scholarly journals Fractalkine Attenuates Microglial Cell Activation Induced by Prenatal Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Joanna Ślusarczyk ◽  
Ewa Trojan ◽  
Katarzyna Głombik ◽  
Katarzyna Chamera ◽  
Adam Roman ◽  
...  
Keyword(s):  
Prenatal Stress ◽  
Cell Activation ◽  
Inflammatory Factors ◽  
Potential Contribution ◽  
Fractalkine Receptor ◽  
Neuropsychiatric Diseases ◽  
Prenatally Stressed ◽  
The Brain ◽  
Receptor Cx3cr1

The potential contribution of inflammation to the development of neuropsychiatric diseases has recently received substantial attention. In the brain, the main immune cells are the microglia. As they are the main source of inflammatory factors, it is plausible that the regulation of their activation may be a potential therapeutic target. Fractalkine (CX3CL1) and its receptor CX3CR1 play a crucial role in the control of the biological activity of the microglia. In the present study, using microglial cultures we investigated whether fractalkine is able to reverse changes in microglia caused by a prenatal stress procedure. Our study found that the microglia do not express fractalkine. Prenatal stress decreases the expression of the fractalkine receptor, which in turn is enhanced by the administration of exogenous fractalkine. Moreover, treatment with fractalkine diminishes the prenatal stress-induced overproduction of proinflammatory factors such as IL-1β, IL-18, IL-6, TNF-α, CCL2, or NO in the microglial cells derived from prenatally stressed newborns. In conclusion, the present results revealed that the pathological activation of microglia in prenatally stressed newborns may be attenuated by fractalkine administration. Therefore, understanding of the role of the CX3CL1-CX3CR1 system may help to elucidate the mechanisms underlying the neuron-microglia interaction and its role in pathological conditions in the brain.

Abstract WMP31: Dedifferentiation of Smooth Muscle Cells and its Potential Contribution to Pathogenesis of Intracranial Aneurysms

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Mieko Oka ◽  
Nobuhiko Ohno ◽  
Takakazu Kawamata ◽  
Tomohiro Aoki
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Inflammatory Responses ◽  
Muscle Cells ◽  
Inflammatory Factors ◽  
Potential Contribution ◽  
Electron Microscopic

Introduction: Intracranial aneurysm (IA) affects 1 to 5 % in general public and becomes the primary cause of subarachnoid hemorrhage, the most severe form of stroke. However, currently, no drug therapy is available for IAs to prevent progression and rupture of lesions. Elucidation of mechanisms underlying the disease is thus mandatory. Considering the important role of vascular smooth muscle cells (SMCs) in the maintenance of stiffness of arterial walls and also in the pathogenesis of atherosclerosis via mediating inflammatory responses, we in the present study analyzed morphological or phenotypical changes of SMCs during the disease development in the lesions. Methods: We subjected rats to an IA model in which lesions are induced by increase of hemodynamic force loading on intracranial arterial bifurcations and performed histopathological analyses of induced lesions including the electron microscopic examination. We then immunostained specimens from induced lesions to explore factors responsible for dedifferentiation or migration of SMCs. In vitro study was also done to examine effect of some candidate factors on dedifferentiation or migration of cultured SMCs. Results: We first found the accumulation of SMCs underneath the endothelial cell layer mainly at the neck portion of the lesion. These cells was positive for the embryonic form of myosin heavy chain, a marker for the dedifferentiated SMCs, and the expression of pro-inflammatory factors like TNF-α. In immunostaining to explore the potential factor regulating the dedifferentiation of SMCs, we found that Platelet-derived growth factor-BB (PDGF-BB) was expressed in endothelial cells at the neck portion of IA walls. Consistently, recombinant PDGF-BB could promote the dedifferentiate of SMCs and chemo-attracted them in in vitro. Finally, in the stenosis model of the carotid artery, PDGF-BB expression was induced in endothelial cells in which high wall shear stress was loaded and the dedifferentiation of SMCs occurred there. Conclusions: The findings from the present study imply the role of dedifferentiated SMCs partially recruited by PDGF-BB from endothelial cells in the formation of inflammatory microenvironment at the neck portion of IA walls, leading to the progression of the disease.

