Frontiers in Cellular Neuroscience最新文献

{"title":"Inflammatory changes in the choroid plexus following subarachnoid hemorrhage: the role of innate immune receptors and inflammatory molecules.","authors":"Peter Solár, Václav Brázda, Martin Bareš, Alemeh Zamani, Parisa EmamiAref, Andrea Joukal, Lucie Kubíčková, Erik Kročka, Klaudia Hašanová, Marek Joukal","doi":"10.3389/fncel.2024.1525415","DOIUrl":"10.3389/fncel.2024.1525415","url":null,"abstract":"<p><strong>Introduction: </strong>The choroid plexus is located in the cerebral ventricles. It consists of a stromal core and a single layer of cuboidal epithelial cells that forms the blood-cerebrospinal barrier. The main function of the choroid plexus is to produce cerebrospinal fluid. Subarachnoid hemorrhage due to aneurysm rupture is a devastating type of hemorrhagic stroke. Following subarachnoid hemorrhage, blood and the blood degradation products that disperse into the cerebrospinal fluid come in direct contact with choroid plexus epithelial cells. The aim of the current study was to elucidate the pathophysiological cascades responsible for the inflammatory reaction that is seen in the choroid plexus following subarachnoid hemorrhage.</p><p><strong>Methods: </strong>Subarachnoid hemorrhage was induced in rats by injecting non-heparinized autologous blood to the cisterna magna. Increased intracranial pressure following subarachnoid hemorrhage was modeled by using artificial cerebrospinal fluid instead of blood. Subarachnoid hemorrhage and artificial cerebrospinal fluid animals were left to survive for 1, 3, 7 and 14 days. Immunohistochemical staining of TLR4, TLR9, FPR2, CCL2, TNFα, IL-1β, CCR2 and CX3CR1 was performed on the cryostat sections of choroid plexus tissue. The level of TLR4, TLR9, FPR2, CCL2, TNFα, IL-1β was detected by measuring immunofluorescence intensity in randomly selected epithelial cells. The number of CCR2 and CX3CR1 positive cells per choroid plexus area was manually counted. Immunohistochemical changes were confirmed by Western blot analyses.</p><p><strong>Results: </strong>Immunohistochemical methods and Western blot showed increased levels of TLR9 and a slight increase in TLR4 and FRP2 following both subarachnoid hemorrhage as well as the application of artificial cerebrospinal fluid over time, although the individual periods were different. The levels of TNFα and IL-1β increased, while CCL2 level decreased slightly. Accumulation of macrophages positive for CCR2 and CX3CR1 was found in all periods after subarachnoid hemorrhage as well as after the application of artificial cerebrospinal fluid.</p><p><strong>Discussion: </strong>Our results suggest that the inflammation develops in the choroid plexus and blood-cerebrospinal fluid barrier in response to blood components as well as acutely increased intracranial pressure following subarachnoid hemorrhage. These pro-inflammatory changes include accumulation in the choroid plexus of pro-inflammatory cytokines, innate immune receptors, and monocyte-derived macrophages.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1525415"},"PeriodicalIF":4.2,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003284","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":"Noise-induced ribbon synapse loss in the mouse basal cochlear region does not reduce inner hair cell exocytosis.","authors":"David Oestreicher, Alfonso Mauro Malpede, Annalena Reitmeier, Carolin Paula Bräuer, Laura Schoch, Nicola Strenzke, Tina Pangrsic","doi":"10.3389/fncel.2024.1523978","DOIUrl":"10.3389/fncel.2024.1523978","url":null,"abstract":"<p><p>Noise-induced hearing loss is one of the most common forms of hearing loss in adults and also one of the most common occupational diseases. Extensive previous work has shown that the highly sensitive synapses of the inner hair cells (IHCs) may be the first target for irreparable damage and permanent loss in the noise-exposed cochlea, more precisely in the cochlear base. However, how such synaptic loss affects the synaptic physiology of the IHCs in this particularly vulnerable part of the cochlea has not yet been investigated. To address this question, we exposed 3-4-week-old C57BL/6J mice to 8-16 kHz noise for 2 h under isoflurane anesthesia. We then employed hearing measurements, immunohistochemistry and patch-clamp to assess IHC synaptic function. Two noise sound pressure levels (SPLs) were used to evoke acute hearing threshold elevations with different levels of recovery 2 weeks post-exposure. Regardless of noise intensity, the exposure resulted in a loss of approximately 25-36% of ribbon synapses in the basal portions of the cochlea that persisted 2 weeks after