scholarly journals NG2 glia regulate brain innate immunity via TGF-β2/TGFBR2 axis

BMC Medicine ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Shu-zhen Zhang ◽  
Qin-qin Wang ◽  
Qiao-qiao Yang ◽  
Huan-yu Gu ◽  
Yan-qing Yin ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Diphtheria Toxin ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Normal Brain ◽  
Sequencing Analysis ◽  
Brain Functions ◽  
Lps Challenge ◽  
The Impact ◽  
The Brain

Abstract Background Brain innate immunity is vital for maintaining normal brain functions. Immune homeostatic imbalances play pivotal roles in the pathogenesis of neurological diseases including Parkinson’s disease (PD). However, the molecular and cellular mechanisms underlying the regulation of brain innate immunity and their significance in PD pathogenesis are still largely unknown. Methods Cre-inducible diphtheria toxin receptor (iDTR) and diphtheria toxin-mediated cell ablation was performed to investigate the impact of neuron-glial antigen 2 (NG2) glia on the brain innate immunity. RNA sequencing analysis was carried out to identify differentially expressed genes in mouse brain with ablated NG2 glia and lipopolysaccharide (LPS) challenge. Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were used to evaluate neuroinflammatory response in the presence or absence of NG2 glia. The survival of dopaminergic neurons or glial cell activation was evaluated by immunohistochemistry. Co-cultures of NG2 glia and microglia were used to examine the influence of NG2 glia to microglial activation. Results We show that NG2 glia are required for the maintenance of immune homeostasis in the brain via transforming growth factor-β2 (TGF-β2)-TGF-β type II receptor (TGFBR2)-CX3C chemokine receptor 1 (CX3CR1) signaling, which suppresses the activation of microglia. We demonstrate that mice with ablated NG2 glia display a profound downregulation of the expression of microglia-specific signature genes and remarkable inflammatory response in the brain following exposure to endotoxin lipopolysaccharides. Gain- or loss-of-function studies show that NG2 glia-derived TGF-β2 and its receptor TGFBR2 in microglia are key regulators of the CX3CR1-modulated immune response. Furthermore, deficiency of NG2 glia contributes to neuroinflammation and nigral dopaminergic neuron loss in MPTP-induced mouse PD model. Conclusions These findings suggest that NG2 glia play a critical role in modulation of neuroinflammation and provide a compelling rationale for the development of new therapeutics for neurological disorders.

scholarly journals ATF3 Protects against LPS-Induced Inflammation in Mice via Inhibiting HMGB1 Expression

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Pei-Fang Lai ◽  
Ching-Feng Cheng ◽  
Heng Lin ◽  
Tzu-Ling Tseng ◽  
Hsi-Hsien Chen ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Gene Knockout ◽  
Critical Role ◽  
Negative Regulator ◽  
Tlr4 Signaling ◽  
Lps Challenge ◽  
Hmgb1 Expression ◽  
Elevated Expression ◽  
Sepsis Therapy

Lipopolysaccharide (LPS) triggers innate immunity mainly via TLR4 signaling. ATF3 is a negative regulator of TLR4 signaling. HMGB1 plays a critical role in the final step of sepsis. However, the mechanisms of ATF3 and the role of HMGB1 in regulating innate immunity-induced sepsis are incompletely understood. In this study, we found that serum HMGB1 levels were 10-fold higher in patients with sepsis than normal controls. We further demonstrated that ATF3 gene knockout in mice subjected to LPS-induced endotoxemia correlates with an increase in the mortality rate and the elevated expression of IL-6, TNF-α, NO, MCP-1, and HMGB1 in the lung tissues or serum. The biochemical effects of ATF3 were observed inin vitromacrophages and blocked by ATF3 siRNA treatment. We have also shown that adeno-associated virus-mediated ATF3 gene transfer protected ATF3 knockout mice from LPS-induced mortality. In addition, ATF3 knockdown increased LPS-induced release of HMGB1. In conclusion, upregulation of ATF3 contributes to the reduced release of inflammatory molecules, especially HMGB1, which induced lung injury and increased the survival rate of mice after LPS challenge. Therefore, suppressing LPS-induced inflammation with ATF3 induction or ATF3 mimetics may be an important strategy for sepsis therapy.