Neuroinflammation in Huntington’s disease: A starring role for astrocyte and microglia

2021 ◽  
Vol 19 ◽  
Author(s):  
Julieta Saba ◽  
Federico López Couselo ◽  
Julieta Bruno ◽  
Lila Carniglia ◽  
Daniela Durand ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Genetic Disorder ◽  
Cag Repeat ◽  
Inflammatory Factors ◽  
Therapeutic Approaches ◽  
Reactive Microglia ◽  
New Treatments ◽  
The Brain

: Huntington’s disease (HD) is a neurodegenerative genetic disorder caused by a CAG repeat expansion in the huntingtin gene. HD causes motor, cognitive, and behavioral dysfunction. Since no existing treatment affects the course of this disease, new treatments are needed. Inflammation is frequently observed in HD patients before symptom onset. Neuroinflammation, characterized by the presence of reactive microglia and astrocytes and inflammatory factors within the brain, is also detected early. However, in comparison with other neurodegenerative diseases, the role of neuroinflammation in HD is much less known. Work has been dedicated to altered microglial and astrocytic functions in the context of HD, but less attention has been given to glial participation in neuroinflammation. This review describes evidence of inflammation in HD patients and animal models. It also discusses recent knowledge on neuroinflammation in HD, highlighting astrocyte and microglia involvement in the disease and considering anti-inflammatory therapeutic approaches.

scholarly journals Dynamic N6-methyladenosine RNA methylation in brain and diseases

Epigenomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 371-380 ◽  
Author(s):  
Andrew M Shafik ◽  
Emily G Allen ◽  
Peng Jin
Keyword(s):  
Brain Development ◽  
Rna Modification ◽  
Normal Brain ◽  
Biological Processes ◽  
Future Directions ◽  
Body Of Knowledge ◽  
Neuropsychiatric Diseases ◽  
The Brain ◽  
Normal Brain Development

N6-methyladenosine (m6A) is a dynamic RNA modification that regulates various aspects of RNA metabolism and has been implicated in many biological processes and transitions. m6A is highly abundant in the brain; however, only recently has the role of m6A in brain development been a focus. The machinery that controls m6A is critically important for proper neurodevelopment, and the precise mechanisms by which m6A regulates these processes are starting to emerge. However, the role of m6A in neurodegenerative and neuropsychiatric diseases still requires much elucidation. This review discusses and summarizes the current body of knowledge surrounding the function of the m6A modification in regulating normal brain development, neurodegenerative diseases and outlines possible future directions.

scholarly journals PUFA and their derivatives in neurotransmission and synapses: a new hallmark of synaptopathies

2020 ◽  
Vol 79 (4) ◽  
pp. 388-403
Author(s):  
Mathieu Di Miceli ◽  
Clémentine Bosch-Bouju ◽  
Sophie Layé
Keyword(s):  
Synapse Formation ◽  
Synaptic Function ◽  
Past Century ◽  
High Concentration ◽  
Dietary Pufa ◽  
Synaptic Functions ◽  
Neuropsychiatric Diseases ◽  
Optimal Function ◽  
The Brain

PUFA of the n-3 and n-6 families are present in high concentration in the brain where they are major components of cell membranes. The main forms found in the brain are DHA (22 :6, n-3) and arachidonic acid (20:4, n-6). In the past century, several studies pinpointed that modifications of n-3 and n-6 PUFA levels in the brain through dietary supply or genetic means are linked to the alterations of synaptic function. Yet, synaptopathies emerge as a common characteristic of neurodevelopmental disorders, neuropsychiatric diseases and some neurodegenerative diseases. Understanding the mechanisms of action underlying the activity of PUFA at the level of synapses is thus of high interest. In this frame, dietary supplementation in PUFA aiming at restoring or promoting the optimal function of synapses appears as a promising strategy to treat synaptopathies. This paper reviews the link between dietary PUFA, synapse formation and the role of PUFA and their metabolites in synaptic functions.

