Cytokines as emerging regulators of central nervous system synapses

Immunity, Journal Year: 2023, Volume and Issue: 56(5), P. 914 - 925

Published: May 1, 2023

Language: Английский

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Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(19), P. 11342 - 11342

Published: Sept. 26, 2022

Multiple Sclerosis (MS) is a neuroinflammatory disorder, which histopathologically characterized by multifocal inflammatory demyelinating lesions affecting both the central nervous system's white and grey matter. Especially during progressive phases of disease, immunomodulatory treatment strategies lose their effectiveness. To develop novel MS options, pre-clinical animal models are indispensable. Among various different models, cuprizone de- remyelination model frequently used. While most studies determine tissue damage repair at histological ultrastructural level, functional readouts less commonly applied. overt deficits, gait coordination abnormalities observed in patients. Motor behavior mediated complex neural network that originates cortex terminates skeletal muscles. Several methods exist to small rodents, including rotarod testing paradigm. In this review article, we provide an overview validity characteristics test cuprizone-intoxicated mice.

Language: Английский

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The Use of Stem Cells as a Potential Treatment Method for Selected Neurodegenerative Diseases: Review

Cellular and Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 43(6), P. 2643 - 2673

Published: April 7, 2023

Stem cells have been the subject of research for years due to their enormous therapeutic potential. Most neurological diseases such as multiple sclerosis (MS), amyotrophic lateral (ALS), Alzheimer's disease (AD), Parkinson's (PD), and Huntington's (HD) are incurable or very difficult treat. Therefore new therapies sought in which autologous stem used. They often patient's only hope recovery slowing down progress symptoms. The most important conclusions arise after analyzing literature on use neurodegenerative diseases. effectiveness MSC cell therapy has confirmed ALS HD therapy. slow progression show early promising signs efficacy. In HD, they reduced huntingtin (Htt) aggregation stimulation endogenous neurogenesis. MS with hematopoietic (HSCs) inducted significant recalibration pro-inflammatory immunoregulatory components immune system. iPSC allow accurate PD modeling. patient-specific therefore minimize risk rejection and, long-term observation, did not form any tumors brain. Extracellular vesicles derived from bone marrow mesenchymal stromal (BM-MSC-EVs) Human adipose-derived stromal/stem (hASCs) widely used treat AD. Due reduction Aβ42 deposits increasing survival neurons, improve memory learning abilities. Despite many animal models clinical trial studies, still needs be refined increase its human body.

Language: Английский

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The brain cytokine orchestra in multiple sclerosis: from neuroinflammation to synaptopathology

Molecular Brain, Journal Year: 2024, Volume and Issue: 17(1)

Published: Jan. 23, 2024

Abstract The central nervous system (CNS) is finely protected by the blood–brain barrier (BBB). Immune soluble factors such as cytokines (CKs) are normally produced in CNS, contributing to physiological immunosurveillance and homeostatic synaptic scaling. CKs peptide, pleiotropic molecules involved a broad range of cellular functions, with pivotal role resolving inflammation promoting tissue healing. However, pro-inflammatory can exert detrimental effect pathological conditions, spreading damage. In inflamed recruit immune cells, stimulate local production other inflammatory mediators, promote dysfunction. Our understanding neuroinflammation humans owes much study multiple sclerosis (MS), most common autoimmune demyelinating disease, which autoreactive T cells migrate from periphery CNS after encounter still unknown antigen. CNS-infiltrating produce that aggravate demyelination neurodegeneration. This review aims recapitulate state art about healthy focus on recent advances bridging adaptive neurophysiology.

Language: Английский

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Inflammatory and anti-inflammatory cytokines bidirectionally modulate amygdala circuits regulating anxiety

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Brain-wide mapping of immune receptors uncovers a neuromodulatory role of IL-17E and the receptor IL-17RB

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Cognitive Impairment in Multiple Sclerosis: An Update on Assessment and Management

NeuroSci, Journal Year: 2022, Volume and Issue: 3(4), P. 667 - 676

Published: Nov. 22, 2022

Cognitive impairment (CI) is a core feature of multiple sclerosis (MS) and affects up to 65% patients in every phase the disease, having deep impact on all aspects patients' lives. functions most frequently involved include information processing speed, learning memory, visuospatial abilities, executive function. The precise pathogenetic mechanisms underpinning CI MS are still largely unknown, but deemed be mainly related pathological changes lesioned normal-appearing white matter, specific neuronal grey matter structures, immunological alterations, with particular synaptic transmission plasticity. Moreover, much research needed therapeutic strategies. Small moderate efficacy has been reported for disease-modifying therapies, particularly high-efficacy drugs, symptomatic therapies (dalfampridine), while strongest benefit emerged after cognitive training. present narrative review provides concise, updated overview more recent evidence prevalence, profile, mechanisms, treatment people MS. should screened regular basis as part routine clinical assessments, brief tools now widely available (such Symbol Digit Modalities Test). main goal assessment prompt implementation preventive interventions.

