mechanisms

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1068 ◽  
Author(s):  
Kazue Hisaoka-Nakashima ◽  
Honami Azuma ◽  
Fumina Ishikawa ◽  
Yoki Nakamura ◽  
Dengli Wang ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Glucocorticoid Receptors ◽  
High Mobility ◽  
Major Depressive ◽  
P2x7 Receptors ◽  
Pannexin 1 ◽  
Cortical Astrocytes ◽  
Extracellular Release ◽  
The Central Nervous System ◽  
Corticosterone Treatment

A major risk factor for major depressive disorder (MDD) is stress. Stress leads to the release of high-mobility group box-1 (HMGB1), which in turn leads to neuroinflammation, a potential pathophysiological basis of MDD. The mechanism underlying stress-induced HMGB1 release is not known, but stress-associated glucocorticoids could be involved. To test this, rat primary cultured cortical astrocytes, the most abundant cell type in the central nervous system (CNS), were treated with corticosterone and HMGB1 release was assessed by Western blotting and ELISA. Significant HMGB1 was released with treatment with either corticosterone or dexamethasone, a synthetic glucocorticoid. HMGB1 translocated from the nucleus to the cytoplasm following corticosterone treatment. HMGB1 release was significantly attenuated with glucocorticoid receptor blocking. In addition, inhibition of pannexin-1, and P2X7 receptors led to a significant decrease in corticosterone-induced HMGB1 release. Taken together, corticosterone stimulates astrocytic glucocorticoid receptors and triggers cytoplasmic translocation and extracellular release of nuclear HMGB1 through a mechanism involving pannexin-1 and P2X7 receptors. Thus, under conditions of stress, glucocorticoids induce astrocytic HMGB1 release, leading to a neuroinflammatory state that could mediate neurological disorders such as MDD.

scholarly journals Mitochondrial DNA Heteroplasmy as an Informational Reservoir Dynamically Linked to Metabolic and Immunological Processes Associated with COVID-19 Neurological Disorders

2021 ◽  
Author(s):  
George B. Stefano ◽  
Richard M. Kream
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Function ◽  
Neurological Disorders ◽  
Nuclear Dna ◽  
Mitochondrial Dynamics ◽  
Cell Types ◽  
Tissue Specific ◽  
Copy Numbers ◽  
The Central Nervous System ◽  
Mitochondrial Dna Heteroplasmy

AbstractMitochondrial DNA (mtDNA) heteroplasmy is the dynamically determined co-expression of wild type (WT) inherited polymorphisms and collective time-dependent somatic mutations within individual mtDNA genomes. The temporal expression and distribution of cell-specific and tissue-specific mtDNA heteroplasmy in healthy individuals may be functionally associated with intracellular mitochondrial signaling pathways and nuclear DNA gene expression. The maintenance of endogenously regulated tissue-specific copy numbers of heteroplasmic mtDNA may represent a sensitive biomarker of homeostasis of mitochondrial dynamics, metabolic integrity, and immune competence. Myeloid cells, monocytes, macrophages, and antigen-presenting dendritic cells undergo programmed changes in mitochondrial metabolism according to innate and adaptive immunological processes. In the central nervous system (CNS), the polarization of activated microglial cells is dependent on strategically programmed changes in mitochondrial function. Therefore, variations in heteroplasmic mtDNA copy numbers may have functional consequences in metabolically competent mitochondria in innate and adaptive immune processes involving the CNS. Recently, altered mitochondrial function has been demonstrated in the progression of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Accordingly, our review is organized to present convergent lines of empirical evidence that potentially link expression of mtDNA heteroplasmy by functionally interactive CNS cell types to the extent and severity of acute and chronic post-COVID-19 neurological disorders.

scholarly journals Genetic Approaches Using Zebrafish to Study the Microbiota–Gut–Brain Axis in Neurological Disorders

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 566
Author(s):  
Jae-Geun Lee ◽  
Hyun-Ju Cho ◽  
Yun-Mi Jeong ◽  
Jeong-Soo Lee
Keyword(s):  
Neurological Disorders ◽  
Genetic Model ◽  
Molecular Genetic ◽  
Autism Spectrum ◽  
Behavioral Abnormalities ◽  
Bidirectional Signaling ◽  
Intestinal Dysbiosis ◽  
The Central Nervous System ◽  
The Brain

