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001-es BibID:	BIBFORM060025
Első szerző:	Kőszeghy Áron (Ph.D hallgató, élettanász)
Cím:	Endocannabinoid signaling modulates neurons of the pedunculopontine nucleus (PPN) via astrocytes. / Áron Kőszeghy, Adrienn Kovács, Tamás Bíró, Péter Szűcs, János Vincze, Zoltán Hegyi, Miklós Antal, Balázs Pál
Dátum:	2015
Megjegyzések:	The pedunculopontine nucleus (PPN) is known as the cholinergic part of the reticular activating system (RAS) and it plays an important role in transitions of slow-wave sleep to REM sleep and wakefulness. Although both exogenous and endocannabinoids affect sleep, the mechanism of endocannabinoid neuromodulation has not been characterized at cellular level in the PPN. In this paper, we demonstrate that both neurons and glial cells from the PPN respond to cannabinoid type 1 (CB1) receptor agonists. The neuronal response can be depolarization or hyperpolarization, while astrocytes exhibit more frequent calcium waves. All these effects are absent in CB1 gene-deficient mice. Blockade of the fast synaptic neurotransmission or neuronal action potential firing does not change the effect on the neuronal membrane potential significantly, while inhibition of astrocytic calcium waves by thapsigargin diminishes the response. Inhibition of group I metabotropic glutamate receptors (mGluRs) abolishes hyperpolarization, whereas blockade of group II mGluRs prevents depolarization. Initially active neurons and glial cells display weaker responses partially due to the increased endocannabinoid tone in their environment. Taken together, we propose that cannabinoid receptor stimulation modulates PPN neuronal activity in the following manner: active neurons may elicit calcium waves in astrocytes via endogenous CB1 receptor agonists. Astrocytes in turn release glutamate that activates different metabotropic glutamate receptors of neurons and modulate PPN neuronal activity.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Endocannabinoid Pedunculopontine nucleus CB1 receptor Neuromodulation Astrocyte Metabotropic glutamate receptor
Megjelenés:	Brain structure and function 220 : 5 (2015), p. 3023-3041. -
További szerzők:	Kovács Adrienn (1989-) (molekuláris biológus) Bíró Tamás (1968-) (élettanász) Szűcs Péter (1974-) (kutatóorvos) Vincze János (1988-) (orvos) Hegyi Zoltán (1983-) (molekuláris biológus) Antal Miklós (1951-) (orvos, anatómus) Pál Balázs (1975-) (élettanász)
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001-es BibID:	BIBFORM062728
Első szerző:	Kovács Adrienn (molekuláris biológus)
Cím:	Direct presynaptic and indirect astrocyte-mediated mechanisms both contribute to endocannabinoid signaling in the pedunculopontine nucleus of mice / Kovács A., Bordás Cs., Bíró T., Hegyi Z., Antal M., Szücs P., Pál B.
Dátum:	2017
ISSN:	1863-2653 1863-2661
Megjegyzések:	The pedunculopontine nucleus (PPN), a cholinergic nucleus of the reticular activating system, is known to be involved in the regulation of sleep and wakefulness. Endogenous and exogenous cannabinoids, either by systemic or local administration to the pedunculopontine nucleus can both influence sleep. We previously demonstrated that activation of astrocytes by cannabinoid type 1 (CB1) receptor agonists was able to modulate the membrane potential of PPN neurons, even in the presence of blockers of fast synaptic neurotransmission. In the present work we provide evidence that synaptic inputs of PPN neurons are also affected by activation of presynaptic and astrocytic CB1 receptors.Using slice electrophysiology combined with calcium imaging, optogenetics and immunohistochemistry, we revealed a direct presynaptic inhibitory action on inhibitory postsynaptic currents, along with a mild increase of excitatory postsynaptic currents during CB1 receptor stimulation. Besides inhibition of excitatory and inhibitory neurotransmission through stimulation of presynaptic CB1 receptors, astrocyte- and mGluR-dependent tonic inhibition and excitation also developed. The mild stimulatory action of CB1 receptor activation on excitatory neurotransmission is the combination of astrocyte-dependent tonic excitation on excitatory neurons and the canonical presynaptic CB1 receptor activation and consequential inhibition of excitatory synaptic neurotransmission, whereas the astrocyte-dependent stimulatory action was not observed on inhibitory neurotransmission within the PPN.Our findings demonstrate that endocannabinoids act in the PPN via a dual pathway, consisting of a direct presynaptic and an indirect, astrocyte-mediated component, regulating synaptic strength and neuronal activity via independent mechanisms.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban pedunculopontine nucleus CB1 receptor optogenetics astrocyte neuromodulation
