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001-es BibID:	BIBFORM122718
035-os BibID:	(Scopus)85193926706 (WOS)001229202800001
Első szerző:	Dócs Klaudia (orvos)
Cím:	Reactive spinal glia convert 2-AG to prostaglandins to drive aberrant astroglial calcium signaling / Klaudia Dócs, Anita Balázs, Ildikó Papp, Peter Szücs, Zoltán Hegyi
Dátum:	2024
ISSN:	1662-5102
Megjegyzések:	The endogenous cannabinoid 2-arachidonoylglycerol (2-AG) influences neurotransmission in the central nervous system mainly by activating type 1 cannabinoid receptor (CB1). Following its release, 2-AG is broken down by hydrolases to yield arachidonic acid, which may subsequently be metabolized by cyclooxygenase-2 (COX-2). COX-2 converts arachidonic acid and also 2-AG into prostanoids, well-known inflammatory and pro-nociceptive mediators. Here, using immunohistochemical and biochemical methods and pharmacological manipulations, we found that reactive spinal astrocytes and microglia increase the expression of COX-2 and the production of prostaglandin E2 when exposed to 2-AG. Both 2-AG and PGE2 evoke calcium transients in spinal astrocytes, but PGE2 showed 30% more efficacy and 55 times more potency than 2-AG. Unstimulated spinal dorsal horn astrocytes responded to 2-AG with calcium transients mainly through the activation of CB1. 2-AG induced exaggerated calcium transients in reactive astrocytes, but this increase in the frequency and area under the curve of calcium signals was only partially dependent on CB1. Instead, aberrant calcium transients were almost completely abolished by COX-2 inhibition. Our results suggest that both reactive spinal astrocytes and microglia perform an endocannabinoid-prostanoid switch to produce PGE2 at the expense of 2-AG. PGE2 in turn is responsible for the induction of aberrant astroglial calcium signals which, together with PGE2 production may play role in the development and maintenance of spinal neuroinflammation-associated disturbances such as central sensitization.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk 2-AG astrocyte calcium signaling cannabinoid CB1 COX-2 prostaglandin reactive astrocyte
Megjelenés:	Frontiers in Cellular Neuroscience. - 18 (2024), p. 1-17. -
További szerzők:	Balázs Anita (1984-) (molekuláris biológus) Papp Ildikó (1976-) (biológus) Szűcs Péter (1974-) (kutatóorvos) Hegyi Zoltán (1983-) (molekuláris biológus)
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM069841
Első szerző:	Holló Krisztina (vegyész)
Cím:	Interleukin-1 receptor type 1 is over-expressed in neurons but not in glial cells within the rat superficial spinal dorsal horn in complete Freund adjuvant induced inflammatory pain / Krisztina Holló, László Ducza, Zoltán Hegyi, Klaudia Dócs, Krisztina Hegedűs, Erzsébet Bakk, Ildikó Papp, Gréta Kis, Zoltán Mészár, Zsuzsanna Bardóczi, Miklós Antal
Dátum:	2017
Megjegyzések:	AbstractBackground: All known biological functions of the pro-inflammatory cytokine interleukin-1? (IL-1?) are mediatedby type 1 interleukin receptor (IL-1R1). IL-1??IL-1R1 signaling modulates various neuronal functions including spinalpain processing. Although the role of IL-1? in pain processing is generally accepted, there is a discussion in the literaturewhether IL-1? exerts its effect on spinal pain processing by activating neuronal or glial IL-1R1. To contributeto this debate, here we investigated the expression and cellular distribution of IL-1R1 in the superficial spinaldorsal horn in control animals and also in inflammatory pain.Methods: Experiments were performed on rats and wild type as well as IL-1R1-deficient mice. Inflammatorypain was evoked by unilateral intraplantar injection of complete Freund adjuvant (CFA). The nociceptiveresponsiveness of control and CFA-treated animals were tested daily for withdrawal responses to mechanicaland thermal stimuli before and after CFA injection. Changes in the expression of 48 selected genes/mRNAsand in the quantity of IL-1R1 protein during the first 3 days after CFA injection were measured with theTaqMan low-density array method and Western blot analysis, respectively. The cellular localization of IL-1R1protein was investigated with single and double staining immunocytochemical methods.Results: We found a six times and two times increase in IL-1R1 mRNA and protein levels, respectively, in thedorsal horn of CFA-injected animals 3 days after CFA injection, at the time of the summit of mechanical andthermal allodynia. Studying the cellular distribution of IL-1R1, we found an abundant expression of IL-1R1 onthe somatodendritic compartment of neurons and an enrichment of the receptor in the postsynaptic membranes ofsome excitatory synapses. In contrast to the robust neuronal localization, we observed only a moderate expression ofIL-1R1 on astrocytes and a negligible one on microglial cells. CFA injection into the hind paw caused a remarkableincrease in the expression of IL-1R1 in neurons, but did not alter the glial expression of the receptor.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban IL-1R1 Rodents Inflammatory pain evoked by CFA injection Immunohistochemistry Superficial spinal dorsal horn
Megjelenés:	Journal of Neuroinflammation. - 14 : 1 (2017), p. 1-18. -
További szerzők:	Ducza László (1987-) (molekuláris biológus) Hegyi Zoltán (1983-) (molekuláris biológus) Dócs Klaudia (1989-) (orvos) Hegedűs Krisztina Bakk Erzsébet Papp Ildikó (1976-) (biológus) Kis Gréta (1979-) (környezetkutató) Mészár Zoltán Mihály (1977-) (agrármérnök, biotechnológus) Bardóczi Zsuzsanna Antal Miklós (1951-) (orvos, anatómus)
Pályázati támogatás:	KTIA_NAP_13-1-2013-0001 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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