The microbiota–gut–brain axis (MGBA) is a bidirectional signaling pathway mediating the interaction of the microbiota, the intestine, and the central nervous system. While the MGBA plays a pivotal role in normal development and physiology of the nervous and gastrointestinal system of the host, its dysfunction has been strongly implicated in neurological disorders, where intestinal dysbiosis and derived metabolites cause barrier permeability defects and elicit local inflammation of the gastrointestinal tract, concomitant with increased pro-inflammatory cytokines, mobilization and infiltration of immune cells into the brain, and the dysregulated activation of the vagus nerve, culminating in neuroinflammation and neuronal dysfunction of the brain and behavioral abnormalities. In this topical review, we summarize recent findings in human and animal models regarding the roles of the MGBA in physiological and neuropathological conditions, and discuss the molecular, genetic, and neurobehavioral characteristics of zebrafish as an animal model to study the MGBA. The exploitation of zebrafish as an amenable genetic model combined with in vivo imaging capabilities and gnotobiotic approaches at the whole organism level may reveal novel mechanistic insights into microbiota–gut–brain interactions, especially in the context of neurological disorders such as autism spectrum disorder and Alzheimer’s disease.

scholarly journals Meningitis Caused by Salmonella Newport in a Five-Year-Old Child

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Ana De Malet ◽  
Sheila Ingerto ◽  
Israel Gañán
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Invasive Disease ◽  
Salmonella Typhi ◽  
Gram Negative ◽  
Negative Bacillus ◽  
Salmonella Newport ◽  
Gram Negative Bacillus ◽  
The Central Nervous System

Salmonella Newport is a Gram-negative bacillus belonging to the Enterobacteria family and the nontyphi Salmonella (NTS), usually related to gastroenteritis. Main difference between NTS and Salmonella typhi is that the last one evolves to an invasive disease easier than NTS. These can progress to bacteremias in around 5% of cases and secondary focuses can appear occasionally, as in meningitis. An infection of the central nervous system is uncommon, considering its incidence in 0.6–8% of the cases; most of them are described in developing countries and mainly in childhood, especially neonates. Bacterial meningitis by NTS mostly affects immunosuppressed people in Europe. Prognosis is adverse, with a 50% mortality rate, mainly due to complications of infection: hydrocephalus, ventriculitis, abscesses, subdural empyema, or stroke. Choice antibiotic treatments are cefotaxime, ceftriaxone, or ceftazidime. The aim of this paper is to present a case of meningitis caused by Salmonella Newport diagnosed in a five-year-old girl living in a rural area of the province of Ourense (Spain), with favorable evolution and without neurological disorders.

scholarly journals Intestinal Microbiota as an Alternative Therapeutic Target for Epilepsy

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Jiaying Wu ◽  
Yuyu Zhang ◽  
Hongyu Yang ◽  
Yuefeng Rao ◽  
Jing Miao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intestinal Microbiota ◽  
Neurological Disorders ◽  
Digestive System ◽  
Hygiene Hypothesis ◽  
Host Susceptibility ◽  
Immune Disorders ◽  
The Central Nervous System ◽  
Symbiotic Microbiota

Epilepsy is one of the most widespread serious neurological disorders, and an aetiological explanation has not been fully identified. In recent decades, a growing body of evidence has highlighted the influential role of autoimmune mechanisms in the progression of epilepsy. The hygiene hypothesis draws people’s attention to the association between gut microbes and the onset of multiple immune disorders. It is also believed that, in addition to influencing digestive system function, symbiotic microbiota can bidirectionally and reversibly impact the programming of extraintestinal pathogenic immune responses during autoimmunity. Herein, we investigate the concept that the diversity of parasitifer sensitivity to commensal microbes and the specific constitution of the intestinal microbiota might impact host susceptibility to epilepsy through promotion of Th17 cell populations in the central nervous system (CNS).

scholarly journals Microglia Proliferation Is Controlled by P2X7 Receptors in a Pannexin-1-Independent Manner during Early Embryonic Spinal Cord Invasion

2012 ◽  
Vol 32 (34) ◽  
pp. 11559-11573 ◽  
Author(s):  
C. Rigato ◽  
N. Swinnen ◽  
R. Buckinx ◽  
I. Couillin ◽  
J.-M. Mangin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
P2x7 Receptors ◽  
Independent Manner ◽  
Pannexin 1 ◽  
Embryonic Spinal Cord

scholarly journals Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

2017 ◽  
Vol 2017 ◽  
pp. 1-25 ◽  
Author(s):  
Viviana I. Torres ◽  
Daniela Vallejo ◽  
Nibaldo C. Inestrosa
Keyword(s):  
Central Nervous System ◽  
Neurological Disorders ◽  
Neuronal Development ◽  
Protein Complexes ◽  
Synaptic Proteins ◽  
Excitatory Synapses ◽  
Complex Structures ◽  
Disease Phenotype ◽  
The Central Nervous System ◽  
Invertebrate Models

