Trends in Neurosciences
New roles for astrocytes (stars at last)
Abstract
Astrocytes have been presumed to be uninteresting for the better part of a century. Recent findings suggest unexpected new functions for these cells and highlight the importance of viewing most brain activities as a collaboration between astrocytes and neurons. Astrocytes have been implicated in dynamic regulation of neuron production, synaptic network formation, neuron electrical activity and specific neurological diseases. We are only at the threshold of understanding fully the nature and consequences of these new astrocyte functions, and there is still much to be learned about the older and better-known roles. But now, at last, astrocytes have our attention.
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Cited by (267)
Astrocytes in the spinal cord contributed to acute stress-induced gastric damage via the gap junction protein CX43
2023, Brain ResearchRat restraint water-immersion stress (RWIS) is a compound stress of high intensity and is widely used to study the pathological mechanisms of stress gastric ulcers. The spinal cord, as a part of the central nervous system, plays a dominant role in the gastrointestinal tract, but whether the spinal cord is involved in rat restraint water-immersion stress (RWIS)-induced gastric mucosal damage has not been reported. In this study, we examined the expression of spinal astrocytic glial fibrillary acidic protein (GFAP), neuronal c-Fos, connexin 43 (Cx43), and p-ERK1/2 during RWIS by immunohistochemistry and Western blotting. In addition, we intrathecally injected the astrocytic toxin L-a-aminoadipate (L-AA), gap junction blocker carbenoxolone (CBX), and ERK1/2 signaling pathway inhibitor PD98059 to explore the role of astrocytes in the spinal cord in RWIS-induced gastric mucosal damage and its possible mechanism in rats. The results showed that the expression of GFAP, c-Fos, Cx43, and p-ERK1/2 was significantly elevated in the spinal cord after RWIS. Intrathecal injection of both the astrocyte toxin L-AA and the gap junction blocker CBX significantly attenuated RWIS-induced gastric mucosal damage and decreased the activation of astrocytes and neurons induced in the spinal cord. Meanwhile, the ERK1/2 signaling pathway inhibitor PD98059 significantly inhibited gastric mucosal damage, gastric motility and RWIS-induced activation of spinal cord neurons and astrocytes. These results suggest that spinal astrocytes may regulate the RWIS-induced activation of neurons via CX43 gap junctions and play a critical role in RWIS-induced gastric mucosa damage through the ERK1/2 signaling pathway.
The link between neurology and behavior in veterinary medicine: A review
2021, Journal of Veterinary BehaviorIn veterinary behavioral medicine and in veterinary neurology, there is an effort to collaborate with different consultants, as seen both in human psychiatry and in human neurology. This cooperation can lead to a complete assessment of any case, to a more holistic collection of information regarding the development of the case, and to a synergetic vision regarding the therapy. In other words, it is essential to understand how behavioral medicine and neurology are linked together to improve diagnosis and therapy process. This review emphasizes the bond between neurology and behavior starting with the neuroanatomic basis of anomalies in veterinary behavioral medicine such as: limbic system, temporal and frontal lobe, pituitary gland, spinal cord, meninges and peripheral nerves. After that, the review deals with some disorders which overlap between neurology and behavioral medicine, and it will conclude by analyzing the differential diagnoses of the neurological diseases and their relationship with behavioral signs.
Neuroprotective Potential of Ellagic Acid: A Critical Review
2021, Advances in NutritionEllagic acid (EA) is a dietary polyphenol present in various fruits, vegetables, herbs, and nuts. It exists either independently or as part of complex structures, such as ellagitannins, which release EA and several other metabolites including urolithins following absorption. During the past few decades, EA has drawn considerable attention because of its vast range of biological activities as well as its numerous molecular targets. Several studies have reported that the oxidative stress–lowering potential of EA accounts for its broad-spectrum pharmacological attributes. At the biochemical level, several mechanisms have also been associated with its therapeutic action, including its efficacy in normalizing lipid metabolism and lipidemic profile, regulating proinflammatory mediators, such as IL-6, IL-1β, and TNF-α, upregulating nuclear factor erythroid 2-related factor 2 and inhibiting NF-κB action. EA exerts appreciable neuroprotective activity by its free radical–scavenging action, iron chelation, initiation of several cell signaling pathways, and alleviation of mitochondrial dysfunction. Numerous in vivo studies have also explored the neuroprotective attribute of EA against various neurotoxins in animal models. Despite the increasing number of publications with experimental evidence, a critical analysis of available literature to understand the full neuroprotective potential of EA has not been performed. The present review provides up-to-date, comprehensive, and critical information regarding the natural sources of EA, its bioavailability, metabolism, neuroprotective activities, and underlying mechanisms of action in order to encourage further studies to define the clinical usefulness of EA for the management of neurological disorders.