exposure. Perforated patch-clamp recordings were made in the IHCs of the basal regions of the cochlea where the greatest synaptic losses were observed. Depolarization-evoked calcium currents in IHCs 2 weeks after exposure were slightly but not significantly smaller as compared to controls from age-matched non-exposed animals. Exocytic changes monitored as changes in membrane capacitance did not follow that trend and remained similar to controls despite significant loss of ribbons, likely reflecting increased exocytosis at the remaining synapses. Additionally, we report for the first time that acute application of isoflurane reduces IHC calcium currents, which may have implications for noise-induced IHC synaptic loss.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1523978"},"PeriodicalIF":4.2,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003290","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":"Advances in physiological and clinical relevance of hiPSC-derived brain models for precision medicine pipelines.","authors":"Negin Imani Farahani, Lisa Lin, Shama Nazir, Alireza Naderi, Leanne Rokos, Anthony Randal McIntosh, Lisa M Julian","doi":"10.3389/fncel.2024.1478572","DOIUrl":"10.3389/fncel.2024.1478572","url":null,"abstract":"<p><p>Precision, or personalized, medicine aims to stratify patients based on variable pathogenic signatures to optimize the effectiveness of disease prevention and treatment. This approach is favorable in the context of brain disorders, which are often heterogeneous in their pathophysiological features, patterns of disease progression and treatment response, resulting in limited therapeutic standard-of-care. Here we highlight the transformative role that human induced pluripotent stem cell (hiPSC)-derived neural models are poised to play in advancing precision medicine for brain disorders, particularly emerging innovations that improve the relevance of hiPSC models to human physiology. hiPSCs derived from accessible patient somatic cells can produce various neural cell types and tissues; current efforts to increase the complexity of these models, incorporating region-specific neural tissues and non-neural cell types of the brain microenvironment, are providing increasingly relevant insights into human-specific neurobiology. Continued advances in tissue engineering combined with innovations in genomics, high-throughput screening and imaging strengthen the physiological relevance of hiPSC models and thus their ability to uncover disease mechanisms, therapeutic vulnerabilities, and tissue and fluid-based biomarkers that will have real impact on neurological disease treatment. True physiological understanding, however, necessitates integration of hiPSC-neural models with patient biophysical data, including quantitative neuroimaging representations. We discuss recent innovations in cellular neuroscience that can provide these direct connections through generative AI modeling. Our focus is to highlight the great potential of synergy between these emerging innovations to pave the way for personalized medicine becoming a viable option for patients suffering from neuropathologies, particularly rare epileptic and neurodegenerative disorders.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1478572"},"PeriodicalIF":4.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003199","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":"Iconography of abnormal non-neuronal cells in pediatric focal cortical dysplasia type IIb and tuberous sclerosis complex.","authors":"Joyce Zhang, Deneen Argueta, Xiaoping Tong, Harry V Vinters, Gary W Mathern, Carlos Cepeda","doi":"10.3389/fncel.2024.1486315","DOIUrl":"10.3389/fncel.2024.1486315","url":null,"abstract":"<p><p>Once believed to be the culprits of epileptogenic activity, the functional properties of balloon/giant cells (BC/GC), commonly found in some malformations of cortical development including focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC), are beginning to be unraveled. These abnormal cells emerge during early brain development as a result of a hyperactive mTOR pathway and may express both neuronal and glial markers. A paradigm shift occurred when our group demonstrated that BC/GC in pediatric cases of FCDIIb and TSC are unable to generate action potentials and lack synaptic inputs. Hence, their role in epileptogenesis remained obscure. In this review, we provide a detailed characterization of abnormal non-neuronal cells including BC/GC, intermediate cells, and dysmorphic/reactive astrocytes found in FCDIIb and TSC cases, with special emphasis on electrophysiological and morphological assessments. Regardless of