Handbook of clinical neurology最新文献

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CNS muscarinic receptors and muscarinic receptor agonists in Alzheimer disease treatment. 中枢神经系统毒蕈碱受体和毒蕈碱受体激动剂治疗阿尔茨海默病。
Handbook of clinical neurology Pub Date : 2025-01-01 DOI: 10.1016/B978-0-443-19088-9.00016-0
Abraham Fisher, Allan I Levey
{"title":"CNS muscarinic receptors and muscarinic receptor agonists in Alzheimer disease treatment.","authors":"Abraham Fisher, Allan I Levey","doi":"10.1016/B978-0-443-19088-9.00016-0","DOIUrl":"https://doi.org/10.1016/B978-0-443-19088-9.00016-0","url":null,"abstract":"<p><p>This review explores the main aspects that form the basis of the cholinergic-oriented treatment of Alzheimer disease. Muscarinic acetylcholine receptor subtypes in the brain and periphery are discussed. It includes a new and updated overview of the involvement of muscarinic receptors in Alzheimer disease and the recent development of new and highly selective M1 muscarinic receptor agonists with disease-modifying potential. Activation of the M1 muscarinic receptor is a rational therapeutic strategy for the treatment of schizophrenia and Alzheimer disease, as this receptor plays a pivotal role in modulating cognitive deficits and the pathology of the disease. Such activation can be achieved through M1 allosteric and bitopic muscarinic agonists, M1 positive allosteric modulators (M1 PAMs), and direct-acting M1 muscarinic orthosteric agonists. The efficacy of M1 PAMs depends on acetylcholine, which declines in Alzheimer disease as postsynaptic neurons lose cholinergic input from the basal forebrain. On the other hand, the activity of M1 muscarinic orthosteric agonists is independent of the functional or anatomic integrity of presynaptic cholinergic terminals, and likely retain efficacy as the disease progresses, even after presynaptic degeneration of cholinergic fibers. Based on the acceptance criteria for a preferred M1 muscarinic agonist for the treatment of AD, aiming for efficacy, specificity, and safety in clinical use, few M1 muscarinic agonists fulfill these requirements, such as orthosteric M1 agonists-cevimeline (aka AF102B), the first FDA-approved M1 agonist, and NSC001 (aka AF267B). The pros and cons of various muscarinic agonists developed are critically discussed in comparison to these drugs. The review proposes new alternatives to cholinergic therapy, particularly selective M1 muscarinic drugs, that should be designed to amplify its clinical effect and supplement the disease-modifying effect of new treatments to slow down or arrest disease progression.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"211 ","pages":"161-184"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992950","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}
引用次数: 0
The lateralization of reading. 阅读的偏侧化。
Handbook of clinical neurology Pub Date : 2025-01-01 DOI: 10.1016/B978-0-443-15646-5.00012-9
Jason J S Barton, Andrea Albonico, Randi Starrfelt
{"title":"The lateralization of reading.","authors":"Jason J S Barton, Andrea Albonico, Randi Starrfelt","doi":"10.1016/B978-0-443-15646-5.00012-9","DOIUrl":"10.1016/B978-0-443-15646-5.00012-9","url":null,"abstract":"<p><p>Reports in the 1890s described reading disorders from left hemisphere damage. Subsequent work converging from a variety of research approaches have confirmed a strong dependence of reading on the left ventral occipitotemporal cortex, though there is also evidence for some reading capacity of the right hemisphere. The development of this leftward bias parallels reading acquisition in children and adults and is blunted in developmental dyslexia. Several structural and functional hypotheses have been advanced to explain why reading lateralizes to the left. In the second half of this review we explore the extension of these findings to other forms of reading. Most reading studies used the alphabetic scripts of Europe but there are many writing systems. Comparisons with logographic scripts such as Chinese and kanji have revealed subtle differences. Also, while we often think of reading as the extraction of verbal language from written text, it can be broadened to other types of information extraction from symbols. Reading can occur with visual stimuli that are not written text, as with sign language in the deaf and lip-reading, and with non-visual stimuli that are textual, as with Braille. Musical notation and number reading are other text-based visual forms of reading that do not involve words. Overall, most studies show that the left ventral occipitotemporal cortex is involved in processing these diverse types of reading, with variable contributions from the right hemisphere.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"208 ","pages":"301-325"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614672","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}
引用次数: 0
The cholinotrophic system in Down syndrome. 唐氏综合症的胆碱营养系统。