scholarly journals Regulatory Roles of Bone in Neurodegenerative Diseases

2020 ◽  
Vol 12 ◽  
Author(s):  
Zhengran Yu ◽  
Zemin Ling ◽  
Lin Lu ◽  
Jin Zhao ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
The Elderly ◽  
Lymphoid Organ ◽  
The Body ◽  
Hematopoietic Stem ◽  
Brain Functions ◽  
And Function ◽  
The Impact ◽  
The Brain

Osteoporosis and neurodegenerative diseases are two kinds of common disorders of the elderly, which often co-occur. Previous studies have shown the skeletal and central nervous systems are closely related to pathophysiology. As the main structural scaffold of the body, the bone is also a reservoir for stem cells, a primary lymphoid organ, and an important endocrine organ. It can interact with the brain through various bone-derived cells, mostly the mesenchymal and hematopoietic stem cells (HSCs). The bone marrow is also a place for generating immune cells, which could greatly influence brain functions. Finally, the proteins secreted by bones (osteokines) also play important roles in the growth and function of the brain. This article reviews the latest research studying the impact of bone-derived cells, bone-controlled immune system, and bone-secreted proteins on the brain, and evaluates how these factors are implicated in the progress of neurodegenerative diseases and their potential use in the diagnosis and treatment of these diseases.

scholarly journals The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 435 ◽  
Author(s):  
Anna Winiarska-Mieczan ◽  
Ewa Baranowska-Wójcik ◽  
Małgorzata Kwiecień ◽  
Eugeniusz R. Grela ◽  
Dominik Szwajgier ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Negative Impact ◽  
Functional Disorders ◽  
Brain Functions ◽  
Diet Supplements ◽  
The Impact ◽  
The Brain ◽  
All Diseases

Neurodegenerative diseases are progressive diseases of the nervous system that lead to neuron loss or functional disorders. Neurodegenerative diseases require long-term, sometimes life-long pharmacological treatment, which increases the risk of adverse effects and a negative impact of pharmaceuticals on the patients’ general condition. One of the main problems related to the treatment of this type of condition is the limited ability to deliver drugs to the brain due to their poor solubility, low bioavailability, and the effects of the blood-brain barrier. Given the above, one of the main objectives of contemporary scientific research focuses on the prevention of neurodegenerative diseases. As disorders related to the competence of the antioxidative system are a marker in all diseases of this type, the primary prophylactics should entail the use of exogenous antioxidants, particularly ones that can be used over extended periods, regardless of the patient’s age, and that are easily available, e.g., as part of a diet or as diet supplements. The paper analyzes the significance of the oxidoreductive balance in the pathogenesis of neurodegenerative diseases. Based on information published globally in the last 10 years, an analysis is also provided with regard to the impact of exogenous antioxidants on brain functions with respect to the prevention of this type of diseases.

scholarly journals Cholesterol: Its Regulation and Role in Central Nervous System Disorders

Cholesterol ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-19 ◽  
Author(s):  
Matthias Orth ◽  
Stefano Bellosta
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Metabolic Pathways ◽  
Cholesterol Metabolism ◽  
Major Constituent ◽  
Normal Brain ◽  
Lipoprotein Receptors ◽  
Brain Cholesterol ◽  
Brain Functions ◽  
The Brain

Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer’s disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules). We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions.

Effects of Small-World Rewiring Probability and Noisy Synaptic Conductivity on Slow Waves: Cortical Network

2017 ◽  
Vol 29 (3) ◽  
pp. 679-715
Author(s):  
Ramazan Tekin ◽  
Mehmet Emin Tagluk
Keyword(s):  
Critical Role ◽  
Small World ◽  
Cortical Network ◽  
Abnormal Development ◽  
Oscillatory Activity ◽  
Normal Brain ◽  
Brain Functions ◽  
Functional Development ◽  
Two Parameters ◽  
The Waves

