Osteosarcoma-Induced Pain Is Mediated by Glial Cell Activation in the Spinal Dorsal Horn, but Not Capsaicin-Sensitive Nociceptive Neurons: A Complex Functional and Morphological Characterization in Mice DOI Open Access

Noémi Bencze,

Bálint Scheich, Éva Szőke

и другие.

Cancers, Год журнала: 2024, Номер 16(10), С. 1788 - 1788

Опубликована: Май 7, 2024

Bone cancer and its related chronic pain are huge clinical problems since the available drugs often ineffective or cannot be used long term due to a broad range of side effects. The mechanisms, mediators targets need identified determine potential novel therapies. Here, we characterize mouse bone model induced by intratibial injection K7M2 osteosarcoma cells using an integrative approach investigate role capsaicin-sensitive peptidergic sensory nerves. mechanical threshold was assessed dynamic plantar aesthesiometry, limb loading weight bearing, spontaneous pain-related behaviors via observation, knee diameter with digital caliper, structural changes micro-CT glia cell activation immunohistochemistry in BALB/c mice both sexes. Capsaicin-sensitive neurons were defunctionalized systemic pretreatment high dose transient receptor vanilloid 1 (TRPV1) agonist resiniferatoxin (RTX). During 14- 28-day experiments, bearing on affected paw mechanonociceptive thresholds significantly decreased, demonstrating secondary hyperalgesia. Signs osteoplastic remodeling detected male female without any sex differences. Microglia shown increased ionized calcium-binding adapter molecule (Iba1) immunopositivity day 14 astrocyte enhanced glial fibrillary acidic protein (GFAP)-positive density 28 ipsilateral spinal dorsal horn. Interestingly, defunctionalization afferents representing approximately 2/3 nociceptive fibers did not alter functional parameters. provide first complex morphological characterization model. Bone-cancer-related hyperalgesia likely mediated central sensitization involving neuroinflammation horn, but neuronal system.

Язык: Английский

Calcium (Ca2+) hemostasis, mitochondria, autophagy, and mitophagy contribute to Alzheimer's disease as early moderators DOI
Fatemeh Hadi,

Mahsa Mortaja,

Zahra Hadi

и другие.

Cell Biochemistry and Function, Год журнала: 2024, Номер 42(5)

Опубликована: Июль 1, 2024

Abstract This review rigorously investigates the early cerebral changes associated with Alzheimer's disease, which manifest long before clinical symptoms arise. It presents evidence that dysregulation of calcium (Ca 2+ ) homeostasis, along mitochondrial dysfunction and aberrant autophagic processes, may drive disease's progression during its asymptomatic, preclinical stage. Understanding intricate molecular interplay unfolds this critical period offers a window into identifying novel therapeutic targets, thereby advancing treatment neurodegenerative disorders. The delves both established emerging insights alterations precipitated by disruption Ca balance, setting stage for cognitive decline neurodegeneration.

Язык: Английский

Процитировано

9
Characterisation of GFAP-Expressing Glial Cells in the Dorsal Root Ganglion after Spared Nerve Injury DOI Open Access
Elena A. Konnova, Alexandru‐Florian Deftu, Paul Chu Sin Chung

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(21), С. 15559 - 15559

Опубликована: Окт. 25, 2023

Satellite glial cells (SGCs), enveloping primary sensory neurons' somas in the dorsal root ganglion (DRG), contribute to neuropathic pain upon nerve injury. Glial fibrillary acidic protein (GFAP) serves as an SGC activation marker, though its DRG satellite cell specificity is debated. We employed hGFAP-CFP transgenic mouse line, designed for astrocyte studies, explore expression within peripheral nervous system (PNS) after spared injury (SNI). used diverse immunostaining techniques, Western blot analysis, and electrophysiology evaluate GFAP+ changes. Post-SNI, numbers increased without proliferation, were found near injured ATF3+ neurons. FABP7+ SGCs increased, yet 75.5% of lacked FABP7 expression. This suggests a significant subset are non-myelinating Schwann (nmSC), indicated by their presence but not ventral which lacks unmyelinated fibres. Additionally, patch clamp recordings from FABP7-cells SGC-specific Kir4.1 currents, instead displaying outward Kv currents expressing Kv1.1 Kv1.6 channels specific nmSCs. In conclusion, this study demonstrates GFAP two subpopulations post-SNI: FABP7- nmSCs, shedding light on GFAP's marker SNI.

Язык: Английский

Процитировано

15
Distinctive glial cells in the dorsal root ganglion: their morphology and functions DOI
Taro Koike

Anatomical Science International, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

Язык: Английский

Процитировано

0
The Role of Complexity Theory in Understanding Brain's Neuron–Glia Interactions DOI Creative Commons

Mariagiovanna Di Chiano,

Paolo Milior,

Yiannis Poulot-Becq-Giraudon

и другие.

