Neuroscientist最新文献

{"title":"Ferroptosis in Neurological Disease.","authors":"Samuel David,&nbsp;Fari Ryan,&nbsp;Priya Jhelum,&nbsp;Antje Kroner","doi":"10.1177/10738584221100183","DOIUrl":"10.1177/10738584221100183","url":null,"abstract":"<p><p>Iron accumulation in the CNS occurs in many neurological disorders. It can contribute to neuropathology as iron is a redox-active metal that can generate free radicals. The reasons for the iron buildup in these conditions are varied and depend on which aspects of iron influx, efflux, or sequestration that help maintain iron homeostasis are dysregulated. Iron was shown recently to induce cell death and damage via lipid peroxidation under conditions in which there is deficient glutathione-dependent antioxidant defense. This form of cell death is called <i>ferroptosis</i>. Iron chelation has had limited success in the treatment of neurological disease. There is therefore much interest in ferroptosis as it potentially offers new drugs that could be more effective in reducing iron-mediated lipid peroxidation within the lipid-rich environment of the CNS. In this review, we focus on the molecular mechanisms that induce ferroptosis. We also address how iron enters and leaves the CNS, as well as the evidence for ferroptosis in several neurological disorders. Finally, we highlight biomarkers of ferroptosis and potential therapeutic strategies.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 5","pages":"591-615"},"PeriodicalIF":5.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10437238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dual Nature of Microglia in Alzheimer's Disease: A Microglia-Neuron Crosstalk Perspective.","authors":"Zhen Xie,&nbsp;Jie Meng,&nbsp;Zhou Wu,&nbsp;Hiroshi Nakanishi,&nbsp;Yoshinori Hayashi,&nbsp;Wei Kong,&nbsp;Fei Lan,&nbsp;Narengaowa,&nbsp;Qinghu Yang,&nbsp;Hong Qing,&nbsp;Junjun Ni","doi":"10.1177/10738584211070273","DOIUrl":"10.1177/10738584211070273","url":null,"abstract":"<p><p>Microglia are critical players in the neuroimmune system, and their involvement in Alzheimer's disease (AD) pathogenesis is increasingly being recognized. However, whether microglia play a positive or negative role in AD remains largely controversial and the precise molecular targets for intervention are not well defined. This partly results from the opposing roles of microglia in AD pathology, and is mainly reflected in the microglia-neuron interaction. Microglia can prune synapses resulting in excessive synapse loss and neuronal dysfunction, but they can also promote synapse formation, enhancing neural network plasticity. Neuroimmune crosstalk accelerates microglial activation, which induces neuron death and enhances the microglial phagocytosis of β-amyloid to protect neurons. Moreover, microglia have dual opposing roles in developing the major pathological features in AD, such as amyloid deposition and blood-brain barrier permeability. This review summarizes the dual opposing role of microglia in AD from the perspective of the interaction between neurons and microglia. Additionally, current AD treatments targeting microglia and the advantages and disadvantages of developing microglia-targeted therapeutic strategies are discussed.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 5","pages":"616-638"},"PeriodicalIF":5.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10064498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gap Junctions in the Brain: Hardwired but Functionally Versatile.","authors":"Rafael Gutiérrez","doi":"10.1177/10738584221120804","DOIUrl":"10.1177/10738584221120804","url":null,"abstract":"<p><p>Gap junctions between neurons of the brain are thought to be present in only certain cell types, and they mostly connect dendrites, somata, and axons. Synapses with gap junctions serve bidirectional metabolic and electrical coupling between connected neuronal compartments. Although plasticity of electrical synapses has been described, recent evidence of the presence of silent, but activatable, gap junctions suggests that electrical nodes in a neuronal circuit can be added or suppressed by changes in the synaptic microenvironment. This opens the possibility of reconfiguration of neuronal ensembles in response to activity. Moreover, the coexistence of gap junctions in a glutamatergic synapse may add electric and metabolic coupling to a neuronal aggregate and may serve to constitute primed ensembles within a higher-order neural network. The interaction of chemical with electrical synapses should be further explored to find, especially, emerging properties of neuronal ensembles. It will be worth to reexamine in a new light the \"functional\" implications of the \"anatomic\" concepts: \"continuity\" and \"contiguity,\" which were championed by Golgi and Ramón y Cajal, respectively. In any case, exploring the versatility of the gap junctions will likely enrich the heuristic aspects of the neural and network postulates.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 5","pages":"554-568"},"PeriodicalIF":5.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10065048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Memory: Synaptic or Cellular, That Is the Question.","authors":"Yuri I Arshavsky","doi":"10.1177/10738584221086488","DOIUrl":"10.1177/10738584221086488","url":null,"abstract":"<p><p>According to the commonly accepted opinion, memory engrams are formed and stored at the level of neural networks due to a change in the strength of synaptic connections between neurons. This hypothesis of synaptic plasticity (HSP), formulated by Donald Hebb in the 1940s, continues to dominate the directions of experimental studies and the interpretations of experimental results in the field. The universal acceptance of the HSP has transformed it from a hypothesis into an incontrovertible theory. In this article, I show that the entire body of experimental and clinical data obtained in studies of long-term memory in mammals and humans is inconsistent with the HSP. Instead, these data suggest that long-term memory is formed and stored at the intracellular level where it is reliably protected from ongoing synaptic activity, including pathological epileptic activity. It seems that the generally accepted HSP became a serious obstacle to understanding the mechanisms of memory and that progress in this field requires rethinking this doctrine and shifting experimental efforts toward exploring the intracellular mechanisms.