scholarly journals The Role of Microglia in Cerebral Traumatic Injury and its Therapeutic Implications

2020 ◽  
Vol 17 (02) ◽  
pp. 069-073
Author(s):  
Huber S. Padilla-Zambrano ◽  
Harsh Deora ◽  
Mohamed Arnout ◽  
Romario Mendoza-Florez ◽  
Wiston Eduardo Cardenas-Chavez ◽  
...  
Keyword(s):  
Animal Studies ◽  
Traumatic Injury ◽  
Microglia Activation ◽  
Current Evidence ◽  
Therapeutic Implications ◽  
Synaptic Remodeling ◽  
Damage Repair ◽  
The Central Nervous System ◽  
Pharmacological Manipulations

AbstractMicroglia have a variety of functions in the brain such as synaptic remodeling, damage repair of the central nervous system (CNS), and CNS’ inflammatory response to peripheral infections. The response depends on the type of insult and infection and includes a range of variety of activation states, the duration of which will decide the outcome. In response to traumatic brain injury (TBI), early activation can lead to early restoration of function, while prolonged and continuous activation can cause neurodegeneration states. Current evidence, however, states that this may not be the case. In this article, we discuss this seldom understood topic of microglia response to TBI, and analyze their distribution, function and possible sites of manipulation. Animal studies have allowed genetic and pharmacological manipulations of microglia activation, in order to define their role. Microglia activation can be remote to the site of injury, and thus their manipulation may play a significant role in the response to any trauma.

scholarly journals Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 249
Author(s):  
Ana Checa-Ros ◽  
Antonio Jeréz-Calero ◽  
Antonio Molina-Carballo ◽  
Cristina Campoy ◽  
Antonio Muñoz-Hoyos
Keyword(s):  
Gut Microbiome ◽  
Pediatric Patients ◽  
Neurodevelopmental Disorder ◽  
Current Evidence ◽  
Omega 3 ◽  
Therapeutic Implications ◽  
Neuropsychiatric Diseases ◽  
Bidirectional Relationship ◽  
The Central Nervous System

Studies suggest that the bidirectional relationship existent between the gut microbiome (GM) and the central nervous system (CNS), or so-called the microbiome–gut–brain axis (MGBA), is involved in diverse neuropsychiatric diseases in children and adults. In pediatric age, most studies have focused on patients with autism. However, evidence of the role played by the MGBA in attention deficit/hyperactivity disorder (ADHD), the most common neurodevelopmental disorder in childhood, is still scanty and heterogeneous. This review aims to provide the current evidence on the functioning of the MGBA in pediatric patients with ADHD and the specific role of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in this interaction, as well as the potential of the GM as a therapeutic target for ADHD. We will explore: (1) the diverse communication pathways between the GM and the CNS; (2) changes in the GM composition in children and adolescents with ADHD and association with ADHD pathophysiology; (3) influence of the GM on the ω-3 PUFA imbalance characteristically found in ADHD; (4) interaction between the GM and circadian rhythm regulation, as sleep disorders are frequently comorbid with ADHD; (5) finally, we will evaluate the most recent studies on the use of probiotics in pediatric patients with ADHD.

scholarly journals Loss of microglial SIRPα promotes synaptic pruning in preclinical models of neurodegeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xin Ding ◽  
Jin Wang ◽  
Miaoxin Huang ◽  
Zhangpeng Chen ◽  
Jing Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Knock Out ◽  
Classical Complement Pathway ◽  
Synaptic Remodeling ◽  
The Central Nervous System ◽  
System Activation ◽  
Knock Out Mice ◽  
Synaptic Pruning