European Journal of Neuroscience, Год журнала: 2025, Номер 61(5)

Опубликована: Март 1, 2025

ABSTRACT Brain information processing complexity is conventionally recognized as derived from neuronal activity, with neurons and their dynamic signalling responsible for the transfer of information. However, brain also contains other non‐neuronal cells, glial which exceed number are involved in processes related coding by neural networks underlying functions. Decisive advances characterization molecular physiological properties cells shed light on active roles neurotransmission physiopathology. This expanded relationship between glia challenges traditional neurobiology highlighting reciprocal influence, where it difficult to determine whether or initiate drive interactions. interplay creates a dilemma, causal hierarchy these two cell types remains unresolved. A philosophical tool, ‘Theory Complexity’ Edgard Morin can help better explain study neuron–glia Morin's proposal useful transform knowledge, order review functions antireductionist pattern. In this manuscript, we will discuss how use ‘retroactive loop’ principle at level, proposing new philosophical‐experimental grid that neuroscientists understanding glia–neuron interactions brain.

Язык: Английский

Процитировано

0
Role of TRPV1+ and TRPA1+ nociceptive neurons in delayed-onset muscle soreness: inhibition by hesperidin methyl chalcone DOI

G Cortez,

Mariana M. Bertozzi, Amanda M. Dionisio

и другие.

Inflammopharmacology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 26, 2025

Язык: Английский

Процитировано

0
Satellite Glial Cells Bridge Sensory Neuron Crosstalk in Visceral Pain and Cross-Organ Sensitization DOI Open Access
Li‐Ya Qiao

Journal of Pharmacology and Experimental Therapeutics, Год журнала: 2024, Номер 390(2), С. 213 - 221

Опубликована: Май 22, 2024

Following colonic inflammation, the uninjured bladder afferent neurons are also activated. The mechanisms and pathways underlying this sensory neuron cross-activation (from injured to neurons) not fully understood. Colonic reside in same spinal segments separated by satellite glial cells (SGCs) extracellular matrix dorsal root ganglia (DRG). SGCs communicate with a bidirectional fashion. This review summarizes differentially regulated genes/proteins DRG explores role of regulation crosstalk visceral cross-organ sensitization. highlights paracrine mediating neuron-SGC SGC-neuron coupling an emphasis on neurotrophins purinergic systems. Finally, I discuss results from recent RNAseq profiling reveal useful molecular markers for characterization, functional study, therapeutic targets SGCs. SIGNIFICANCE STATEMENT: Satellite largest subtypes play critical crosstalk, mechanism colon-bladder cross-sensitization. Identification novel unique can advance discovery treatment chronic pain including comorbidity.

Язык: Английский

Процитировано

2
Osteosarcoma-Induced Pain Is Mediated by Glial Cell Activation in the Spinal Dorsal Horn, but Not Capsaicin-Sensitive Nociceptive Neurons: A Complex Functional and Morphological Characterization in Mice DOI Open Access

Noémi Bencze,

Bálint Scheich, Éva Szőke

и другие.

Cancers, Год журнала: 2024, Номер 16(10), С. 1788 - 1788

Опубликована: Май 7, 2024

Bone cancer and its related chronic pain are huge clinical problems since the available drugs often ineffective or cannot be used long term due to a broad range of side effects. The mechanisms, mediators targets need identified determine potential novel therapies. Here, we characterize mouse bone model induced by intratibial injection K7M2 osteosarcoma cells using an integrative approach investigate role capsaicin-sensitive peptidergic sensory nerves. mechanical threshold was assessed dynamic plantar aesthesiometry, limb loading weight bearing, spontaneous pain-related behaviors via observation, knee diameter with digital caliper, structural changes micro-CT glia cell activation immunohistochemistry in BALB/c mice both sexes. Capsaicin-sensitive neurons were defunctionalized systemic pretreatment high dose transient receptor vanilloid 1 (TRPV1) agonist resiniferatoxin (RTX). During 14- 28-day experiments, bearing on affected paw mechanonociceptive thresholds significantly decreased, demonstrating secondary hyperalgesia. Signs osteoplastic remodeling detected male female without any sex differences. Microglia shown increased ionized calcium-binding adapter molecule (Iba1) immunopositivity day 14 astrocyte enhanced glial fibrillary acidic protein (GFAP)-positive density 28 ipsilateral spinal dorsal horn. Interestingly, defunctionalization afferents representing approximately 2/3 nociceptive fibers did not alter functional parameters. provide first complex morphological characterization model. Bone-cancer-related hyperalgesia likely mediated central sensitization involving neuroinflammation horn, but neuronal system.

Язык: Английский

Процитировано

0