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 5","pages":"538-553"},"PeriodicalIF":5.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10417655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenosine and Astrocytes Control Critical Periods of Neural Plasticity.","authors":"Irene Martínez-Gallego,&nbsp;Antonio Rodríguez-Moreno","doi":"10.1177/10738584221126632","DOIUrl":"10.1177/10738584221126632","url":null,"abstract":"<p><p>Windows of plasticity are fundamental for the correct formation of definitive brain circuits; these periods drive sensory and motor learning during development and ultimately learning and memory in adults. However, establishing windows of plasticity also imposes limitations on the central nervous system in terms of its capacity to recover from injury. Recent evidence highlights the important role that astrocytes and adenosine seem to play in controlling the duration of these critical periods of plasticity.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 5","pages":"532-537"},"PeriodicalIF":5.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10437984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perspectives on Neuroscience and Behavior.","authors":"","doi":"10.1177/10738584231190621","DOIUrl":"10.1177/10738584231190621","url":null,"abstract":"The serendipitous discovery that lithium could treat bipolar disorder (BD) was published in 1949. In 1967, a published diagrammatic display of the clinical course of 88 patients with BP treated with lithium for one to six years depicted lithium’s extremely robust efficacy in preventing BP episodes, but there was also considerable variability across patients. In 1970, a five-month double-blind withdrawal study of lithium was published in which half of stable 50 patients with BD and 34 patients with recurrent depression were switched from lithium to placebo. Relapse occurred in 21 on placebo and none on lithium, which unequivocally demonstrated the robust efficacy of lithium in preventing relapse in BD and recurrent depression. Over the past 53 years, there have been an extensive number of studies attempting to discover the mechanism by which lithium produces such an important therapeutic effect. Now, in an outstanding and penetrating mechanistic study, it has been found that in two mouse models of ankyrin-G (AnkG) deficiency that displayed decreased dendritic complexity and decreased dendritic spine numbers in cortical neurons, lithium treatment corrected both abnormalities in both models. In the cortical neuron culture model with AnkG knockdown, a selective glycogen synthase kinase 3β (GSK3β) inhibitor rescued the spine morphology defects but not the dendritic complexity, and forskolin, which increases cAMP, rescued the dendritic complexity but not the spine morphology. A synergistic effect of both drugs was required to correct both the spine morphology and dendritic complexity (Piguel and others 2023). These findings are an important advance, since the ANK3 gene is linked to BD, single-nucleotide polymorphisms within the ANK3 regulatory domains have been found to be associated with lithium response in patients with BP, and mouse ANK3 knockout models have behavioral features like BD that respond to lithium treatment. Lithium directly or indirectly, through autoinhibition, acts to inhibit GSK3β, and it rescues several behavioral deficits like BD in ANKG knockout mice. In addition, lithium increases cAMP levels in frontal cortex. It should now be possible to assess the effects of lithium in individuals with BP who have genetic AnkG abnormalities to see if they have a more beneficial therapeutic response. Most important, the discovery that lithium’s mechanism of action involves both GSK3β inhibition and increased cAMP can help guide new research to discover alternatives to lithium, because lithium has so many toxic side effects.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 5","pages":"517"},"PeriodicalIF":5.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10121498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perineuronal Nets: Subtle Structures with Large Implications.","authors":"Héctor Carceller,&nbsp;Yaiza Gramuntell,&nbsp;Patrycja Klimczak,&nbsp;Juan Nacher","doi":"10.1177/10738584221106346","DOIUrl":"10.1177/10738584221106346","url":null,"abstract":"<p><p>Perineuronal nets (PNNs) are specialized structures of the extracellular matrix that surround the soma and proximal dendrites of certain neurons in the central nervous system, particularly parvalbumin-expressing interneurons. Their appearance overlaps the maturation of neuronal circuits and the closure of critical periods in different regions of the brain, setting their connectivity and abruptly reducing their plasticity. As a consequence, the digestion of PNNs, as well as the removal or manipulation of their components, leads to a boost in this plasticity and can play a key role in the functional recovery from different insults and in the etiopathology of certain neurologic and psychiatric disorders. Here we review the structure, composition, and distribution of PNNs and their variation throughout the evolutive scale. We also discuss methodological approaches to study these structures. The function of PNNs during neurodevelopment and adulthood is discussed, as well as the influence of intrinsic and extrinsic factors on these specialized regions of the extracellular matrix. Finally, we review current data on alterations in PNNs described in diseases of the central nervous system (CNS), focusing on psychiatric disorders. Together, all the data available point to the PNNs as a promising target to understand the physiology and pathologic conditions of the CNS.