Synapses are complex structures that allow communication between neurons in the central nervous system. Studies conducted in vertebrate and invertebrate models have contributed to the knowledge of the function of synaptic proteins. The functional synapse requires numerous protein complexes with specialized functions that are regulated in space and time to allow synaptic plasticity. However, their interplay during neuronal development, learning, and memory is poorly understood. Accumulating evidence links synapse proteins to neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. In this review, we describe the way in which several proteins that participate in cell adhesion, scaffolding, exocytosis, and neurotransmitter reception from presynaptic and postsynaptic compartments, mainly from excitatory synapses, have been associated with several synaptopathies, and we relate their functions to the disease phenotype.

scholarly journals Functional Coupling between the P2X7 Receptor and Pannexin-1 Channel in Rat Trigeminal Ganglion Neurons

2021 ◽  
Vol 22 (11) ◽  
pp. 5978
Author(s):  
Hiroyuki Inoue ◽  
Hidetaka Kuroda ◽  
Wataru Ofusa ◽  
Sadao Oyama ◽  
Maki Kimura ◽  
...  
Keyword(s):  
Trigeminal Ganglion ◽  
P2x7 Receptor ◽  
P2x Receptor ◽  
Functional Coupling ◽  
Dependent Manner ◽  
High Concentration ◽  
Receptor Antagonists ◽  
P2x7 Receptors ◽  
Pannexin 1 ◽  
Ganglion Neurons

The ionotropic P2X receptor, P2X7, is believed to regulate and/or generate nociceptive pain, and pain in several neuropathological diseases. Although there is a known relationship between P2X7 receptor activity and pain sensing, its detailed functional properties in trigeminal ganglion (TG) neurons remains unclear. We examined the electrophysiological and pharmacological characteristics of the P2X7 receptor and its functional coupling with other P2X receptors and pannexin-1 (PANX1) channels in primary cultured rat TG neurons, using whole-cell patch-clamp recordings. Application of ATP and Bz-ATP induced long-lasting biphasic inward currents that were more sensitive to extracellular Bz-ATP than ATP, indicating that the current was carried by P2X7 receptors. While the biphasic current densities of the first and second components were increased by Bz-ATP in a concentration dependent manner; current duration was only affected in the second component. These currents were significantly inhibited by P2X7 receptor antagonists, while only the second component was inhibited by P2X1, 3, and 4 receptor antagonists, PANX1 channel inhibitors, and extracellular ATPase. Taken together, our data suggests that autocrine or paracrine signaling via the P2X7-PANX1-P2X receptor/channel complex may play important roles in several pain sensing pathways via long-lasting neuronal activity driven by extracellular high-concentration ATP following tissue damage in the orofacial area.

Intake of Anti-Epileptic Drugs and their Influences on Sexual Dysfunctions

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Roheela Yasmeen ◽  
Nida Mobeen ◽  
Muhammad Amjad Khan ◽  
Irfan Aslam ◽  
Samia Chaudhry
Keyword(s):  
Quality Of Life ◽  
Sexual Dysfunction ◽  
Neurological Disorders ◽  
Penile Erection ◽  
The Central Nervous System ◽  
Relationship Of ◽  
The Relationship ◽  
The Brain ◽  
Psychiatric Problems

Epilepsy which is also called seizures disorder is an uncontrolled action of the central nervous system. Itis not a single disease but a set of neurological disorders. Actually in this situation, the brain does notreceive a precise signal and as a result an abnormal condition is produced that is usually involuntary inaction. In this review, we aimed to focus on the relationship of anti-epileptic drugs with sexual dysfunctionand adaptation of better remedies that improve a patient’s family life. Sexual dysfunction is a commoncomorbidity in people with epilepsy which badly affects their quality of life. Sexual dysfunction is causedby different factors like psychiatric problems, anti-epileptic drugs (AEDs) and social factors etc. Sexualdysfunctions include ejaculatory failure, lessen libido, penile erection in men and irregular menstrual cyclein women. Common drugs such as Topiramate, Gabapentin (GBP), Valproate (VA), Carbamazepine (CBZ),Olanzapine (OL) and Risperidone (RTG) that are in practice to treat epilepsy usually produced adverseeffect on sexual dysfunction. Even though a lot of studies have been carried out to control sexualdysfunction in epilepsy’s patient, but still research is going on. Medicine such as Cyproheptadine,Mianserin, Buspirone, Yohimbine were found better to treat epilepsy with minimum side effects of sexualdysfunction. Moreover, it is also seen that certain vasodilators, folate , and vitamin supplements areeffective in improving the quality of life.

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