pathology, the electrophysiological properties of abnormal cells appear more glial-like, while others appear more neuronal-like. Their morphology also differs in terms of somatic size, shape, and dendritic elaboration. A common feature of these types of non-neuronal cells is their inability to generate action potentials. Thus, despite their distinct properties and etiologies, they share a common functional feature. We hypothesize that, although the exact role of abnormal non-neuronal cells in FCDIIb and TSC remains mysterious, it can be suggested that cells displaying more glial-like properties function in a similar way as astrocytes do, i.e., to buffer K⁺ ions and neurotransmitters, while those with more neuronal properties, may represent a metabolic burden due to high energy demands but inability to receive or transmit electric signals. In addition, due to the heterogeneity of these cells, a new classification scheme based on morphological, electrophysiological, and gene/protein expression in FCDIIb and TSC cases seems warranted.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1486315"},"PeriodicalIF":4.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003271","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":"Astrocytes phenomics as new druggable targets in healthy aging and Alzheimer's disease progression.","authors":"Daniele Lana, Filippo Ugolini, Ludovica Iovino, Selene Attorre, Maria Grazia Giovannini","doi":"10.3389/fncel.2024.1512985","DOIUrl":"10.3389/fncel.2024.1512985","url":null,"abstract":"<p><p>For over a century after their discovery astrocytes were regarded merely as cells located among other brain cells to hold and give support to neurons. Astrocytes activation, \"astrocytosis\" or A1 functional state, was considered a detrimental mechanism against neuronal survival. Recently, the scientific view on astrocytes has changed. Accumulating evidence indicate that astrocytes are not homogeneous, but rather encompass heterogeneous subpopulations of cells that differ from each other in terms of transcriptomics, molecular signature, function and response in physiological and pathological conditions. In this review, we report and discuss the recent literature on the phenomic differences of astrocytes in health and their modifications in disease conditions, focusing mainly on the hippocampus, a region involved in learning and memory encoding, in the age-related memory impairments, and in Alzheimer's disease (AD) dementia. The morphological and functional heterogeneity of astrocytes in different brain regions may be related to their different housekeeping functions. Astrocytes that express diverse transcriptomics and phenomics are present in strictly correlated brain regions and they are likely responsible for interactions essential for the formation of the specialized neural circuits that drive complex behaviors. In the contiguous and interconnected hippocampal areas CA1 and CA3, astrocytes show different, finely regulated, and region-specific heterogeneity. Heterogeneous astrocytes have specific activities in the healthy brain, and respond differently to physiological or pathological stimuli, such as inflammaging present in normal brain aging or beta-amyloid-dependent neuroinflammation typical of AD. To become reactive, astrocytes undergo transcriptional, functional, and morphological changes that transform them into cells with different properties and functions. Alterations of astrocytes affect the neurovascular unit, the blood-brain barrier and reverberate to other brain cell populations, favoring or dysregulating their activities. It will be of great interest to understand whether the differential phenomics of astrocytes in health and disease can explain the diverse vulnerability of the hippocampal areas to aging or to different damaging insults, in order to find new astrocyte-targeted therapies that might prevent or treat neurodegenerative disorders.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1512985"},"PeriodicalIF":4.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003233","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":"Nerve repair with polylactic acid and inosine treatment enhance regeneration and improve functional recovery after sciatic nerve transection.","authors":"Fellipe Soares Dos Santos Cardoso, Guilherme Dos Santos Maria, Fernanda Marques Pestana, Ricardo Cardoso, Bruna Dos Santos Ramalho, Luiza Dos Santos Heringer, Tiago Bastos Taboada, Ana Maria Blanco Martinez, Fernanda Martins de Almeida","doi":"10.3389/fncel.2024.1525024","DOIUrl":"10.3389/fncel.2024.1525024","url":null,"abstract":"<p><strong>Background: </strong>Following transection, nerve repair using the polylactic acid (PLA) conduit is an effective option. In addition, inosine treatment has shown potential to promote nerve regeneration. Therefore, this study aimed to investigate the regenerative potential of inosine after nerve transection and polylactic acid conduit repair.