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 5","pages":"569-590"},"PeriodicalIF":5.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10417661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"José Manuel Rodríguez Delgado, Walter Freeman, and Psychosurgery: A Study in Contrasts.","authors":"Joseph J Fins,&nbsp;John S Vernaglia","doi":"10.1177/10738584221086603","DOIUrl":"10.1177/10738584221086603","url":null,"abstract":"<p><p>History has conflated the legacies of José Manuel Rodríguez Delgado and Walter Freeman, midcentury proponents of somatic therapies for neuropsychiatric conditions. Both gained notoriety: Delgado after he appeared on the front page of the <i>New York Times</i> having used his <i>stimoceiver</i> to stop a charging bull in Spain; Freeman as the proponent of lobotomy. Both were the object of critique by the antipsychiatry movement and those who felt that their methods and objectives posed a threat to personal liberty. Using archival sources, we demonstrate that this conflation is a misrepresentation of the historical record and that their methods, objectives, ethics, and philosophical commitments differed widely. Accurate knowledge about historical antecedents is a predicate for ethical analysis and becomes especially relevant information as neuroscience develops circuit-based treatments for conditions such as Parkinson disease, depression, and brain injury. Part of that corrective is to counter the conflation of Delgado's and Freeman's life and work. Appreciating their distinctive legacies can help guide neuropsychiatric research done today that might yet haunt future generations.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 5","pages":"518-531"},"PeriodicalIF":5.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10436749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prefrontal Cortical Control of Anxiety: Recent Advances.","authors":"Nancy R Mack,&nbsp;Suixin Deng,&nbsp;Sha-Sha Yang,&nbsp;Yousheng Shu,&nbsp;Wen-Jun Gao","doi":"10.1177/10738584211069071","DOIUrl":"https://doi.org/10.1177/10738584211069071","url":null,"abstract":"<p><p>Dysfunction in the prefrontal cortex is commonly implicated in anxiety disorders, but the mechanisms remain unclear. Approach-avoidance conflict tasks have been extensively used in animal research to better understand how changes in neural activity within the prefrontal cortex contribute to avoidance behaviors, which are believed to play a major role in the maintenance of anxiety disorders. In this article, we first review studies utilizing <i>in vivo</i> electrophysiology to reveal the relationship between changes in neural activity and avoidance behavior in rodents. We then review recent studies that take advantage of optical and genetic techniques to test the unique contribution of specific prefrontal cortex circuits and cell types to the control of anxiety-related avoidance behaviors. This new body of work reveals that behavior during approach-avoidance conflict is dynamically modulated by individual cell types, distinct neural pathways, and specific oscillatory frequencies. The integration of these different pathways, particularly as mediated by interactions between excitatory and inhibitory neurons, represents an exciting opportunity for the future of understanding anxiety.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"488-505"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869286/pdf/nihms-1863656.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9913211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ongoing Brain Activity and Its Role in Cognition: Dual versus Baseline Models.","authors":"Georg Northoff,&nbsp;Deniz Vatansever,&nbsp;Andrea Scalabrini,&nbsp;Emmanuel A Stamatakis","doi":"10.1177/10738584221081752","DOIUrl":"https://doi.org/10.1177/10738584221081752","url":null,"abstract":"<p><p>What is the role of the brain's ongoing activity for cognition? The predominant perspectives associate ongoing brain activity with resting state, the default-mode network (DMN), and internally oriented mentation. This triad is often contrasted with task states, non-DMN brain networks, and externally oriented mentation, together comprising a \"dual model\" of brain and cognition. In opposition to this duality, however, we propose that ongoing brain activity serves as a neuronal baseline; this builds upon Raichle's original search for the default mode of brain function that extended beyond the canonical default-mode brain regions. That entails what we refer to as the \"baseline model.\" Akin to an internal biological clock for the rest of the organism, the ongoing brain activity may serve as an internal point of reference or standard by providing a shared neural code for the brain's rest as well as task states, including their associated cognition. Such shared neural code is manifest in the spatiotemporal organization of the brain's ongoing activity, including its global signal topography and dynamics like intrinsic neural timescales. We conclude that recent empirical evidence supports a baseline model over the dual model; the ongoing activity provides a global shared neural code that allows integrating the brain's rest and task states, its DMN and non-DMN, and internally and externally oriented cognition.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"393-420"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10052369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}