Handbook of clinical neurology Pub Date : 2025-01-01 DOI: 10.1016/B978-0-443-19088-9.00017-2
Elliott J Mufson, Sylvia E Perez
{"title":"The cholinotrophic system in Down syndrome.","authors":"Elliott J Mufson, Sylvia E Perez","doi":"10.1016/B978-0-443-19088-9.00017-2","DOIUrl":"https://doi.org/10.1016/B978-0-443-19088-9.00017-2","url":null,"abstract":"<p><p>Cholinergic basal forebrain (CBF) projection neurons within the nucleus basalis and striatal cholinergic interneurons degenerate in individuals with Down syndrome (DS). However, the neuropathobiology of these diverse cholinergic phenotypes remains underinvestigated. This review summarizes the alterations of cholinergic, neurotrophic survival and cell death factors as well as tau pathology and amyloidopathy, and their effects upon these cell types in DS. In trisomy, the developing cholinergic system remains stable, whereas the neurotrophic receptors are compromised between control and DS cases. Both cholinergic neuronal phenotypes display severe cellular degeneration in both adult and the aged people with DS. Although developing cholinergic striatal neurons display a similar morphology between phenotypes, cholinergic striatal neurons appear dystrophic in adults with DS. Both cholinergic cell types display tau tangle pathology in elders with DS. Novel findings suggest that alterations in plasma and cerebral spinal fluid levels of proNGF, NGF metabolites, and select classes of neuronal genes are potential biomarkers to distinguish nondemented from demented people with DS. Compounds that target cholinergic pathways, TrkA agonists, p75<sup>NTR</sup>/proNGF small molecular antagonists, NGF metabolites, and select gene ontology classes are potential targets to slow degeneration of the CBF memory connectome in DS with translation to AD.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"211 ","pages":"185-213"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963254","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}
引用次数: 0
Neuroglia in suicide. 自杀中的神经胶质细胞。
Handbook of clinical neurology Pub Date : 2025-01-01 DOI: 10.1016/B978-0-443-19102-2.00018-1
Lin Zhang, Dick F Swaab
{"title":"Neuroglia in suicide.","authors":"Lin Zhang, Dick F Swaab","doi":"10.1016/B978-0-443-19102-2.00018-1","DOIUrl":"10.1016/B978-0-443-19102-2.00018-1","url":null,"abstract":"<p><p>Suicide is the worst outcome for many neuropsychiatric disorders having a high social and economic burden. There is a great need to determine the neurobiologic background of the etiopathogenesis and resilience toward suicide and to find novel pharmacologic strategies to treat suicidal behaviors. Neuroglia have been found to actively participate in the regulation of many cerebral functions, but it is debated whether these cells are structurally or functionally involved in the neuropathology of suicide, or merely follow the changes of comorbid psychiatric disorders. The purpose of this chapter is to review the scattered literature on the involvement of neuroglia in suicide and to describe how these cells might be responsive to the current pharmacologic interventions. We describe the different biological features of neuroglia in relation to suicide and the underlying psychiatric disorders, the molecular commonalities of neuroglial alterations in suicide across different psychiatric disorders, and the evidence for morphologic neuroglia changes in relation to the severity and resilience of suicide. Illuminating the mechanisms by which neuroglia are involved in suicide may ultimately lead to the development of suicide-related biomarkers and novel therapies for suicide prevention.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"210 ","pages":"371-379"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729802","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}
引用次数: 0
Neuroglia pathology in genetic and epigenetic disorders of the central nervous system. 中枢神经系统遗传和表观遗传疾病中的神经胶质病理。
Handbook of clinical neurology Pub Date : 2025-01-01 DOI: 10.1016/B978-0-443-19102-2.00003-X
Harvey B Sarnat, Vijayaraghava T S Rao
{"title":"Neuroglia pathology in genetic and epigenetic disorders of the central nervous system.","authors":"Harvey B Sarnat, Vijayaraghava T S Rao","doi":"10.1016/B978-0-443-19102-2.00003-X","DOIUrl":"10.1016/B978-0-443-19102-2.00003-X","url":null,"abstract":"<p><p>Glial cells are increasingly recognized for their important interactions with both developing and mature neurons, in particular for maintenance of dendritic ramifications and spines, synapses, and neurotransmitter uptake. MicroRNA abnormalities are demonstrated in individual astrocytes with alterations in neurological diseases. Alexander disease is a prototype astrocytic disease because of genetically altered glial fibrillary acidic protein (GFAP) filaments. Other genetic diseases are now recognized as involving glial cells in their pathogenesis: Rett, Fragile-X, Aicardi-Goutières, and Down syndromes, as well as epigenetic effects in the mechanism of fetal alcohol