</p><p><strong>Methods: </strong>C57/Black6 mice were subjected to sciatic nerve transection, repair with PLA conduit, and intraperitoneal injection of saline or inosine 1 h after injury and daily for 1 week. To assess motor and sensory recovery, functional tests were performed before and weekly up to 8 weeks after injury. Following, to evaluate the promotion of regeneration and myelination, electroneuromyography, morphometric analysis and immunohistochemistry were then performed.</p><p><strong>Results: </strong>Our results showed that the inosine group had a greater number of myelinated nerve fibers (1,293 ± 85.49 vs. 817 ± 89.2), an increase in neurofilament high chain (NFH) and myelin basic protein (MBP) immunolabeling and a greater number of fibers within the ideal g-ratio (453.8 ± 45.24 vs. 336.6 ± 37.01). In addition, the inosine group presented a greater adenosine A2 receptor (A2AR) immunolabeling area. This resulted in greater compound muscle action potential amplitude and nerve conduction velocity, leading to preservation of muscle and neuromuscular junction integrity, and consequently, the recovery of motor and sensory function.</p><p><strong>Conclusion: </strong>Our findings suggest that inosine may enhance regeneration and improve both motor and sensory function recovery after nerve transection when repaired with a poly-lactic acid conduit. This advances the understanding of biomaterials and molecular treatments.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1525024"},"PeriodicalIF":4.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003287","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":"Obstructive sleep apnoea as a neuromuscular respiratory disease arising from an excess of central GABAergic neurotransmitters: a new disease model.","authors":"Domenico Maurizio Toraldo, Alessandra Palma Modoni, Egeria Scoditti, Francesco De Nuccio","doi":"10.3389/fncel.2024.1429570","DOIUrl":"https://doi.org/10.3389/fncel.2024.1429570","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1429570"},"PeriodicalIF":4.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003296","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":"Evolutionary origins of synchronization for integrating information in neurons.","authors":"Takashi Shibata, Noriaki Hattori, Hisao Nishijo, Tsutomu Takahashi, Yuko Higuchi, Satoshi Kuroda, Kaoru Takakusaki","doi":"10.3389/fncel.2024.1525816","DOIUrl":"10.3389/fncel.2024.1525816","url":null,"abstract":"<p><p>The evolution of brain-expressed genes is notably slower than that of genes expressed in other tissues, a phenomenon likely due to high-level functional constraints. One such constraint might be the integration of information by neuron assemblies, enhancing environmental adaptability. This study explores the physiological mechanisms of information integration in neurons through three types of synchronization: chemical, electromagnetic, and quantum. Chemical synchronization involves the diffuse release of neurotransmitters like dopamine and acetylcholine, causing transmission delays of several milliseconds. Electromagnetic synchronization encompasses action potentials, electrical gap junctions, and ephaptic coupling. Electrical gap junctions enable rapid synchronization within cortical GABAergic networks, while ephaptic coupling allows structures like axon bundles to synchronize through extracellular electromagnetic fields, surpassing the speed of chemical processes. Quantum synchronization is hypothesized to involve ion coherence during ion channel passage and the entanglement of photons within the myelin sheath. Unlike the finite-time synchronization seen in chemical and electromagnetic processes, quantum entanglement provides instantaneous non-local coherence states. Neurons might have evolved from slower chemical diffusion to rapid temporal synchronization, with ion passage through gap junctions within cortical GABAergic networks potentially facilitating both fast gamma band synchronization and quantum coherence. This mini-review compiles literature on these three synchronization types, offering new insights into the physiological mechanisms that address the binding problem in neuron assemblies.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1525816"},"PeriodicalIF":4.