The Latest Articles on Astrocytes in Neurodegenerative Diseases
Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles on astrocytes in neurodegenerative diseases.
Title: Astrocytes in selective vulnerability to neurodegenerative disease
Authors: Till S. Zimmer, Adam L. Orr, Anna G. Orr
Type: Review
Abstract:
Selective vulnerability of specific brain regions and cell populations is a hallmark of neurodegenerative disorders. Mechanisms of selective vulnerability involve neuronal heterogeneity, functional specializations, and differential sensitivities to stressors and pathogenic factors. In this review we discuss the growing body of literature suggesting that, like neurons, astrocytes are heterogeneous and specialized, respond to and integrate diverse inputs, and induce selective effects on brain function. In disease, astrocytes undergo specific, context-dependent changes that promote different pathogenic trajectories and functional outcomes. We propose that astrocytes contribute to selective vulnerability through maladaptive transitions to context-divergent phenotypes that impair specific brain regions and functions. Further studies on the multifaceted roles of astrocytes in disease may provide new therapeutic approaches to enhance resilience against neurodegenerative disorders.
Access this article: https://doi.org/10.1016/j.tins.2024.02.008
Title: Morphological changes in perisynaptic astrocytes induced by dopamine neuronal degeneration in the striatum of rats
Authors: Liping Sun, Xuefeng Zheng, Yichen Che, Ye Zhang, Ziyun Huang, Linju Jia, Yaofeng Zhu, Wanlong Lei, Guoqing Guo, Chunkui Shao
Type: Research Article
Abstract:
Introduction
The typical functionality of astrocytes was previously shown to be disrupted by Parkinson's disease (PD), which actively regulates synaptic neurotransmission. However, the morphological changes in astrocytes wrapping glutamatergic synapses in the striatum after dopamine (DA) neuronal degeneration is unclear.
Methods
We utilized a range of methodologies, encompassing the 6-hydroxydopamine (6OHDA)-induced PD model, as well as techniques such as immunohistochemistry, Western blotting, immunofluorescence and immunoelectron microscopy (IEM) to delve into the consequences of DA neuronal degeneration on the morphological attributes of perisynaptic astrocytes.
Results
Our findings demonstrated a notable rise in glial fibrillary acidic protein (GFAP) + astrocyte density and an upregulation in GFAP protein expression within the striatum due to DA neuronal degeneration, coincided with the enlargement, elongation, and thickening of astrocyte protuberances. However, the expression levels of glutamate transporter 1 (GLT1) and glutamine synthetase (GS), which are related to glutamate–glutamine cycle, were significantly reduced. Double immunofluorescence and IEM results indicated that different proportions of vesicular glutamate transporter 1 (VGlut1)+ and vesicular glutamate transporter 2 (VGlut2) + terminals were wrapped by astrocytes. Additionally, DA neuronal degeneration increased the percentage and area of VGlut1+ and VGlut2+ terminals wrapped by GFAP + astrocytes in the striatum. Furthermore, we noted that DA neuronal degeneration increased the percentage of VGlut1+ and VGlut2+ axo-spinous synapses wrapped by astrocytes but had no effect on axo-dendritic synapses.
Conclusion
Hence, perisynaptic astrocytes wrapping striatal glutamatergic synapses exhibit substantial morphological and functional alterations following DA neuronal degeneration making them a potential target for therapeutic interventions in PD.
Access this article: https://doi.org/10.1016/j.heliyon.2024.e27637
Title: Tunneling nanotubes: The transport highway for astrocyte-neuron communication in the central nervous system
Authors: Cuixiang Zhou, Min Huang, Shasha Wang, Shifeng Chu, Zhao Zhang, Naihong Chen
Type: Review
Abstract
Tunneling nanotubes (TNTs) have emerged as pivotal structures for intercellular communication, enabling the transfer of cellular components across distant cells. Their involvement in neurological disorders has attracted considerable scientific interest. This review delineates the functions of TNTs within the central nervous system, examining their role in the transmission of bioenergetic substrates, and signaling molecules, and their multifaceted impact on both physiological and pathological processes, with an emphasis on neurodegenerative diseases. The review highlights the selectivity and specificity of TNTs as dedicated pathways for intercellular cargo delivery, particularly under stress conditions that provoke increased TNT formation. The potential of TNTs as therapeutic targets is explored in depth. We pay particular attention to the interactions between astrocytes and neurons mediated by TNTs, which are fundamental to brain architecture and function. Dysfunctions in these interactions are implicated in the spread of protein aggregates and mitochondrial anomalies, contributing to the pathogenesis of neurodegenerative diseases. The review culminates with a synthesis of the current understanding of TNT biology and identifies research gaps, advocating for intensified exploration into TNTs as a promising therapeutic frontier.
Access this article: https://doi.org/10.1016/j.brainresbull.2024.110921
Title: Cytokine profiling in senescent and reactive astrocytes: A systematic review
Authors: Michel López-Teros, Adriana Alarcón-Aguilar, Alejandra Castillo-Aragón, Mina Königsberg, Armando Luna-López
Type: Review
Abstract:
Astrocytes play an important role in neuroinflammation by producing proinflammatory molecules. In response to various stressful stimuli, astrocytes can become senescent or reactive, both are present in age-associated cognitive impairment and other neurodegenerative diseases, and contribute to neuroinflammation. However, there are no studies that compare the cytokines secreted by these types of astrocytes in the brain during aging. Hence, we aimed to broaden the picture of the secretory profiles and to differentiate the variability between them. Therefore, a systematic review was conducted following the guidelines of the “Reporting Items for Systematic Review and Meta-Analyses”. Only three studies that met the inclusion terms evaluated age-related cytokine secretion, however, no evaluation of senescence or gliosis was performed. Consequently, to increase the spectrum of the review, studies where those phenotypes were induced and cytokines determined were included. Although some cytokines were common for gliosis and senescence, some interesting differences were also found. The dissimilarities in cytokines secretion between these phenotypes could be studied in the future as potential markers.
Access this article: https://doi.org/10.1016/j.neurobiolaging.2024.02.012
Title: Histamine and receptors in neuroinflammation: Their roles on neurodegenerative diseases
Authors: Zhenyu Zhou, Qi An, Wanying Zhang, Yixin Li, Qihang Zhang, Haijing Yan
Type: Review
Abstract:
Histamine, an auto-reactive substance and mediator of inflammation, is synthesized from histidine through the action of histidine decarboxylase (HDC). It primarily acts on histamine receptors in the central nervous system (CNS). Increasing evidence suggests that histamine and its receptors play a crucial role in neuroinflammation, thereby modulating the pathology of neurodegenerative diseases. Recent studies have demonstrated that histamine regulates the phenotypic switching of microglia and astrocytes, inhibits the production of pro-inflammatory cytokines, and alleviates inflammatory responses. In the CNS, our research group has also found that histamine and its receptors are involved in regulating inflammatory responses and play a central role in ameliorating chronic neuroinflammation in neurodegenerative diseases. In this review, we will discuss the role of histamine and its receptors in neuroinflammation associated with neurodegenerative diseases, potentially providing a novel therapeutic target for the treatment of chronic neuroinflammation-related neurodegenerative diseases in clinical settings.
Access this article: https://doi.org/10.1016/j.bbr.2024.114964
