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001-es BibID:	BIBFORM059232
Első szerző:	Hrabovszky Erik
Cím:	Substance P Immunoreactivity Exhibits Frequent Colocalization with Kisspeptin and Neurokinin B in the Human Infundibular Region / Erik Hrabovszky, Beáta Á. Borsay, Kálmán Rácz, László Herczeg, Philippe Ciofi, Stephen R. Bloom, Mohammad A. Ghatei, Waljit S. Dhillo, Zsolt Liposits
Dátum:	2013
ISSN:	1932-6203
Megjegyzések:	Neurons synthesizing neurokinin B (NKB) and kisspeptin (KP) in the hypothalamic arcuate nucleus represent important upstream regulators of pulsatile gonadotropin-releasing hormone (GnRH) neurosecretion. In search of neuropeptides co-expressed in analogous neurons of the human infundibular nucleus (Inf), we have carried out immunohistochemical studies of the tachykinin peptide Substance P (SP) in autopsy samples from men (21-78 years) and postmenopausal (53-83 years) women. Significantly higher numbers of SP-immunoreactive (IR) neurons and darker labeling were observed in the Inf of postmenopausal women than in age-matched men. Triple-immunofluorescent studies localized SP immunoreactivity to considerable subsets of KP-IR and NKB-IR axons and perikarya in the infundibular region. In postmenopausal women, 25.1% of NKB-IR and 30.6% of KP-IR perikarya contained SP and 16.5% of all immunolabeled cell bodies were triple-labeled. Triple-, double- and single-labeled SP-IR axons innervated densely the portal capillaries of the infundibular stalk. In quadruple-labeled sections, these axons formed occasional contacts with GnRH-IR axons. Presence of SP in NKB and KP neurons increases the functional complexity of the putative pulse generator network. First, it is possible that SP modulates the effects of KP and NKB in axo-somatic and axo-dendritic afferents to GnRH neurons. Intrinsic SP may also affect the activity and/or neuropeptide release of NKB and KP neurons via autocrine/paracrine actions. In the infundibular stalk, SP may influence the KP and NKB secretory output via additional autocrine/paracrine mechanisms or regulate GnRH neurosecretion directly. Finally, possible co-release of SP with KP and NKB into the portal circulation could underlie further actions on adenohypophysial gonadotrophs.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Immunohistochemistry techniques neurons axons immune serum neuropeptides nerve fibers estrogens sheep
Megjelenés:	Plos One. - 8 : 8 (2013), p. e72369. -
További szerzők:	Borsay Beáta Á. (1982-) (igazságügyi orvosszakértő) Rácz Kálmán (1981-) (igazságügyi rezidens) Herczeg László (1954-) (igazságügyi orvosszakértő) Ciofi, Philippe Bloom, Stephen R. Ghatei, Mohammad A. Dhillo, Waljit S. Liposits Zsolt
Pályázati támogatás:	OTKA-K83710 OTKA OTKA-K100722 OTKA
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001-es BibID:	BIBFORM059225
Első szerző:	Hrabovszky Erik
Cím:	Orexinergic Input to Dopaminergic Neurons of the Human Ventral Tegmental Area / Erik Hrabovszky, Csilla S. Molnár, Beáta Á. Borsay, Péter Gergely, László Herczeg, Zsolt Liposits
Dátum:	2013
ISSN:	1932-6203
Megjegyzések:	The mesolimbic reward pathway arising from dopaminergic (DA) neurons of the ventral tegmental area (VTA) has been strongly implicated in reward processing and drug abuse. In rodents, behaviors associated with this projection are profoundly influenced by an orexinergic input from the lateral hypothalamus to the VTA. Because the existence and significance of an analogous orexigenic regulatory mechanism acting in the human VTA have been elusive, here we addressed the possibility that orexinergic neurons provide direct input to DA neurons of the human VTA. Dual-label immunohistochemistry was used and orexinergic projections to the VTA and to DA neurons of the neighboring substantia nigra (SN) were analyzed comparatively in adult male humans and rats. Orexin B-immunoreactive (IR) axons apposed to tyrosine hydroxylase (TH)-IR DA and to non-DA neurons were scarce in the VTA and SN of both species. In the VTA, 15.0?2.8% of TH-IR perikarya in humans and 3.2?0.3% in rats received orexin B-IR afferent contacts. On average, 0.24?0.05 and 0.05?0.005 orexinergic appositions per TH-IR perikaryon were detected in humans and rats, respectively. The majority (86?88%) of randomly encountered orexinergic contacts targeted the dendritic compartment of DA neurons. Finally, DA neurons of the SN also received orexinergic innervation in both species. Based on the observation of five times heavier orexinergic input to TH-IR neurons of the human, compared with the rat, VTA, we propose that orexinergic mechanism acting in the VTA may play just as important roles in reward processing and drug abuse in humans, as already established well in rodents.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Axons Neurons neuronal dendrites Dopamine dopaminergics drug abuse Rodents ventral tegmental area
Megjelenés:	Plos One. - 8 : 12 (2013), p. e83029. -
További szerzők:	Molnár Csilla S. (Budapest) Borsay Beáta Á. (1982-) (igazságügyi orvosszakértő) Gergely Péter (1974-) (igazságügyi orvosszakértő) Herczeg László (1954-) (igazságügyi orvosszakértő) Liposits Zsolt