Physiological rhythms play a critical role in the functional development of living beings. Many biological functions are executed with an interaction of rhythms produced by internal characteristics of scores of cells. While synchronized oscillations may be associated with normal brain functions, anomalies in these oscillations may cause or relate the emergence of some neurological or neuropsychological pathologies. This study was designed to investigate the effects of topological structure and synaptic conductivity noise on the spatial synchronization and temporal rhythmicity of the waves generated by cells in the network. Because of holding the ability of clustering and randomizing with change of parameters, small-world (SW) network topology was chosen. The oscillatory activity of network was tried out by manipulating an insulated SW, cortical network model whose morphology is very close to real world. According to the obtained results, it was observed that at the optimal probabilistic rates of conductivity noise and rewiring of SW, powerful synchronized oscillatory small waves are generated in relation to the internal dynamics of cells, which are in line with the network’s input. These two parameters were observed to be quite effective on the excitation-inhibition balance of the network. Accordingly, it may be suggested that the topological dynamics of SW and noisy synaptic conductivity may be associated with the normal and abnormal development of neurobiological structure.

scholarly journals Brain Physiology and Pathophysiology in Mental Stress

2013 ◽  
Vol 2013 ◽  
pp. 1-23 ◽  
Author(s):  
Karim Alkadhi
Keyword(s):  
Signal Transduction ◽  
Learning And Memory ◽  
Mental Stress ◽  
Negative Effects ◽  
Functional Changes ◽  
Brain Physiology ◽  
Brain Functions ◽  
Brain Structure And Function ◽  
The Impact ◽  
The Brain

Exposure to various forms of stress is a common daily occurrence in the lives of most individuals, with both positive and negative effects on brain function. The impact of stress is strongly influenced by the type and duration of the stressor. In its acute form, stress may be a necessary adaptive mechanism for survival and with only transient changes within the brain. However, severe and/or prolonged stress causes overactivation and dysregulation of the hypothalamic pituitary adrenal (HPA) axis thus inflicting detrimental changes in the brain structure and function. Therefore, chronic stress is often considered a negative modulator of the cognitive functions including the learning and memory processes. Exposure to long-lasting stress diminishes health and increases vulnerability to mental disorders. In addition, stress exacerbates functional changes associated with various brain disorders including Alzheimer’s disease and Parkinson’s disease. The primary purpose of this paper is to provide an overview for neuroscientists who are seeking a concise account of the effects of stress on learning and memory and associated signal transduction mechanisms. This review discusses chronic mental stress and its detrimental effects on various aspects of brain functions including learning and memory, synaptic plasticity, and cognition-related signaling enabled via key signal transduction molecules.

scholarly journals The Possible Role Of Toll-Like Receptor 4 In The Pathology Of Stroke

2017 ◽  
pp. 8
Author(s):  
Mohammad Allahtavakoli ◽  
Ali Shamsizadeh ◽  
Ali Roohbakhsh ◽  
Amir Moghadam-Ahmadi ◽  
Mohammad Reza Rahmani ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Inflammatory Response ◽  
System Response ◽  
Toll Like Receptor ◽  
Key Factors ◽  
Toll Like Receptor 4 ◽  
Brain Functions ◽  
Essential Components ◽  
The Impact

Stroke is a prevalent and dangerous health problem, which triggers an intense inflammatory response to Toll-like receptors (TLRs) activation. TLRs are the essential components of innate immunity system response, and therefore, they are one of the key factors involved in recognizing pathogens and internal ligands. Among TLRs, TLR4 significantly participates in the induction of inflammation and brain functions, hence, it has been hypothesized that this molecule is associated with several brain immune-related diseases such as stroke. It has also been proved that animals with TLR4 deficiency have higher protection against ischemia and the absence of TLR4 reduces the neuroinflammation and injuries associated with brain trauma. TLR4 deficiency may play a neuroprotective role in the occurrence of stroke. This article will review recent information regarding the impact of TLR4 in the pathogenicity of stroke.

scholarly journals Characterization of Brain Iron Deposition Pattern and Its Association With Genetic Risk Factor in Alzheimer’s Disease Using Susceptibility-Weighted Imaging

