World Journal of Pediatrics, Journal Year: 2023, Volume and Issue: 20(1), P. 40 - 53
Published: Oct. 25, 2023
Language: Английский
Nature, Journal Year: 2023, Volume and Issue: 622(7981), P. 120 - 129
Published: Sept. 6, 2023
Abstract Multimodal astrocyte–neuron communications govern brain circuitry assembly and function 1 . For example, through rapid glutamate release, astrocytes can control excitability, plasticity synchronous activity 2,3 of synaptic networks, while also contributing to their dysregulation in neuropsychiatric conditions 4–7 communicate fast focal they should possess an apparatus for Ca 2+ -dependent exocytosis similar neurons 8–10 However, the existence this mechanism has been questioned 11–13 owing inconsistent data 14–17 a lack direct supporting evidence. Here we revisited astrocyte hypothesis by considering emerging molecular heterogeneity 18–21 using molecular, bioinformatic imaging approaches, together with cell-specific genetic tools that interfere vivo. By analysing existing single-cell RNA-sequencing databases our patch-seq data, identified nine molecularly distinct clusters hippocampal astrocytes, among which found notable subpopulation selectively expressed synaptic-like glutamate-release machinery localized discrete sites. Using GluSnFR-based 22 situ vivo, corresponding subgroup responds reliably astrocyte-selective stimulations subsecond release events at spatially precise hotspots, were suppressed astrocyte-targeted deletion vesicular transporter (VGLUT1). Furthermore, or its isoform VGLUT2 revealed specific contributions glutamatergic cortico-hippocampal nigrostriatal circuits during normal behaviour pathological processes. uncovering atypical specialized adult brain, provide insights into complex roles central nervous system (CNS) physiology diseases, identify potential therapeutic target.
Language: Английский
Citations
149
The Lancet Neurology, Journal Year: 2023, Volume and Issue: 22(8), P. 723 - 734
Published: June 20, 2023
Language: Английский
Citations
103
Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 178, P. 106027 - 106027
Published: Feb. 2, 2023
A large set of inflammatory molecules and their receptors are induced in epileptogenic foci patients with pharmacoresistant epilepsies structural etiologies or refractory status epilepticus. Studies animal models mimicking these clinical conditions have shown that the activation specific signallings forebrain neurons glial cells may modify seizure thresholds, thus contributing to both ictogenesis epileptogenesis. The search for mechanisms underlying effects has highlighted mediators CNS-specific neuromodulatory functions, addition canonical immune responses pathogen recognition clearance. This review reports how they contribute alter inhibitory/excitatory balance neural networks underlie seizures. In particular, we describe key findings related ictogenic role prototypical cytokines (IL-1β TNF) danger signals (HMGB1), modulatory neuronal excitability, effects. It will be discussed harnessing properties lead novel therapies control drug-resistant
Language: Английский
Citations
43
Advanced Materials, Journal Year: 2024, Volume and Issue: 36(26)
Published: April 7, 2024
Abstract Brain disorders represent a significant challenge in medical science due to the formidable blood–brain barrier (BBB), which severely limits penetration of conventional therapeutics, hindering effective treatment strategies. This review delves into innovative realm biomimetic nanodelivery systems, including stem cell‐derived nanoghosts, tumor cell membrane‐coated nanoparticles, and erythrocyte membrane‐based carriers, highlighting their potential circumvent BBB's restrictions. By mimicking native properties, these nanocarriers emerge as promising solution for enhancing drug delivery brain, offering strategic advantage overcoming barrier's selective permeability. The unique benefits leveraging membranes from various sources is evaluated advanced technologies fabricating membrane‐encapsulated nanoparticles capable masquerading endogenous cells are examined. enables targeted broad spectrum therapeutic agents, ranging small molecule drugs proteins, thereby providing an approach neurocare. Further, contrasts capabilities limitations with traditional methods, underlining enable targeted, sustained, minimally invasive modalities. concluded perspective on clinical translation underscoring transformative impact landscape intractable brain diseases.