spectrum disorder. Many involve glial production of cytokines and neuroinflammation. Microglia also may contribute. The heat-shock protein α-B-crystallin is expressed in the Rosenthal fibers of Alexander disease, in which the molecular structure of GFAP is altered, in astrocytes secreting neurotoxic cytokines, and focally at or near epileptic foci. Satellite glial cells adherent to neuronal soma are frequent and diagnostically nonspecific but may contribute to neuronal degeneration, especially of hypermetabolic epileptogenic neurons. Glial cells have distorted size and morphology in mTOR malformations. Failure of glial apoptosis in the fetal lamina terminalis is the likely pathogenesis of callosal agenesis and of other cerebral dysgeneses.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"210 ","pages":"87-99"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729804","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}
引用次数: 0
Neuroglial responses to bacterial, viral, and fungal neuroinfections. 神经胶质细胞对细菌、病毒和真菌神经感染的反应。
Handbook of clinical neurology Pub Date : 2025-01-01 DOI: 10.1016/B978-0-443-19102-2.00027-2
Ifeoluwa Awogbindin, Eva ŠimonČiČová, Virginie Vidal, Chantaille Ash, Marie-Eve Tremblay
{"title":"Neuroglial responses to bacterial, viral, and fungal neuroinfections.","authors":"Ifeoluwa Awogbindin, Eva ŠimonČiČová, Virginie Vidal, Chantaille Ash, Marie-Eve Tremblay","doi":"10.1016/B978-0-443-19102-2.00027-2","DOIUrl":"10.1016/B978-0-443-19102-2.00027-2","url":null,"abstract":"<p><p>Evidence regarding the host's response to peripheral pathogens in humans abound, whereas studies on the pathogenesis of central nervous system-penetrating infections are relatively scarce. However, given the spate of epidemic and pandemic neuroinfections in the 21st century, the field has experienced a renewed interest lately. This chapter discusses a timely and exciting topic on the roles of glial cells, mainly microglia and astrocytes, in neuroinvasive infections. This chapter considered fungal, viral, and bacterial neuroinfections, X-raying their neuroinvasiveness, neurotropism, and neurovirulence before focusing on specific examples notable for each category, including Escherichia coli, Cryptococcus neoformans, and SARS-CoV-2. These infections are renowned worldwide for a high case-fatality rate, leaving many survivors with life-long morbidity and others with a bleak future neurologic prognosis. Importantly, the chapter discusses possible ways microglia and astrocytes are culpable in these infections and provides approaches by which they can be manipulated for therapeutic purposes, identifying viable research gaps in the process. Additionally, it offers a synopsis of ongoing works considering microglial selective targeting to attenuate the pathology, morbidity, and mortality associated with these neuroinfections. Considering that microglia and astrocytes are first responders in the central nervous system, targeting these glial cells could be the game changer in managing existing and emerging neuroinvasive infections.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"210 ","pages":"213-238"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729805","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}
引用次数: 0
Hemispheric asymmetries in episodic memory. 情景记忆中的半球不对称。
Handbook of clinical neurology Pub Date : 2025-01-01 DOI: 10.1016/B978-0-443-15646-5.00023-3
Gian Daniele Zannino, Giovanni Augusto Carlesimo
{"title":"Hemispheric asymmetries in episodic memory.","authors":"Gian Daniele Zannino, Giovanni Augusto Carlesimo","doi":"10.1016/B978-0-443-15646-5.00023-3","DOIUrl":"10.1016/B978-0-443-15646-5.00023-3","url":null,"abstract":"<p><p>The term \"episodic memory\" refers to our ability to remember past personal experiences. This ability is severely disrupted following bilateral damage to a dedicated neural substrate located symmetrically in the mesial temporal lobes. Milder deficits are also observed following unilateral damage to the same structures. In this chapter, we contrast memory deficits after left and right mesiotemporal damage and review some of the hypotheses proposed to account for the observed differences. As proposed by other authors (e.g., Binder et al., 2010), the observed lesion side effects in memory profiles after unilateral brain damage do not directly reflect specialization across the two symmetric memory substrates. Rather, they depend on the different kinds of information each of the two mesiotemporal structures receives from the ipsilateral hemisphere where other non-memory-specific cognitive systems are asymmetrically housed. In particular, this chapter outlines the role of language, working memory, and visuospatial processes in accounting for side effects in memory profiles. This is because all these systems greatly contribute to the functioning of episodic memory and also show a variable extent of lateralization in the human brain.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"208 ","pages":"449-460"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614385","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}