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003269","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":"Self-reported health, persistent symptoms, and daily activities 2 years after hospitalization for COVID-19.","authors":"Roda Alhasan, Lena Rafsten, Alexandra C Larsson, Katharina S Sunnerhagen, Hanna C Persson","doi":"10.3389/fncel.2024.1460119","DOIUrl":"10.3389/fncel.2024.1460119","url":null,"abstract":"<p><strong>Introduction: </strong>Since the onset of the COVID-19 pandemic, 775 million cases have been reported globally. While many individuals recover fully, a significant proportion develop persistent symptoms. Numerous studies have investigated the long-term symptoms of COVID-19; however, the full extent and impact of these symptoms remain inadequately understood. The aim of this study was to investigate the prevalence of self-reported persistent symptoms, focusing on respiratory symptoms and fatigue and the impact on functional status 2 years after hospitalization for COVID-19.</p><p><strong>Methods: </strong>This study is prospective and includes participants from a longitudinal multi-center cohort that follows patients previously hospitalized due to COVID-19 (<i>n</i> = 211). The current study encompasses the 2-year follow-up, using post-hospitalization questionnaire surveys. Analyzed data were collected before discharge and at the 2-year follow-up. Participants were grouped by age, sex and COVID-19 severity and group comparisons where conducted. Logistic regression analysis was used to study functional impairment.</p><p><strong>Results: </strong>Two years after hospital discharge due to COVID-19, 125 participants completed the 2-year follow-up. The mean age of participants was 66 years (SD 12.2), and 68% were male. The majority of participants reported present respiratory symptoms (<i>n</i> = 83, 69%) and fatigue (<i>n</i> = 98, 78%) at the 2-year follow-up. Persistent respiratory symptoms and fatigue impacted functional status substantially (<i>p</i> = <0.001, <i>p</i> = 0.028, respectively). No significant differences were observed among groups depending on age, sex, or severity of COVID-19.</p><p><strong>Conclusion: </strong>For some individuals regardless of age, sex or COVID-19 severity, respiratory symptoms and fatigue may persist for up to 2 years following COVID-19. Hence, having available support from professionals knowledgeable about COVID-19 is imperative. Further research is important to unravel the mechanisms of long-term symptoms following COVID-19 and to develop effective therapeutic and rehabilitative interventions.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1460119"},"PeriodicalIF":4.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003305","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":"Role of insulin-like growth factor-2 in Alzheimer's disease induced memory impairment and underlying mechanisms.","authors":"Ruiqi Chen, Xing Lu, Anqi Xiao, Junpeng Ma","doi":"10.3389/fncel.2024.1520253","DOIUrl":"10.3389/fncel.2024.1520253","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most prevalent type of dementia. Treatments for AD do not reverse the loss of brain function; rather, they decrease the rate of cognitive deterioration. Current treatments are ineffective in part because they do not address neurotrophic mechanisms, which are believed to be critical for functional recovery. Given that structural losses are assumed to be the root cause of cognitive impairment in AD, strengthening neurotrophic pathways may be a useful preventative therapeutic approach. Insulin-like growth factor-2 (IGF2), which is widely expressed in the central nervous system (CNS), has emerged as a crucial mechanism of synaptic plasticity and learning and memory, and many studies have indicated that this neurotrophic peptide is a viable candidate for treating and preventing AD-induced cognitive decline. An increase in IGF2 levels improves memory in healthy animals and alleviates several symptoms associated with neurodegenerative disorders. These effects are primarily caused by the IGF2 receptor, which is widely expressed in neurons and controls protein trafficking, synthesis, and degradation. However, the use of IGF2 as a potential target for the development of novel pharmaceuticals to treat AD-induced memory impairment needs further investigation. We compiled recent studies on the role of IGF2 in AD-associated memory issues and summarized the current knowledge regarding IGF2 expression and function in the brain, specifically in AD-induced memory impairment.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1520253"},"PeriodicalIF":4.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003299","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}