AbstractMicroglia play a key role in regulating synaptic remodeling in the central nervous system. Activation of classical complement pathway promotes microglia-mediated synaptic pruning during development and disease. CD47 protects synapses from excessive pruning during development, implicating microglial SIRPα, a CD47 receptor, in synaptic remodeling. However, the role of microglial SIRPα in synaptic pruning in disease remains unclear. Here, using conditional knock-out mice, we show that microglia-specific deletion of SIRPα results in decreased synaptic density. In human tissue, we observe that microglial SIRPα expression declines alongside the progression of Alzheimer’s disease. To investigate the role of SIRPα in neurodegeneration, we modulate the expression of microglial SIRPα in mouse models of Alzheimer’s disease. Loss of microglial SIRPα results in increased synaptic loss mediated by microglia engulfment and enhanced cognitive impairment. Together, these results suggest that microglial SIRPα regulates synaptic pruning in neurodegeneration.

scholarly journals The Role of the Innate Immune System in Alzheimer’s Disease and Frontotemporal Lobar Degeneration: An Eye on Microglia

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Elisa Ridolfi ◽  
Cinzia Barone ◽  
Elio Scarpini ◽  
Daniela Galimberti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Lobar Degeneration ◽  
Environmental Changes ◽  
Current Evidence ◽  
Neuronal Function ◽  
Immune Effector ◽  
Effector Cells ◽  
The Central Nervous System

In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS). They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.

Role of Gut Microbiota in Multiple Sclerosis and Potential Therapeutic Implications

2021 ◽  
Vol 19 ◽  
Author(s):  
Xu Wang ◽  
Zhen Liang ◽  
Shengnan Wang ◽  
Di Ma ◽  
Mingqin Zhu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gut Microbiota ◽  
Demyelinating Disease ◽  
Inflammatory Diseases ◽  
Intestinal Barrier ◽  
Autoimmune Response ◽  
Therapeutic Implications ◽  
The Central Nervous System ◽  
Underlying Mechanisms

: The role of gut microbiota in health and diseases has been receiving increased attention recently. Emerging evidence from previous studies on the gut-microbiota-brain axis highlighted the importance of gut microbiota in neurological disorders. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) resulting from T-cell-driven, myelin-directed autoimmunity. The dysbiosis of gut microbiota in MS patients has been reported in published research studies, indicating that gut microbiota plays an important role in the pathogenesis of MS. Gut microbiota has also been reported to influence the initiation of disease and severity of experimental autoimmune encephalomyelitis, which is the animal model of MS. However, the underlying mechanisms of gut microbiota involvement in the pathogenesis of MS remain unclear. Therefore, in this review, we summerized the potential mechanisms for gut microbiota involvement in the pathogenesis of MS, including increasing the permeability of the intestinal barrier, initiating an autoimmune response, disrupting the blood-brain barrier integrity, and contributing to chronic inflammation. The possibility for gut microbiota as a target for MS therapy has also been discussed. This review provides new insight into understanding the role of gut microbiota in neurological and inflammatory diseases.

scholarly journals New Evidence on the Role of D-Aspartate Metabolism in Regulating Brain and Endocrine System Physiology: From Preclinical Observations to Clinical Applications

2020 ◽  
Vol 21 (22) ◽  
pp. 8718
Author(s):  
Alessandro Usiello ◽  
Maria Maddalena Di Fiore ◽  
Arianna De Rosa ◽  
Sara Falvo ◽  
Francesco Errico ◽  
...  
Keyword(s):  
Animal Studies ◽  
Endocrine System ◽  
Postnatal Life ◽  
Functional Development ◽  
The Central Nervous System ◽  
High Concentrations ◽  
System Physiology ◽  
Metabolizing Enzyme

The endogenous amino acids serine and aspartate occur at high concentrations in free D-form in mammalian organs, including the central nervous system and endocrine glands. D-serine (D-Ser) is largely localized in the forebrain structures throughout pre and postnatal life. Pharmacologically, D-Ser plays a functional role by acting as an endogenous coagonist at N-methyl-D-aspartate receptors (NMDARs). Less is known about the role of free D-aspartate (D-Asp) in mammals. Notably, D-Asp has a specific temporal pattern of occurrence. In fact, free D-Asp is abundant during prenatal life and decreases greatly after birth in concomitance with the postnatal onset of D-Asp oxidase expression, which is the only enzyme known to control endogenous levels of this molecule. Conversely, in the endocrine system, D-Asp concentrations enhance after birth during its functional development, thereby suggesting an involvement of the amino acid in the regulation of hormone biosynthesis. The substantial binding affinity for the NMDAR glutamate site has led us to investigate the in vivo implications of D-Asp on NMDAR-mediated responses. Herein we review the physiological function of free D-Asp and of its metabolizing enzyme in regulating the functions of the brain and of the neuroendocrine system based on recent genetic and pharmacological human and animal studies.

