{"title":"Neuroglia and extracellular matrix molecules.","authors":"Egor Dzyubenko, Dirk M Hermann","doi":"10.1016/B978-0-443-19104-6.00010-3","DOIUrl":"10.1016/B978-0-443-19104-6.00010-3","url":null,"abstract":"<p><p>This chapter provides a comprehensive overview of the roles of astrocytes, microglia, and the extracellular matrix (ECM) in regulating neuroplasticity and maintaining brain homeostasis. Astrocytes provide essential metabolic support to neurons, regulate synapse development, support neuroplasticity mechanisms, and modulate neurotransmission. Microglia, the resident immune cells of the brain, play a critical role in neuroinflammatory responses and homeostatic brain regulation by modulating synapse formation and pruning. The extracellular space (ECS) mediates intercellular interactions, provides a highly regulated environment for intercellular communication, and is filled with ECM molecules. Proteoglycans and polysaccharides of the ECM play a vital role not only in brain development but also in brain function throughout life. In the injured brain, neuroplasticity and regeneration can be bidirectionally regulated as a result of the interplay between ECM, astrocytes, and microglia. The modulation of synaptic strength, structural remodeling, and modification of intrinsic neuronal properties are among the central mechanisms that contribute to neuronal plasticity in health and disease. We believe that the understanding of ECM-glia interactions and their role in neuroplasticity regulation is key to the development of novel therapeutic strategies in neurologic disorders.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"209 ","pages":"197-211"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Brain and behavioral asymmetries in nonprimate species.","authors":"Elisa Frasnelli, Giorgio Vallortigara","doi":"10.1016/B978-0-443-15646-5.00011-7","DOIUrl":"10.1016/B978-0-443-15646-5.00011-7","url":null,"abstract":"<p><p>Brain and behavioral asymmetries are widespread across the animal kingdom, suggesting that even simpler nervous systems benefit from such features. In the last 30 years, research conducted on several vertebrate (but also invertebrate) animal models has massively contributed to our understanding of the causation, development, evolution, and function of lateralization. Here, we review some of this research, highlighting the importance of studying this topic in nonprimate species for a deeper understanding of the mechanisms behind cerebral asymmetries. We report evidence of handedness and motor asymmetries as well as the results of research on perceptual and cognitive asymmetries in nonprimate animals, analyzing the contribution of such studies in the research field of cerebral asymmetries.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"208 ","pages":"211-230"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Physiology of neuroglia of the central nervous system.","authors":"Alexei Verkhratsky, Alexey Semyanov","doi":"10.1016/B978-0-443-19104-6.00005-X","DOIUrl":"10.1016/B978-0-443-19104-6.00005-X","url":null,"abstract":"<p><p>Neuroglia of the central nervous system (CNS) are a diverse and highly heterogeneous population of cells of ectodermal, neuroepithelial origin (macroglia, that includes astroglia and oligodendroglia) and mesodermal, myeloid origin (microglia). Neuroglia are primary homeostatic cells of the CNS, responsible for the support, defense, and protection of the nervous tissue. The extended class of astroglia (which includes numerous parenchymal astrocytes, such as protoplasmic, fibrous, velate, marginal, etc., radial astrocytes such as Bergmann glia, Muller glia, etc., and ependymoglia lining the walls of brain ventricles and central canal of the spinal cord) is primarily responsible for overall homeostasis of the nervous tissue. Astroglial cells control homeostasis of ions, neurotransmitters, hormones, metabolites, and are responsible for neuroprotection and defense of the CNS. Oligodendroglia provide for myelination of axons, hence supporting and sustaining CNS connectome. Microglia are tissue macrophages adapted to the CNS environment which contribute to the host of physiologic functions including regulation of synaptic connectivity through synaptic pruning, regulation of neurogenesis, and even modifying neuronal excitability. Neuroglial cells express numerous receptors, transporters, and channels that allow neuroglia to perceive and follow neuronal activity. Activation of these receptors triggers intracellular ionic signals that govern various homeostatic cascades underlying glial supportive and defensive capabilities. Ionic signaling therefore represents the substrate of glial excitability.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"209 ","pages":"69-91"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The cholinergic synapses.","authors":"Hermona Soreq, Adi Bar, Iddo Paldor","doi":"10.1016/B978-0-443-19088-9.00003-2","DOIUrl":"https://doi.org/10.1016/B978-0-443-19088-9.00003-2","url":null,"abstract":"<p><p>Acetylcholine (ACh) is a leading regulatory neurotransmitter in the nervous system, which functions both directly and as modulator of other neurotransmitters. It is found in the central and peripheral nervous system, as well as in the autonomic system-both sympathetic and parasympathetic. In the central nervous system (CNS), ACh functions not only as a neurotransmitter, but also as a modulator of cognitive functions, including long-term and short-term memory, limbic activation, and alertness. No process in the mammalian body can commence without its participation.