Representation and control of pain and itch by distinct prefrontal neural ensembles

Neuron, Год журнала: 2023, Номер 111(15), С. 2414 - 2431.e7

Опубликована: Май 23, 2023

Язык: Английский

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Construction of functional neural network tissue combining CBD-NT3-modified linear-ordered collagen scaffold and TrkC-modified iPSC-derived neural stem cells for spinal cord injury repair

Bioactive Materials, Год журнала: 2024, Номер 35, С. 242 - 258

Опубликована: Фев. 3, 2024

Induced pluripotent stem cells (iPSCs) can be personalized and differentiated into neural (NSCs), thereby effectively providing a source of transplanted for spinal cord injury (SCI). To further improve the repair efficiency SCI, we designed functional network tissue based on TrkC-modified iPSC-derived NSCs CBD-NT3-modified linear-ordered collagen scaffold (LOCS). We confirmed that transplantation this regenerated neurons synapses, improved microenvironment injured area, enhanced remodeling extracellular matrix, promoted recovery hind limbs in rat SCI model with complete transection. RNA sequencing metabolomic analyses also effect from multiple perspectives revealed its potential mechanism treating SCI. Together, constructed using human iPSCs-derived as seed interaction receptors ligands first time. This therapeutic thus confirming feasibility LOCS valuable direction research.

Язык: Английский

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Deep sequencing of Phox2a nuclei reveals five classes of anterolateral system neurons

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(23)

Опубликована: Май 28, 2024

The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies perception of pain, itch, skin temperature. Despite its importance, our understanding this has been hampered by considerable functional molecular diversity constituent cells. Here, we use fluorescence-activated cell sorting isolate ALS neurons belonging Phox2a-lineage for single-nucleus RNA sequencing. We reveal five distinct clusters (ALS1-5) document their laminar distribution in using situ hybridization. identify three located predominantly laminae I–III dorsal horn (ALS1-3) two with bodies deeper (ALS4 ALS5). Our findings transcriptional logic neuronal adult mouse uncover identity previously identified classes projection neurons. also show these signatures can be used target groups retrograde viral tracing. Overall, provide valuable resource studying somatosensory biology targeting subclasses

Язык: Английский

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The mechanisms of perineuronal net abnormalities in contributing aging and neurological diseases

Ageing Research Reviews, Год журнала: 2023, Номер 92, С. 102092 - 102092

Опубликована: Окт. 13, 2023

Язык: Английский

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Immunotherapies in chronic pain through modulation of neuroimmune interactions

Pharmacology & Therapeutics, Год журнала: 2023, Номер 248, С. 108476 - 108476

Опубликована: Июнь 10, 2023

Язык: Английский

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Roles of Thermosensitive Transient Receptor Channels TRPV1 and TRPM8 in Paclitaxel-Induced Peripheral Neuropathic Pain

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 5813 - 5813

Опубликована: Май 27, 2024

Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, nociceptor and heat sensor) melastatin 8 (TRPM8, cold in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, calcium imaging revealed that the expression functional activity TRPV1 were upregulated rat dorsal root ganglion (DRG) neurons PIPNP. Behavioral assessments using von Frey brush tests demonstrated mechanical hyperalgesia was significantly inhibited by intraperitoneal or intrathecal administration antagonist capsazepine, indicating played key role Conversely, TRPM8 protein decreased its reduced DRG neurons. Furthermore, activation via topical application menthol injection WS-12 attenuated pain. Mechanistically, triggered capsaicin (a agonist) after cultured neurons, especially paclitaxel-treated group. These findings showed upregulation inhibition are involved generation PIPNP, they suggested function might underlie analgesic effects menthol.

Язык: Английский

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Deficiency of KIF15 contributes to oxaliplatin-induced cold hypersensitivity by limiting Annexin A2 and enhancing TRPA1 localization in DRG neuronal membrane

Neuropharmacology, Год журнала: 2025, Номер 269, С. 110343 - 110343

Опубликована: Фев. 4, 2025

Язык: Английский

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Heterogeneity of Layer 1 Interneurons in the Mouse Medial Prefrontal Cortex

The Journal of Comparative Neurology, Год журнала: 2025, Номер 533(3)

Опубликована: Март 1, 2025

Cortical Layer 1 (L1) acts as a critical relay for processing long-range inputs. GABAergic inhibitory interneurons (INs) in this layer (Layer [L1INs]) function gates, regulating these inputs and modulating the activity of deeper cortical layers. However, their characteristics circuits medial prefrontal cortex (mPFC) remain poorly understood. Using biocytin labeling, we identified three distinct morphological types mPFC L1INs: neurogliaform cells (NGCs), elongated NGCs (eNGCs), single-bouquet cell-like (SBC-like) cells. Whole-cell recordings revealed firing patterns across subtypes: eNGCs predominantly exhibited late-spiking (LS) patterns, SBC-like displayed higher prevalence non-LS (NLS) patterns. We observed both electrical chemical connections among L1INs. Optogenetic activation NDNF+ L1INs demonstrated broad effects on neurons. The strength inhibition pyramidal neurons (PyNs) INs layer-specific preference. These findings highlight functional diversity suggest potential role supporting order cognitive functions.

Язык: Английский

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Descending locus coeruleus noradrenergic signaling to spinal astrocyte subset is required for stress-induced pain facilitation

Опубликована: Март 13, 2025

It is known that stress powerfully alters pain, but its underlying mechanisms remain elusive. Here, we identified a circuit, locus coeruleus descending noradrenergic neurons projecting to the spinal dorsal horn (LC →SDH -NA neurons), activated by acute exposure restraint and required for stress-induced mechanical pain hypersensitivity in mice. Interestingly, primary target of NA released from LC -NAergic terminals causing was α 1A -adrenaline receptors (α Rs) Hes5-positive (Hes5 + ) astrocytes located SDH, an astrocyte subset has ability induce sensitization. Furthermore, activation Hes5 reduced activity SDH-inhibitory (SDH-INs) have inhibitory role processing. This astrocytic reduction IN canceled A 1 -adenosine receptor (A R)-knockdown SDH-INs, R-knockdown suppressed caused stress. Therefore, our findings suggest neuronal signaling SDH subsequent SDH-IN are essential facilitation

Язык: Английский

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Descending locus coeruleus noradrenergic signaling to spinal astrocyte subset is required for stress-induced pain facilitation

Опубликована: Март 13, 2025

It is known that stress powerfully alters pain, but its underlying mechanisms remain elusive. Here, we identified a circuit, locus coeruleus descending noradrenergic neurons projecting to the spinal dorsal horn (LC →SDH -NA neurons), activated by acute exposure restraint and required for stress-induced mechanical pain hypersensitivity in mice. Interestingly, primary target of NA released from LC -NAergic terminals causing was α 1A -adrenaline receptors (α Rs) Hes5-positive (Hes5 + ) astrocytes located SDH, an astrocyte subset has ability induce sensitization. Furthermore, activation Hes5 reduced activity SDH-inhibitory (SDH-INs) have inhibitory role processing. This astrocytic reduction IN canceled A 1 -adenosine receptor (A R)-knockdown SDH-INs, R-knockdown suppressed caused stress. Therefore, our findings suggest neuronal signaling SDH subsequent SDH-IN are essential facilitation

Язык: Английский

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