Amyloid-β<inf>1-40</inf> differentially stimulates proliferation, activation of oxidative stress and inflammatory responses in male and female hippocampal astrocyte cultures
2021, Mechanisms of Ageing and DevelopmentAlzheimer’s disease (AD) is the most common form of dementia and has a higher incidence in women. The main component of the senile plaques characteristic of AD is amyloid-beta (Aβ), with surrounding astrocytes contributing to the degenerative process. We hypothesized that the sex difference in the incidence of AD could be partially due to differential astrocytic responses to Aβ. Thus, the effect of Aβ1-40 on cell viability, the inflammatory response, and oxidative status was studied in cultures of hippocampal astrocytes from male and female rats. Aβ1-40 increased astrocyte viability in both female and male cultures by activating proliferation and survival pathways. Pro-inflammatory and anti-inflammatory responses were induced in astrocytes from both sexes. Aβ1-40 did not affect endoplasmic reticulum stress although it induced oxidative stress in male and female astrocytes. Interestingly, male astrocytes had an increase in cell number and significantly lower cell death in response to Aβ1-40. Conversely, astrocytes from females displayed a greater inflammatory response after the Aβ1-40 challenge. These results suggest that the inflammatory and oxidative environment induced by Aβ1-40 in female astrocytes may contribute to enhance the vulnerability to AD and warrants further studies to unveil the mechanisms underlying sex differences in astrocytic responses.
Role of glia in optic nerve
2021, Progress in Retinal and Eye ResearchGlial cells are critically important for maintenance of neuronal activity in the central nervous system (CNS), including the optic nerve (ON). However, the ON has several unique characteristics, such as an extremely high myelination level of retinal ganglion cell (RGC) axons throughout the length of the nerve (with virtually all fibers myelinated by 7 months of age in humans), lack of synapses and very narrow geometry. Moreover, the optic nerve head (ONH) – a region where the RGC axons exit the eye – represents an interesting area that is morphologically distinct in different species. In many cases of multiple sclerosis (demyelinating disease of the CNS) vision problems are the first manifestation of the disease, suggesting that RGCs and/or glia in the ON are more sensitive to pathological conditions than cells in other parts of the CNS. Here, we summarize current knowledge on glial organization and function in the ON, focusing on glial support of RGCs. We cover both well-established concepts on the important role of glial cells in ON health and new findings, including novel insights into mechanisms of remyelination, microglia/NG2 cell-cell interaction, astrocyte reactivity and the regulation of reactive astrogliosis by mitochondrial fragmentation in microglia.
White Matter Pathophysiology
2021, Stroke: Pathophysiology, Diagnosis, and ManagementStroke is one of the most life-threatening diseases in most countries and is a leading cause of disability in the United States. Most ischemic strokes involve both white matter and gray matter, and 20% of strokes occur predominantly in white matter. The anatomy and physiology of white matter are different compared to gray matter, and the mechanisms of white matter stroke are less understood. Axons with their myelin and myelinating oligodendrocytes are the cell types that are most vulnerable to ischemic injury. In this chapter, we summarize and describe cellular and molecular mechanisms of axon-oligodendrocyte interactions and damage after ischemic stress. Then, we discuss potential therapeutic approaches to protect white matter and to promote white-matter repair after stroke in young and aging white matter. Understanding the different pathophysiologies of white matter and gray matter after stroke will guide us in developing meaningful comprehensive stroke therapies.