Regulatory role of NGFs in neurocognitive functions

2017 ◽  
Vol 28 (6) ◽  
pp. 649-673 ◽  
Author(s):  
Ashutosh Kumar ◽  
Vikas Pareek ◽  
Muneeb A. Faiq ◽  
Pavan Kumar ◽  
Khursheed Raza ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Adult Brain ◽  
Current Evidence ◽  
Future Research ◽  
Neurocognitive Dysfunction ◽  
Neurocognitive Functions ◽  
The Central Nervous System ◽  
Health And Disease

AbstractNerve growth factors (NGFs), especially the prototype NGF and brain-derived neurotrophic factor (BDNF), have a diverse array of functions in the central nervous system through their peculiar set of receptors and intricate signaling. They are implicated not only in the development of the nervous system but also in regulation of neurocognitive functions like learning, memory, synaptic transmission, and plasticity. Evidence even suggests their role in continued neurogenesis and experience-dependent neural network remodeling in adult brain. They have also been associated extensively with brain disorders characterized by neurocognitive dysfunction. In the present article, we aimed to make an exhaustive review of literature to get a comprehensive view on the role of NGFs in neurocognitive functions in health and disease. Starting with historical perspective, distribution in adult brain, implied molecular mechanisms, and developmental basis, this article further provides a detailed account of NGFs’ role in specified neurocognitive functions. Furthermore, it discusses plausible NGF-based homeostatic and adaptation mechanisms operating in the pathogenesis of neurocognitive disorders and has presents a survey of such disorders. Finally, it elaborates on current evidence and future possibilities in therapeutic applications of NGFs with an emphasis on recent research updates in drug delivery mechanisms. Conclusive remarks of the article make a strong case for plausible role of NGFs in comprehensive regulation of the neurocognitive functions and pathogenesis of related disorders and advocate that future research should be directed to explore use of NGF-based mechanisms in the prevention of implicated diseases as well as to target these molecules pharmacologically.

scholarly journals Not merely a protective packing organ? A review of fascia and its force transmission capacity

2018 ◽  
Vol 124 (1) ◽  
pp. 234-244 ◽  
Author(s):  
Jan Wilke ◽  
Robert Schleip ◽  
Can A. Yucesoy ◽  
Winfried Banzer
Keyword(s):  
Animal Studies ◽  
Biomechanical Properties ◽  
Force Transmission ◽  
Locomotor System ◽  
Myofascial Force Transmission ◽  
Transmitted Force ◽  
Muscle Fascia ◽  
The Central Nervous System

Recent research indicates that fascia is capable of changing its biomechanical properties. Moreover, as it links the skeletal muscles, forming a body-wide network of multidirectional myofascial continuity, the classical conception of muscles as independent actuators has been challenged. Hence, the present synthesis review aims to characterize the mechanical relevance of the connective tissue for the locomotor system. Results of cadaveric and animal studies suggest a clinically relevant myofascial force transmission to neighboring structures within one limb (e.g., between synergists) and in the course of muscle-fascia chains (e.g., between leg and trunk). Initial in vivo trials appear to underpin these findings, demonstrating the existence of nonlocal exercise effects. However, the factors influencing the amount of transmitted force (e.g., age and physical activity) remain controversial, as well as the role of the central nervous system within the context of the observed remote exercise effects.

scholarly journals Epigenetics of Alzheimer’s Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 195
Author(s):  
Matea Nikolac Perkovic ◽  
Alja Videtic Paska ◽  
Marcela Konjevod ◽  
Katarina Kouter ◽  
Dubravka Svob Strac ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Posttranslational Modifications ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Current Evidence ◽  
Mtdna Copy Number ◽  
Rna Regulation ◽  
The Central Nervous System

