npj Imaging, Journal Year: 2024, Volume and Issue: 2(1)
Published: Dec. 4, 2024
Language: Английский
Nature, Journal Year: 2024, Volume and Issue: 630(8017), P. 596 - 608
Published: June 19, 2024
Language: Английский
Citations
18
Journal of Biotechnology, Journal Year: 2024, Volume and Issue: 389, P. 1 - 12
Published: May 1, 2024
Aging is associated with the slowdown of neuronal processing and cognitive performance in brain; however, exact cellular mechanisms behind this deterioration humans are poorly elucidated. Recordings human acute brain slices prepared from tissue resected during surgery enable investigation changes age. Although neocortical fast-spiking cells widely implicated network activities underlying processes, they vulnerable to neurodegeneration. Herein, we analyzed electrical properties 147 interneurons neocortex samples 106 patients aged 11–84 years. By studying electrophysiological features action potentials passive membrane properties, report that potential overshoot significantly decreases spike half-width increases Moreover, maximum-rise speed (but not repolarization or afterhyperpolarization amplitude) changed age, suggesting a particular weakening sodium channel current generated soma. Cell measured as input resistance, time constant, cell capacitance remained unaffected by senescence. Thus, conclude shows significant This may contribute cortical functions aging.
Language: Английский
Citations
4
Neuron, Journal Year: 2024, Volume and Issue: 112(21), P. 3602 - 3617.e9
Published: Oct. 14, 2024
Human-specific (HS) genes have been implicated in brain evolution, but their impact on human neuron development and diseases remains unclear. Here, we study SRGAP2B/C, two HS gene duplications of the ancestral synaptic SRGAP2A, cortical pyramidal neurons (CPNs) xenotransplanted mouse cortex. Downregulation SRGAP2B/C CPNs led to strongly accelerated development, indicating requirement for neoteny that distinguishes synaptogenesis. promoted by reducing levels SRGAP2A,thereby increasing postsynaptic accumulation SYNGAP1 protein, encoded a major intellectual disability/autism spectrum disorder (ID/ASD) gene. Combinatorial loss-of-function experiments vivo revealed tempo synaptogenesis is set reciprocal antagonism between SRGAP2A SYNGAP1, which tipped toward SRGAP2B/C. Thus, can modify phenotypic expression genetic mutations leading ID/ASD through regulation neoteny.
Language: Английский
Citations
4
Neuron, Journal Year: 2025, Volume and Issue: 113(5), P. 649 - 669
Published: Feb. 12, 2025
The axon initial segment (AIS) is a highly specialized compartment in neurons that resides between axonal and somatodendritic domains. localization of the AIS proximal part essential for its two major functions: generating modulating action potentials maintaining neuron polarity. Recent findings revealed incredibly stable generated from dynamic components can undergo extensive structural functional changes response to alterations activity levels. These activity-dependent structure function have profound consequences neuronal functioning, plasticity has emerged as key regulator network homeostasis. This review highlights functions AIS, architecture, how organization remodeling are influenced by developmental both acute chronic adaptations. It also discusses mechanisms underlying these processes explores dysregulated may contribute brain disorders.
Language: Английский
Citations
0
Journal of Virology, Journal Year: 2025, Volume and Issue: unknown
Published: March 25, 2025
ABSTRACT Long noncoding RNAs (lncRNAs) are a newer class of transcripts identified as key regulators biological processes. Here, we aimed to identify novel lncRNA targets that play critical roles in major human respiratory viral infections by systematically mining large-scale transcriptomic data sets. Using bulk RNA-sequencing (RNA-seq) analysis, previously uncharacterized lncRNA, named virus-inducible modulator interferon response ( VILMIR ), was consistently upregulated after vitro influenza infection across multiple epithelial cell lines and A virus subtypes. also severe acute syndrome coronavirus 2 (SARS-CoV-2) syncytial (RSV) . We experimentally confirmed the interferon-beta (IFN-β) treatment A549 line found expression robustly induced IFN-β dose- time-specific manner. Single-cell RNA-seq analysis bronchoalveolar lavage fluid samples from disease 2019 (COVID-19) patients uncovered various types, including at least five immune cells. The upregulation cells further T monocyte lines, SUP-T1 THP-1, treatment. Finally, knockdown reduced magnitude host transcriptional responses both Together, our results show is interferon-stimulated gene (ISG) regulates may be potential therapeutic target for upon mechanistic investigation. IMPORTANCE Identifying factors regulate developing new therapeutics. Human long have been regulatory during processes; however, majority functions within antiviral remain unknown. In this study, influenza, 2, virus. demonstrated an several types. Our reveal present infections.