scholarly journals The Role of Endothelial Microparticle in Coronary Heart Disease as The Complications of Diabetes Mellitus

2019 ◽  
Vol 4 (1) ◽  
pp. 31-39
Author(s):  
Eka Fithra Elfi ◽  
Yose Ramda Ilhami ◽  
Eryati Darwin
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Endothelial Dysfunction ◽  
Cell Activation ◽  
Inflammatory Factors ◽  
Endothelial Cell Activation ◽  
Complications Of Diabetes

  Coronary heart disease (CHD) is caused by obstruction of coronary blood flow due to endothelial dysfunction triggered by various genetic and non-genetic risk factors such as hyperlipidemia, hypertension, hyperglycemia and obesity. Endothelial cell activation due to hyperglycaemia in diabetes mellitus induces production of pro-inflammatory factors that damage the cell membrane triggering the formation of membrane particles called microparticles. Endothe-lial microparticles contain proteins including endothelial nitric oxide synthase (eNOS) which plays a role in the production of nitric oxide (NO). To determine the role of microparticles in the occurrence of coro-nary heart disease in diabetes mellitus due to endothelial dysfunction, a study was conducted by comparing the levels of eNOS and NO in DM patients who had CHD with DM patients who had no CHD. Blood samples from 20 DM patients who had CHD and 20 DM patients who had no CHD of the outpatients in Cardiology Department and Inter-nal Medicine department of regional public hospital were included in this study. All patients were fulfilled inclusion and exclusion criteria and diagnosed by the appropriate specialist. The eNOS and NO lev-els were measured using the ELISA method. The results of this study show that eNOS levels in the group of DM patients who had CHD (21,292±12,415 ng/ml) were significantly lower (p <0.05) than those in the group of DM patients who had no CHD (29,721±11,952 ng/ml). Nitric oxide levels in DM patients who had CHD (0,053±0,021 nmol/ μl) were not statistically different to the levels in DM patients who had no CHD (0,047±0,032 nmol/μl). From the results of this study we concluded that endothelial microparticle protein eNOS plays a role in the occurrence of CHD due to the complications of diabetes mellitus 

scholarly journals Changes in expression of GFAP, ApoE and APP mRNA and protein levels in the adult rat brain following cortical injury

2013 ◽  
Vol 65 (1) ◽  
pp. 255-264
Author(s):  
Natasa Loncarevic-Vasiljkovic ◽  
Vesna Pesic ◽  
N. Tanic ◽  
Desanka Milanovic ◽  
Aleksandra Mladenovic-Djordjevic ◽  
...  
Keyword(s):  
Brain Plasticity ◽  
Recovery Period ◽  
Potential Contribution ◽  
Cortical Injury ◽  
Adult Rat ◽  
Protein Levels ◽  
Adult Rat Brain ◽  
Apoe Protein ◽  
The Brain

The recovery period following cortical injury (CI) is characterized by a dynamic and highly complex interplay between beneficial and detrimental events. The aim of this study was to examine the expressions of Glial Fibrillary Acidic Protein (GFAP), Apolipoprotein E (ApoE) and Amyloid Precursor Protein (APP), all of which are involved in brain plasticity and neurodegeneration. Our results reveal that CI strongly influenced GFAP, ApoE and APP mRNA expression, as well as GFAP and ApoE protein expression. Considering the pivotal role of these proteins in the brain, the obtained results point to their potential contribution in neurodegeneration and consequent Alzheimer?s disease development.

scholarly journals Early and long-term neuroendocrine effects of prenatal stress in male and female rats