There are currently no validated biomarkers which can be used to accurately diagnose Alzheimer’s disease (AD) or to distinguish it from other dementia-causing neuropathologies. Moreover, to date, only symptomatic treatments exist for this progressive neurodegenerative disorder. In the search for new, more reliable biomarkers and potential therapeutic options, epigenetic modifications have emerged as important players in the pathogenesis of AD. The aim of the article was to provide a brief overview of the current knowledge regarding the role of epigenetics (including mitoepigenetics) in AD, and the possibility of applying these advances for future AD therapy. Extensive research has suggested an important role of DNA methylation and hydroxymethylation, histone posttranslational modifications, and non-coding RNA regulation (with the emphasis on microRNAs) in the course and development of AD. Recent studies also indicated mitochondrial DNA (mtDNA) as an interesting biomarker of AD, since dysfunctions in the mitochondria and lower mtDNA copy number have been associated with AD pathophysiology. The current evidence suggests that epigenetic changes can be successfully detected, not only in the central nervous system, but also in the cerebrospinal fluid and on the periphery, contributing further to their potential as both biomarkers and therapeutic targets in AD.

scholarly journals Advances in the pathophysiology of adult-onset focal dystonias: recent neurophysiological and neuroimaging evidence

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 67 ◽  
Author(s):  
Antonella Conte ◽  
Giovanni Defazio ◽  
Marcello Mascia ◽  
Daniele Belvisi ◽  
Patrizia Pantano ◽  
...  
Keyword(s):  
Sensory Processing ◽  
Animal Studies ◽  
Focal Dystonia ◽  
Current Evidence ◽  
Adult Onset ◽  
Brain Areas ◽  
Sensory Abnormalities ◽  
Involuntary Muscle ◽  
Cerebellar Involvement

Focal dystonia is a movement disorder characterized by involuntary muscle contractions that determine abnormal postures. The traditional hypothesis that the pathophysiology of focal dystonia entails a single structural dysfunction (i.e. basal ganglia) has recently come under scrutiny. The proposed network disorder model implies that focal dystonias arise from aberrant communication between various brain areas. Based on findings from animal studies, the role of the cerebellum has attracted increased interest in the last few years. Moreover, it has been increasingly reported that focal dystonias also include nonmotor disturbances, including sensory processing abnormalities, which have begun to attract attention. Current evidence from neurophysiological and neuroimaging investigations suggests that cerebellar involvement in the network and mechanisms underlying sensory abnormalities may have a role in determining the clinical heterogeneity of focal dystonias.

scholarly journals The Emerging Role of BDNF/TrkB Signaling in Cardiovascular Diseases

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 70
Author(s):  
Peng-Zhou Hang ◽  
Hua Zhu ◽  
Pei-Feng Li ◽  
Jie Liu ◽  
Feng-Qin Ge ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Metabolic Diseases ◽  
Current Evidence ◽  
Downstream Signaling ◽  
Diagnosis And Prognosis ◽  
Potential Biomarker ◽  
The Central Nervous System ◽  
Artery Disease ◽  
Novel Therapeutic Strategies

Brain-derived neurotrophic factor (BDNF) is one of the most abundant neurotrophins in the central nervous system. Numerous studies suggest that BDNF has extensive roles by binding to its specific receptor, tropomyosin-related kinase receptor B (TrkB), and thereby triggering downstream signaling pathways. Recently, growing evidence highlights that the BDNF/TrkB pathway is expressed in the cardiovascular system and closely associated with the development and outcome of cardiovascular diseases (CVD), including coronary artery disease, heart failure, cardiomyopathy, hypertension, and metabolic diseases. Furthermore, circulating BDNF has also been revealed as a new potential biomarker for both diagnosis and prognosis of CVD. In this review, we discuss the current evidence of the emerging role of BDNF/TrkB signaling and address the challenges that remain in translating these discoveries to novel therapeutic strategies for CVD.

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