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"211 ","pages":"23-35"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Memory network and cognitive reserve are associated with preserved and stimulated cholinergic neurotransmission.","authors":"Cecilia Boccalini, Daniela Perani, Valentina Garibotto","doi":"10.1016/B978-0-443-19088-9.00014-7","DOIUrl":"https://doi.org/10.1016/B978-0-443-19088-9.00014-7","url":null,"abstract":"<p><p>The cholinergic system plays a central role in cognition and neural function, and, in Alzheimer disease (AD) and Lewy body disease (LBD), it has profound implications for cognitive impairment and dementia. The cholinergic forebrain pathway, innervating the neocortex and limbic system, is crucial for learning, memory, and other essential aspects of cognition and plays a wider role in promoting neuronal plasticity. Given the neuroplasticity processes characterizing the cholinergic regions, this system may be sensitive to modulatory phenomena such as cognitive reserve (CR). The concept of CR has been introduced to account for the fact that individual clinical presentation might be milder than expected based on neuropathology. This mismatch can be explained by individual brain reserve (BR) buildup on life experiences, lifestyles, and neurobiologic factors that are associated with resilience. Sparse findings exist suggesting that the CR might result in an increased or preserved function of the cholinergic system in AD patients, and compensatory mechanisms in the early stages of LBD. The limited availability of effective treatment for neurodegenerative dementia emphasizes the importance of CR and BR, as they play a major role in delaying or slowing disease onset and progression. This chapter will describe the involvement of the cholinergic system in neurodegenerative diseases and the tools for the in vivo assessment, focusing specifically on the evidence suggesting the possibility of its modulation by CR.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"211 ","pages":"137-153"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The involvement of the cholinergic system in Parkinson disease.","authors":"Jacopo Pasquini, David J Brooks, Nicola Pavese","doi":"10.1016/B978-0-443-19088-9.00001-9","DOIUrl":"https://doi.org/10.1016/B978-0-443-19088-9.00001-9","url":null,"abstract":"<p><p>In Parkinson disease (PD), cholinergic dysfunction develops in the early stages of the neurodegenerative process and progresses over time. Basal forebrain cholinergic system dysfunction is historically linked to cognitive decline in the dementia spectrum, and its pathophysiologic role in PD-related cognitive impairment has now been well established. However, cholinergic system dysfunction is also linked to several other manifestations of PD, such as gait difficulties, REM sleep behavior disorder (RBD), neuropsychiatric manifestations such as depression and visual hallucinations, and olfactory dysfunction. Furthermore, disruption of the striatal intrinsic cholinergic system, which modulates dopamine release, has been linked to cardinal motor manifestations and dyskinesia. Manifestations of cognitive decline, gait problems, falls, and RBD tend to cluster in a subset of people with PD, so that a \"cholinergic phenotype\" has been proposed. In this chapter, the involvement of the cholinergic system and its clinical correlates in PD will be discussed.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"211 ","pages":"215-229"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuroglia in anxiety disorders.","authors":"Robin E Bonomi, Robert Pietrzak, Kelly P Cosgrove","doi":"10.1016/B978-0-443-19102-2.00008-9","DOIUrl":"10.1016/B978-0-443-19102-2.00008-9","url":null,"abstract":"<p><p>Anxiety disorders are some of the most prevalent in the world and are extraordinarily debilitating to many individuals, costing millions in disability. One of the most disabling is posttraumatic stress disorder (Snijders et al., 2020). Understanding the pathophysiology of these illnesses further and the cell types involved will allow better targeting of treatments. Glial cells, encompassing microglia, astrocytes, and oligodendrocytes, play critical roles in the pathophysiology of PTSD and other anxiety illnesses. Each of these cell types interacts with aspects of neuro-epigenetics, neuroimmune, and neuronal signaling and may contribute to the pathophysiology of anxiety illnesses. This chapter covers the literature on the role of glial cells in the neurobiology and pathology of anxiety disorders, more specifically PTSD. PTSD is one of the most debilitating anxiety disorders and one of the most complicated from a neurobiologic perspective. This chapter also features a discussion surrounding the current state of treatment and some of the hypothesized mechanisms for novel treatments including tetrahydrocannabidiol and 3,4-methylenedioxymethamphetamine. Finally, thoughts on the future directions for precision treatment and pharmacologic development with a focus on neuroglia are undertaken.