引用次数: 0
Single-cell omics and heterogeneity of neuroglial cells. 神经胶质细胞的单细胞组学和异质性。
Handbook of clinical neurology Pub Date : 2025-01-01 DOI: 10.1016/B978-0-443-19104-6.00013-9
Sylvie C Lahaie, Naama Brezner, Keith K Murai
{"title":"Single-cell omics and heterogeneity of neuroglial cells.","authors":"Sylvie C Lahaie, Naama Brezner, Keith K Murai","doi":"10.1016/B978-0-443-19104-6.00013-9","DOIUrl":"10.1016/B978-0-443-19104-6.00013-9","url":null,"abstract":"<p><p>Our bodies contain a rich diversity of cell types with unique physiologic properties. Interestingly, cells within our bodies contain the same DNA content, yet they can vary dramatically with respect to their molecular, structural, and functional properties. The need to better understand cellular complexity and diversity in biologic systems has led to a technical revolution in the field through the development of sophisticated single-cell \"omic\" approaches. This allows the investigation of the genome, epigenome, transcriptome, and proteome of individual cells derived from complex samples or tissues, such as nervous system tissue. These methods are allowing scientists to detect distinct cell populations and cellular states in different species (including rodent and human) and molecular transitions of cell populations across the lifespan. Recent studies have revealed that astrocytes, oligodendrocytes, and microglia exhibit greater molecular and functional heterogeneity than originally thought and innovative single-cell technologies have allowed a more comprehensive and less biased view of this cellular diversity. The chapter begins by providing a primer of single-cell transcriptomic and spatial transcriptomic approaches that have been particularly influential in uncovering single-cell diversity of neuroglial cells in the brain. It then takes a closer look at how these technologies have been pivotal in defining neuroglial cell subtypes and for determining their spatial relationships within the CNS. Then, it concludes with discussion of how the recent technical advances and discoveries have provoked new questions about the origin, organization, and functional purpose of diverse neuroglial cell subtypes.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"209 ","pages":"265-275"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691911","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}
引用次数: 0
Preface. 前言。
Handbook of clinical neurology Pub Date : 2025-01-01 DOI: 10.1016/B978-0-443-15646-5.09995-4
Costanza Papagno, Paul Corballis
{"title":"Preface.","authors":"Costanza Papagno, Paul Corballis","doi":"10.1016/B978-0-443-15646-5.09995-4","DOIUrl":"https://doi.org/10.1016/B978-0-443-15646-5.09995-4","url":null,"abstract":"","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"208 ","pages":"xiii-xiv"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614665","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}
引用次数: 0
In vitro models for human neuroglia. 人神经胶质细胞体外模型。
Handbook of clinical neurology Pub Date : 2025-01-01 DOI: 10.1016/B978-0-443-19104-6.00015-2
Bas Lendemeijer, Femke M S de Vrij
{"title":"In vitro models for human neuroglia.","authors":"Bas Lendemeijer, Femke M S de Vrij","doi":"10.1016/B978-0-443-19104-6.00015-2","DOIUrl":"10.1016/B978-0-443-19104-6.00015-2","url":null,"abstract":"<p><p>Neuroglia are a heterogenous population of cells in the nervous system. In the central nervous system, this group is classified into astrocytes, oligodendrocytes, and microglia. Neuroglia in the peripheral nervous system are divided into Schwann cells and enteric glia. These groups of cells display considerable differences in their developmental origin, morphology, function, and regional abundance. Compared to animal models, human neuroglia differ in their transcriptomic profile, morphology, and function. Investigating the physiology of healthy or diseased human neuroglia in vivo is challenging due to the inaccessibility of the tissue. Therefore, researchers have developed numerous in vitro models attempting to replicate the natural tissue environment. Earlier models made use of postmortem, postsurgical, or fetal tissue to establish human neuroglial cells in vitro, either as a pure population of the desired cell type or as organotypic slice cultures. Advancements in human stem cell differentiation techniques have greatly enhanced the possibilities for creating in vitro models of human neuroglia. This chapter provides an overview of the current models used to study the functioning and development of human neuroglia in vitro, both in health and disease.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"209 ","pages":"213-227"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692081","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}
引用次数: 0
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