Megjelenés:	Brain Structure & Function 222 : 1 (2017), p. 247-266. -
További szerzők:	Bordás Csilla Bíró Tamás (1968-) (élettanász) Hegyi Zoltán (1983-) (molekuláris biológus) Antal Miklós (1951-) (orvos, anatómus) Szűcs Péter (1974-) (kutatóorvos) Pál Balázs (1975-) (élettanász)
Pályázati támogatás:	Nemzeti Agykutatási Program KTIA_13_NAP-A-I/10 Egyéb Nemzeti Agykutatási Program KTIA_NAP_13-1-2013-0001 Egyéb Nemzeti Agykutatási Program KTIA_NAP_13-2-2014-0005 Egyéb MTA-TKI 242 MTA TÁMOP-4.2.2.B-15/1/KONV-2015-0001 TÁMOP
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001-es BibID:	BIBFORM054574
035-os BibID:	PMID: 25061872
Első szerző:	Oláh Attila (élettanász)
Cím:	Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes / Attila Oláh, Balázs I. Tóth, István Borbíró, Koji Sugawara, Attila G. Szöllősi, Gabriella Czifra, Balázs Pál, Lídia Ambrus, Jennifer Kloepper, Emanuela Camera, Matteo Ludovici, Mauro Picardo, Thomas Voets, Christos C. Zouboulis, Ralf Paus, Tamás Bíró
Dátum:	2014
ISSN:	0021-9738
Megjegyzések:	The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including arachidonic acid and a combination of linoleic acid and testosterone, and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels. Activation of TRPV4 interfered with the prolipogenic ERK1/2 MAPK pathway and resulted in the downregulation of nuclear receptor interacting protein-1 (NRIP1), which influences glucose and lipid metabolism, thereby inhibiting sebocyte lipogenesis. CBD also exerted complex antiinflammatory actions that were coupled to A2a adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of the NF-KB signaling. Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	The Journal of Clinical Investigation. - 124 : 9 (2014), p. 3713-3724. -
További szerzők:	Tóth István Balázs (1978-) (élettanász) Borbíró István (1982-) (biokémikus, molekuláris biológus) Sugawara, Koji Szöllősi Attila Gábor (1982-) (élettanász) Czifra Gabriella (1975-) (élettanász) Pál Balázs (1975-) (élettanász) Ambrus Lídia (1986-) (élettanász) Kloepper, Jennifer E. Camera, Emanuela Ludovici, Matteo Picardo, Mauro Voets, Thomas Zouboulis, Christos C. (1960-) (bőrgyógyász) Paus, Ralf Bíró Tamás (1968-) (élettanász)
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001-es BibID:	BIBFORM018462
Első szerző:	Rusznák Zoltán (élettanász)
Cím:	Differential distribution of TASK-1, TASK-2 and TASK-3 immunoreactivities in the rat and human cerebellum / Rusznak, Z., Pocsai, K., Kovacs, I., Por, A., Pal, B., Biro, T., Szücs, G.
Dátum:	2004
ISSN:	1420-682X
Megjegyzések:	In this work, the distributions of some acidsensitivetwo-pore-domain K+ channels (TASK-1, TASK-2 and TASK-3) were investigated in the rat and human cerebellum. Astrocytes situated in rat cerebellar tissuesections were positive for TASK-2 channels. Purkinjecells were strongly stained and granule cells and astrocytes were moderately positive for TASK-3. Astrocytesisolated from the hippocampus, cerebellum and cochlearnucleus expressed TASK channels in a primary tissueculture. Our results suggest that TASK channel expressionmay be significant in the endoplasmic reticulum ofthe astrocytes. The human cerebellum showed weakTASK-2 immunolabelling. The pia mater, astrocytes,Purkinje and granule cells demonstrated strong TASK-1and TASK-3 positivities. The TASK-3 labelling wasstronger in general, but it was particularly intense in thePurkinje cells and pia mater.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban TASK immunopositivity astrocyte culture cerebellum endoplasmic reticulum human brain
Megjelenés:	Cellular And Molecular Life Sciences. - 61 : 12 (2004), p. 1532-1542. -
További szerzők:	Pocsai Krisztina (1978-) (élettanász) Kovács Ilona (1965-) (patológus) Pór Ágnes Pál Balázs (1975-) (élettanász) Bíró Tamás (1968-) (élettanász) Szűcs Géza (1948-) (élettanász)
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