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"210 ","pages":"335-346"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuroglia in mood disorders.","authors":"Gijsje J L J Snijders, Frederieke A J Gigase","doi":"10.1016/B978-0-443-19102-2.00010-7","DOIUrl":"10.1016/B978-0-443-19102-2.00010-7","url":null,"abstract":"<p><p>Multiple lines of evidence indicate that mood disorders, such as major depressive and bipolar disorder, are associated with abnormalities in neuroglial cells. This chapter discusses the existing literature investigating the potential role of astrocytes, oligodendrocytes, and microglia in mood pathology. We will describe evidence from in vivo imaging, postmortem, animal models based on (stress) paradigms that mimic depressive-like behavior, and biomarker studies in blood and cerebrospinal fluid in patients with mood disorders. The effect of medication used in the treatment of mood disorders, such as antidepressants and lithium, on glial function is discussed. Lastly, we highlight the most relevant findings about potential deficiencies in glia-glia crosstalk in mood disorders. Overall, decreased astrocyte and oligodendrocyte density and expression and microglial changes in homeostatic functions have frequently been put forward in MDD pathology. Studies of BD report similar findings to some extent; however, the evidence is less well established. Together, these findings are suggestive of reduced glial cell function leading to potential white matter abnormalities, glutamate dysregulation, disrupted neuronal functioning, and neurotransmission. However, more research is required to better understand the exact mechanisms underlying glial cell contributions to mood disorder development.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"210 ","pages":"287-302"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unraveling the complexity of microglial responses in traumatic brain and spinal cord injury.","authors":"Rebecca J Henry, David J Loane","doi":"10.1016/B978-0-443-19102-2.00015-6","DOIUrl":"10.1016/B978-0-443-19102-2.00015-6","url":null,"abstract":"<p><p>Microglia, the resident innate immune cells of the central nervous system (CNS), play an important role in neuroimmune signaling, neuroprotection, and neuroinflammation. In the healthy CNS, microglia adopt a surveillant and antiinflammatory phenotype characterized by a ramified scanning morphology that maintains CNS homeostasis. In response to acquired insults, such as traumatic brain injury (TBI) or spinal cord injury (SCI), microglia undergo a dramatic morphologic and functional switch to that of a reactive state. This microglial switch is initially protective and supports the return of the injured tissue to a physiologic homeostatic state. However, there is now a significant body of evidence that both TBI and SCI can result in a chronic state of microglial activation, which contributes to neurodegeneration and impairments in long-term neurologic outcomes in humans and animal models. In this review, we discuss the complex role of microglia in the pathophysiology of TBI and SCI, and recent advancements in knowledge of microglial phenotypic states in the injured CNS. Furthermore, we highlight novel therapeutic strategies targeting chronic microglial responses in experimental models and discuss how they may ultimately be translated to the clinic for human brain and SCI.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"210 ","pages":"113-132"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniele Mattei, Dilansu Guneykaya, Bilge Ugursu, Alice Buonfiglioli
{"title":"From womb to world: The interplay between maternal immune activation, neuroglia, and neurodevelopment.","authors":"Daniele Mattei, Dilansu Guneykaya, Bilge Ugursu, Alice Buonfiglioli","doi":"10.1016/B978-0-443-19102-2.00028-4","DOIUrl":"10.1016/B978-0-443-19102-2.00028-4","url":null,"abstract":"<p><p>This chapter introduces and discusses maternal immune activation (MIA) as a contributing factor in increasing the risk of neurodevelopmental disorders, particularly in relation to its interactions with neuroglia. Here we first provide an overview of the neuroglia-astroglia, oligodendroglia, microglia, and radial glial cells-and their important role during early brain development and in adulthood. We then present and discuss MIA, followed by a critical overview of inflammatory molecules and temporal stages associated to maternal inflammation during pregnancy. We provide an overview of animal and human models used to mimic and study MIA. Furthermore, we review the possible interaction between MIA and neuroglia, focusing on the current advances in both modeling and therapeutics. Additionally, we discuss and provide preliminary and interesting insights into the most recent pandemic, COVID-19, and how the infection may be associated to MIA and increased risk for neurodevelopmental disorders. Finally, we provide a critical overview of challenges and future opportunities to study how MIA may contribute to higher risk of developing neurodevelopmental disorders.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"210 ","pages":"269-285"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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