2000 ◽  
Vol 46 (1) ◽  
pp. 30-34 ◽  
Author(s):  
A. G. Reznikov ◽  
N. D. Nosenko ◽  
L. V. Tarasenko ◽  
P. V. Sinitsyn ◽  
L. I. Polyakova
Keyword(s):  
Prenatal Stress ◽  
Stress Reactivity ◽  
Female Rats ◽  
Male And Female Rats ◽  
Prenatally Stressed ◽  
Old Rats ◽  
Males And Females ◽  
Morphological Equivalent ◽  
The Brain

The effect of maternal stress or so-called prenatal stress (PS) on the neuroendocrine regulation of reproduction and stress reactivity of the progeny was studied. Prenatal stress prevented the formation of sex dimorphism of catecholamine content and aromatase and androgen 5a-reductase activities in the preoptic region of the brain and mediobasal hypothalamus of 10-day-old rats. Leveling of sex-specific differences in the size of the neurocyte nuclei in the suprachiasmatic nucleus was the morphological equivalent of functional disorders induced by PS. Stress and adrenergic reactivity of the hypothalamo-pituitary-adrenal system was changed in prenatally stressed males and females. Remote effects of PS are regarded as a manifestation of disorders in the hormone neurotransmitter imprinting of the neuroendocrine system.

scholarly journals A controversial role of neutrophils in tuberculosis infection pathogenesis

2021 ◽  
Vol 11 (5) ◽  
pp. 809-819
Author(s):  
I. A. Linge ◽  
A. S. Apt
Keyword(s):  
T Cell Activation ◽  
Lung Tissue ◽  
Cell Activation ◽  
Medical Problem ◽  
Protective Role ◽  
Inflammatory Factors ◽  
Tissue Destruction ◽  
Infectious Process ◽  
Dendritic Cell Migration

Tuberculosis (TB) continues to be an important and unresolved medical problem. About a quarter of mankind is infected with Mycobacterium tuberculosis, and about 5–10% of these people eventually develop TB. Macrophages and CD4+ T cells are considered the key cells providing defense against TB infection. The role of neutrophils in TB is less well defined. Neutrophils are short-lived granulocytes among first migrate into the infectious lung tissue and phagocy tose mycobacteria. On the one hand, there is evidence for protective role of neutrophils in TB released via anti-microbial peptides inhibiting mycobacterial growth, up-regulation of CD4+ T-cell activation, and dendritic cell migration in the lymph nodes. On the other hand, infection of genetically TB susceptible animals leads to an overwhelming lung neutrophil inflammation, development of necrotic granulomata, and a rapid death. Neutrophils act directly or indirectly on mycobacteria by different oxidative or other reactions including neutrophil extracellular traps (NETs) formation. Phagocytosis of mycobacteria by neutrophils is accompanied by the production of pro-inflammatory factors, thus making neutrophils active participants of inflammation in all stages of the infectious process. Finally, neutrophils die by apoptosis or necrosis. Necrosis of neutrophils, which is activated by reactive oxygen species, also prolongs the inflammation. In this way, there is strong evidence that neutrophils are the cells involved in the transition of infection to the terminal stage, participating in lung tissue destruction. Although neutrophils evolutionary developed many ways to resist pathogens, it is likely, that neutrophils do not possess sufficient anti-mycobactericidal capacities due to the development of many adaptations allowing mycobacteria to survive inside the neutrophils. Neutrophils effectively phagocytose but poorly kill mycobacteria, thus hiding bacilli from more efficient killers, macrophages, and playing the role of the “Trojan Horse”. In this review, we summarize the data on the involvement of neutrophils in TB inflammation. We discuss their ambiguous role in pathogenesis which depends upon mycobacterial virulence, host genetics, dynamics of migration to inflammatory foci, and persistence during initial and chronic stages of the infectious process.

Sign in / Sign up

Export Citation Format

Share Document