Language: Английский

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The relationship between chronic immune response and neurodegenerative damage in long COVID-19

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 16, 2022

In the past two years, world has faced pandemic caused by severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2), which August of 2022 infected around 619 million people and death 6.55 individuals globally. Although SARS-CoV-2 mainly affects tract level, there are several reports, indicating that other organs such as heart, kidney, pancreas, brain can also be damaged. A characteristic observed in blood serum samples patients suffering COVID-19 disease moderate stages, is a significant increase proinflammatory cytokines interferon-α (IFN-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6) interleukin-18 (IL-18), well presence autoantibodies against interferon-λ (IFN-λ), C-C motif chemokine ligand 26 (CCL26), CXC 12 (CXCL12), family with sequence similarity 19 (chemokine (C-C motif)-like) member A4 (FAM19A4), 1 (CCL1). Interestingly, it been described chronic cytokinemia related to alterations blood-brain barrier (BBB) permeability induction neurotoxicity. Furthermore, generation processes neurogenesis, neuronal repair, chemotaxis optimal microglia function. These observations support notion who survived present neurological sequelae neuropsychiatric disorders. The goal this review explore relationship between inflammatory humoral immune markers major damage manifested post-COVID-19 patients.

Language: Английский

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Upregulation of Ca2+-binding proteins contributes to VTA dopamine neuron survival in the early phases of Alzheimer’s disease in Tg2576 mice

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: Nov. 25, 2022

Recent clinical and experimental studies have highlighted the involvement of Ventral Tegmental Area (VTA) dopamine (DA) neurons for early pathogenesis Alzheimer's Disease (AD). We previously described a progressive selective degeneration these in Tg2576 mouse model AD, long before amyloid-beta plaque formation. The degenerative process DA is associated with an autophagy flux impairment, whose rescue can prevent neuronal loss. Impairments be basis accumulation damaged mitochondria, leading to disturbance calcium (Ca2+) homeostasis, functional structural deterioration neurons.In mice, we performed amperometric recordings levels analysis dopaminergic fibers Nucleus Accumbens - major component ventral striatum precociously affected AD patients together retrograde tracing, identify most vulnerable neuron subpopulations VTA. Then, focused on analyze mitochondrial integrity Apoptosis-inducing factor (AIF) localization by electron confocal microscopy, respectively. Stereological cell count was also used evaluate containing Ca2+-binding proteins Calbindin-D28K Calretinin. expression were analyzed western blot microscopy. Lastly, using electrophysiology microfluorometry VTA intrinsic properties cytosolic free Ca2+ levels.We found mesolimbic projecting striatum, located paranigral nucleus parabrachial pigmented subnucleus At onset (3 months age), accumulate while AIF translocates from mitochondria nucleus. Although describe age-dependent loss expressing or Calretinin, observed that remaining cells upregulate proteins, are significantly decreased. Coherently, TUNEL-stained express lower when compared non-apoptotic cells.Overall, our results suggest overexpression might attempt survive increasing their ability buffer Ca2+. Exploring strategies overexpress could fundamental reduce suffering improve cognitive non-cognitive functions AD.

Language: Английский

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Chronic experimental autoimmune encephalomyelitis is an excellent model to study neuroaxonal degeneration in multiple sclerosis

Frontiers in Molecular Neuroscience, Journal Year: 2022, Volume and Issue: 15

Published: Oct. 19, 2022

Animal models of multiple sclerosis (MS), specifically experimental autoimmune encephalomyelitis (EAE), have been used extensively to develop anti-inflammatory treatments. However, the similarity between MS and one particular EAE model does not end at inflammation. chronic induced in C57BL/6 mice using myelin oligodendrocyte glycoprotein (MOG) peptide 35–55 share many neuropathologies. Beyond both having white matter lesions spinal cord, also widespread neuropathology cerebral cortex, hippocampus, thalamus, striatum, cerebellum, retina/optic nerve. In this review, we compare neuropathologies each these structures with mice, find evidence that is well suited study neuroaxonal degeneration MS.

Language: Английский

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