Altered astrocytic function in experimental neuroinflammation and multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that affects about 2.5 million people worldwide. In MS, the patients’ immune system starts to attack the myelin sheath, leading to demyelination, neurodegeneration, and, ultimately, loss of vital neurological functions such as walking. There is currently no cure for MS and the available treatments only slow the initial phases of the disease. The later‐disease mechanisms are poorly understood and do not directly correlate with the activity of immune system cells, the main target of the available treatments. Instead, evidence suggests that disease progression and disability are better correlated with the maintenance of a persistent low‐grade inflammation inside the CNS, driven by local glial cells, like astrocytes and microglia. Depending on the context, astrocytes can (a) exacerbate inflammation or (b) promote immunosuppression and tissue repair. In this review, we will address the present knowledge that exists regarding the role of astrocytes in MS and experimental animal models of the disease.

Discovery of Novel Biomarkers for Diagnosing and Predicting the Progression of Multiple Sclerosis Using TMT-Based Quantitative Proteomics

“…It is the main cause of severe neurological effects and disabilities in young adults ( 1 ). An estimated 2.5 million people worldwide are affected with MS, and it is more common in women than in men ( 2 ). In MS, symptoms exhibit a substantial degree of heterogeneity.…”

Reactive Astrocytes Contribute to Alzheimer’s Disease-Related Neurotoxicity and Synaptotoxicity in a Neuron-Astrocyte Co-culture Assay

“…Particularly, 2x N/1x A co-cultures showing 1092.3800 ± 296.4193 sum of intersections and 1x N/1x A 938.167 ± 236.8746 and 2x N/2x A co-cultures showing 1342.22 ± 238.6329 sum of intersections (Figure 4). Key metrics were analyzed as they derive from a polynomial function that can be plotted after running the Sholl analysis plugin, and using a built-in heuristic algorithm in the Sholl analysis plugin, approximating the polynomial function from a linear Sholl plot and, thus, improving local variations of sampled data (das Neves et al, 2021). Interestingly, results of the key metrics were similar to the results above.…”

“…Although we studied the role of AD-related stimulators in our project, our model could well be used to study the impact of astrocytes in the context of other neurodegenerative or neuroinflammatory diseases. These include Tauopathies, Parkinson's disease, Amyotrophic Lateral sclerosis, and multiple sclerosis (das Neves et al, 2021). Here, different isoforms of phosphorylated, aggregated Tau or myelin debris could be used to pre-stimulate astrocytes and investigate their dysregulation and the subsequent effect on neuronal survival.…”

Clemastine Ameliorates Perioperative Neurocognitive Disorder in Aged Mice Caused by Anesthesia and Surgery

“…Neuroinflammation is one of the main causes of demyelination. Multiple sclerosis, a chronic inflammatory disease of the central nervous system, characterized by demyelination, can lead to neurodegeneration and neurological function’s impairment ( das Neves et al, 2020 ). Besides, demyelination has been found in the frontal cortex in Alzheimer’s disease patients ( Ferrer and Andrés-Benito, 2020 ), which leaded to cognitive impairment in population at high risk for dementia in Alzheimer’s disease ( Kövari et al, 2007 ; Vanzulli et al, 2020 ).…”

“…Meanwhile, neuroinflammation induces axonal hypomyelination through the overactivation of WNT/β-catenin signal pathway ( Huang et al, 2020 ). In other words, neuroinflammation is one of the main factors leading to demyelination ( Huang et al, 2020 ; das Neves et al, 2020 ; Borgonetti et al, 2020 ). Demyelination pathological changes widely exist in many kinds of neurodegenerative, brain injury and cognitive impairment diseases, such as Alzheimer’s disease, multiple sclerosis, stroke, traumatic brain injury and spinal cord injury ( Mayne et al, 2020 ).…”