Language: Английский
Citations
0
The Journal of Physiology, Journal Year: 2024, Volume and Issue: 602(17), P. 4097 - 4110
Published: July 31, 2024
Abstract Since their discovery nearly 30 years ago, fibroblast growth factor homologous factors (FHFs) are now known to control the functionality of excitable tissues through a range mechanisms. Nervous and cardiac system dysfunctions caused by loss‐ or gain‐of‐function mutations in FHF genes. The best understood ‘canonical’ targets for action voltage‐gated sodium channels, recent studies have expanded repertoire ways that FHFs modulate channel gating. Additional ‘non‐canonical’ functions non‐excitable cells, including cancer been reported over past dozen years. This review summarizes evaluates canonical non‐canonical functions. image
Language: Английский
Citations
3
Trends in Genetics, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Citations
3
Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 92, P. 103033 - 103033
Published: May 6, 2025
The human brain has undergone remarkable structural and functional specializations compared to that of nonhuman primates (NHPs), underlying the advanced cognitive abilities unique humans. However, cellular genetic basis driving these remains largely unknown. Comparing humans our closest living relatives, chimpanzee other great apes, is essential for identifying truly human-specific features. Recent comparative studies with closely related NHPs at single-cell resolution using multimodal genomic profiling, assisted high-throughput screening have provided unprecedented insights into features their underpinnings. In this review, we synthesize current knowledge evolution molecular levels, emphasizing how changes shaped adaptations. We also discuss emerging opportunities presented by new technologies comprehensive atlases advancing understanding evolution.
Language: Английский
Citations
0
Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)
Published: May 9, 2025
Parkinson's disease (PD) is a complex neurological disorder characterized by the progressive degeneration of midbrain dopaminergic (mDA) neurons in substantia nigra (SN). This disrupts basal ganglia loops, leading to both motor and non-motor dysfunctions. Cell therapy for PD aims replace lost mDA restore DA neurotransmission denervated forebrain targets. In clinical trials PD, are implanted into target area, striatum, not SN where they normally located. ectopic localisation cells may affect functionality transplanted due absence appropriate host afferent regulation. We recently demonstrated that human induced pluripotent stem (hiPSCs) derived progenitors grafted pars compacta (SNpc) mouse model differentiated mature neurons, restored degenerated nigrostriatal pathway, recovery. The objective present study was evaluate long-term these intranigral-grafted assessing their electrophysiological properties. performed intranigral transplantation hiPSC-derived 6-hydroxydopamine RAG2-KO PD. recorded vivo unit extracellular activity anesthetised mice from 9 12 months post-transplantation. Their properties, including firing rates, patterns spike characteristics, were analysed compared with those native nigral control mice. exhibited functional characteristics similar such as large bi- or triphasic waveforms, low pacemaker-like two single-spike patterns. Although also displayed discharge frequencies below 10 Hz, mean frequency significantly lower than differential pattern distribution. Our findings indicate exhibit dopaminergic-like intrinsic membrane potential oscillations regular Additionally, irregular burst patterns, suggesting receive modulatory inputs. However, distinct potentially related origin incomplete maturation one year after transplantation.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: June 29, 2024
Microglia play key roles in shaping synaptic connectivity during neural circuits development. Whether microglia display human-specific features of structural and functional maturation is currently unknown. We show that the ancestral gene
Language: Английский
Citations
2