Language: Английский
Citations
30
Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(5), P. 334 - 350
Published: March 26, 2024
Language: Английский
Citations
28
Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 179, P. 106058 - 106058
Published: March 1, 2023
The epilepsies are a diverse spectrum of disease states characterized by spontaneous seizures and associated comorbidities. Neuron-focused perspectives have yielded an array widely used anti-seizure medications able to explain some, but not all, the imbalance excitation inhibition which manifests itself as seizures. Furthermore, rate pharmacoresistant epilepsy remains high despite regular approval novel medications. Gaining more complete understanding processes that turn healthy brain into epileptic (epileptogenesis) well generate individual (ictogenesis) may necessitate broadening our focus other cell types. As will be detailed in this review, astrocytes augment neuronal activity at level neurons form gliotransmission tripartite synapse. Under normal conditions, essential maintenance blood-brain barrier integrity remediation inflammation oxidative stress, these functions impaired. Epilepsy results disruptions way relate each gap junctions has important implications for ion water homeostasis. In their activated state, contribute imbalances excitability due decreased capacity take up metabolize glutamate increased adenosine. adenosine metabolism, DNA hypermethylation epigenetic changes underly epileptogenesis. Lastly, we explore potential explanatory power astrocyte function detail specific context comorbid occurrence Alzheimer's disruption sleep-wake regulation with both conditions.
Language: Английский
Citations
39
Chemosphere, Journal Year: 2023, Volume and Issue: 324, P. 138251 - 138251
Published: March 4, 2023
Language: Английский
Citations
35
Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16
Published: July 31, 2023
Astrocytes are specialized non-neuronal glial cells of the central nervous system, contributing to neuronal excitability and synaptic transmission (gliotransmission). play a key roles in epileptogenesis seizure generation. Epilepsy, as chronic disorder characterized by hyperexcitation hypersynchronization, is accompanied substantial disturbances impairment astrocytic functions signaling. Anti-seizure drugs that provide symptomatic control seizures primarily target neural activity. In epileptic patients with inadequate available anti-seizure drugs, novel therapeutic candidates needed. These should treat epilepsy anti-epileptogenic disease-modifying effects. Evidence from human animal studies shows astrocytes have value for developing new drugs. this review, we present hyperexcitability activity following an etiology-based approach. We analyze role both development (epileptogenesis) generation (ictogenesis). Several promising strategies attempted modify astroglial treating being developed: (1) selective targeting glia-related molecular mechanisms glutamate transport; (2) modulation tonic GABA release astrocytes; (3) gliotransmission; (4) Kir4.1-BDNF system; (5) Na+/K+/ATPase activity; (6) DNA hypo- or hypermethylation candidate genes (7) gap junction regulators; (8) adenosine kinase (the major adenosine-metabolizing enzyme); (9) microglia-astrocyte communication inflammatory pathways. Novel now been developed, such astroglia-targeted gene therapy broad spectrum genetic constructs cells.
Language: Английский
Citations
29
Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 179, P. 106054 - 106054
Published: Feb. 25, 2023
Nervous system is segregated from the body by complex of barriers. The CNS protected (i) blood–brain and blood-spinal cord barrier between intracerebral intraspinal blood vessels brain parenchyma; (ii) arachnoid blood-cerebrospinal fluid barrier; (iii) circumventricular organs made tanycytes (iv) choroid plexus blood-CSF formed ependymocytes. In peripheral nervous nerve-blood secured tight junctions specialised glial cells known as perineural cells. astroglia contribute to all barriers through glia limitans, which represent parenchymal portion system. Astroglia secretion various paracrine factors regulate permeability endothelial vascular in pathology damage or asthenia astrocytes may compromise integrity.
Language: Английский
Citations
28
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4161 - 4161
Published: April 9, 2024
Neuroinflammation and epilepsy are different pathologies, but, in some cases, they so closely related that the activation of one pathologies leads to development other. In this work, we discuss three main cell types involved neuroinflammation, namely (i) reactive astrocytes, (ii) activated microglia, infiltration (iii) peripheral immune cells central nervous system. Then, how neuroinflammation interconnected describe use repurposing drugs with anti-inflammatory properties have been shown a beneficial effect models. This review reinforces idea compounds designed alleviate seizures need target not only caused by astrocytes microglia but also interaction these infiltrated cells.
Language: Английский
Citations
15