2021 ◽  
Vol 15 ◽  
Author(s):  
Peiting You ◽  
Xiang Li ◽  
Zhijiang Wang ◽  
Huali Wang ◽  
Bin Dong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Studies ◽  
Iron Deposition ◽  
Susceptibility Weighted Imaging ◽  
Normal Brain ◽  
Brain Iron ◽  
Brain Functions ◽  
The Brain ◽  
Brain Iron Deposition

The presence of iron is an important factor for normal brain functions, whereas excessive deposition of iron may impair normal cognitive function in the brain and lead to Alzheimer’s disease (AD). MRI has been widely applied to characterize brain structural and functional changes caused by AD. However, the effectiveness of using susceptibility-weighted imaging (SWI) for the analysis of brain iron deposition is still unclear, especially within the context of early AD diagnosis. Thus, in this study, we aim to explore the relationship between brain iron deposition measured by SWI with the progression of AD using various feature selection and classification methods. The proposed model was evaluated on a 69-subject SWI imaging dataset consisting of 24 AD patients, 21 mild cognitive impairment patients, and 24 normal controls. The identified AD progression-related regions were then compared with the regions reported from previous genetic association studies, and we observed considerable overlap between these two. Further, we have identified a new potential AD-related gene (MEF2C) closely related to the interaction between iron deposition and AD progression in the brain.

scholarly journals Current Paradigms to Explore the Gut Microbiota Linkage to Neurological Disorders

EMJ Neurology ◽  
2020 ◽  
pp. 68-79
Author(s):  
Varruchi Sharma ◽  
Atul Sankhyan ◽  
Anshika Varshney ◽  
Renuka Choudhary ◽  
Anil K. Sharma
Keyword(s):  
Gut Microbiota ◽  
Neurological Disorders ◽  
Brain Function ◽  
Intervention Strategy ◽  
Neurological Complications ◽  
Communication Link ◽  
Brain Functions ◽  
Current Review ◽  
The Impact ◽  
The Brain

It has been suggested that an intricate communication link exists between the gut microbiota and the brain and its ability to modulate behaviour of an individual governing homeostasis. Metabolic activity of the microbiota is considered to be relatively constant in healthy individuals, despite differences in the composition of microbiota. The metabolites produced by gut microbiota and their homeostatic balance is often perturbed as a result of neurological complications. Therefore, it is of paramount importance to explore the link between gut microbiota and brain function and behaviour through neural, endocrine, and immune pathways. This current review focusses on the impact of altered gut microbiota on brain functions and how microbiome modulation by use of probiotics, prebiotics, and synbiotics might prove beneficial in the prevention and/or treatment of neurological disorders. It is important to carefully understand the complex mechanisms underlying the gut–brain axis so as to use the gut microbiota as a therapeutic intervention strategy for neurological disorders.

scholarly journals Stem Cell Therapy for Neurodegenerative Diseases: How Do Stem Cells Bypass the Blood-Brain Barrier and Home to the Brain?

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yvonne Cashinn Chia ◽  
Clarice Evey Anjum ◽  
Hui Rong Yee ◽  
Yenny Kenisi ◽  
Mike K. S. Chan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Cellular Therapy ◽  
Immune Cell ◽  
Brain Barrier ◽  
Normal Brain ◽  
Brain Functions ◽  
Blood Brain ◽  
The Brain

Blood-brain barrier (BBB) is a term describing the highly selective barrier formed by the endothelial cells (ECs) of the central nervous system (CNS) homeostasis by restricting movement across the BBB. An intact BBB is critical for normal brain functions as it maintains brain homeostasis, modulates immune cell transport, and provides protection against pathogens and other foreign substances. However, it also prevents drugs from entering the CNS to treat neurodegenerative diseases. Stem cells, on the other hand, have been reported to bypass the BBB and successfully home to their target in the brain and initiate repair, making them a promising approach in cellular therapy, especially those related to neurodegenerative disease. This review article discusses the mechanism behind the successful homing of stem cells to the brain, their potential role as a drug delivery vehicle, and their applications in neurodegenerative diseases.

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