Pályázati támogatás:	OTKA-K83710 OTKA OTKA-K100722 OTKA
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001-es BibID:	BIBFORM041250
Első szerző:	Kalló Imre
Cím:	A Novel Pathway Regulates Thyroid Hormone Availability in Rat and Human Hypothalamic Neurosecretory Neurons / Imre Kalló, Petra Mohácsik, Barbara Vida, Anikó Zeöld, Zsuzsanna Bardóczi, Ann Marie Zavacki, Erzsébet Farkas, Andrea Kádár, Erik Hrabovszky, Rafael Arrojo e Drigo, Liping Dong, László Barna, Miklós Palkovits, Beáta A. Borsay, László Herczeg, Ronald M. Lechan, Antonio C. Bianco, Zsolt Liposits, Csaba Fekete, Balázs Gereben
Dátum:	2012
ISSN:	1932-6203
Megjegyzések:	Hypothalamic neurosecretory systems are fundamental regulatory circuits influenced by thyroid hormone. Monocarboxylate-transporter-8 (MCT8)-mediated uptake of thyroid hormone followed by type 3 deiodinase (D3)-catalyzed inactivation represent limiting regulatory factors of neuronal T3 availability. In the present study we addressed the localization and subcellular distribution of D3 and MCT8 in neurosecretory neurons and addressed D3 function in their axons. Intense D3-immunoreactivity was observed in axon varicosities in the external zone of the rat median eminence and the neurohaemal zone of the human infundibulum containing axon terminals of hypophysiotropic parvocellular neurons. Immuno-electronmicroscopy localized D3 to dense-core vesicles in hypophysiotropic axon varicosities. N-STORM-superresolution-microscopy detected the active center containing C-terminus of D3 at the outer surface of these organelles. Double-labeling immunofluorescent confocal microscopy revealed that D3 is present in the majority of GnRH, CRH and GHRH axons but only in a minority of TRH axons, while absent from somatostatin-containing neurons. Bimolecular-Fluorescence-Complementation identified D3 homodimers, a prerequisite for D3 activity, in processes of GT1-7 cells. Furthermore, T3-inducible D3 catalytic activity was detected in the rat median eminence. Triple-labeling immunofluorescence and immuno-electronmicroscopy revealed the presence of MCT8 on the surface of the vast majority of all types of hypophysiotropic terminals. The presence of MCT8 was also demonstrated on the axon terminals in the neurohaemal zone of the human infundibulum. The unexpected role of hypophysiotropic axons in fine-tuned regulation of T3 availability in these cells via MCT8-mediated transport and D3-catalyzed inactivation may represent a novel regulatory core mechanism for metabolism, growth, stress and reproduction in rodents and humans.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	PLoS One (electronic resource). - 7 : 6 (2012), p. e37860. -
További szerzők:	Mohácsik Petra Vida Barbara Zeöld Anikó Bardóczi Zsuzsanna Zavacki Ann Marie Farkas Erzsébet Kádár Andrea Hrabovszky Erik Arrojo e Drigo, Rafael Dong, Liping Barna László Palkovits Miklós Borsay Beáta Á. (1982-) (igazságügyi orvosszakértő) Lechan, Ronald M. Bianco, Antonio C. Liposits Zsolt Fekete Csaba Gereben Balázs Herczeg László (1954-) (igazságügyi orvosszakértő)
Pályázati támogatás:	K81226 OTKA K81845 OTKA K69127 OTKA
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001-es BibID:	BIBFORM059183
Első szerző:	Skrapits Katalin
Cím:	Colocalization of Cocaine- and Amphetamine-Regulated Transcript with Kisspeptin and Neurokinin B in the Human Infundibular Region / Katalin Skrapits, Beáta Á. Borsay, László Herczeg, Philippe Ciofi, Stephen R. Bloom, Mohammad A. Ghatei, Waljit S. Dhillo, Zsolt Liposits, Erik Hrabovszky
Dátum:	2014
ISSN:	1932-6203
Megjegyzések:	Kisspeptin (KP)- and neurokinin B (NKB)- synthesizing neurons of the hypothalamic arcuate nucleus play a pivotal role in the regulation of pulsatile gonadotropin-releasing hormone (GnRH) secretion. Unlike in rodents and sheep, the homologous KP and NKB neurons in the human infundibular region rarely express dynorphin- but often exhibit Substance P (SP) immunoreactivity, indicating remarkable species differences in the neurochemical phenotype of these neurons. In search for additional neuropeptides in human KP and NKB neurons, we carried out immunofluorescent studies on hypothalamic sections obtained from five postmenopausal women. Colocalization experiments provided evidence for the presence of cocaine- and amphetamine-regulated transcript (CART) in 47.966.6% of KP-immunoreactive (IR) and 30.064.9% of NKB-IR perikarya and in 17.062.3% of KP-IR and 6.262.0% of NKB-IR axon varicosities. All three neuropeptides were present in 33.364.9% of KP-IR and 28.264.6% of NKB-IR somata, respectively, whereas triple-labeling showed lower incidences in KP-IR (14.361.8%) and NKB-IR (5.962.0%) axon varicosities. CART-IR KP and NKB neurons established contacts with other peptidergic cells, including GnRH-IR neurons and also sent projections to the infundibular stalk. KP and NKB fibers with CART often contained SP as well, while being distinct from CART fibers co-containing the orexigenic peptide agouti-related protein. Presence of CART in human, but not rodent, KP and NKB neurons represents a new example of species differences in the neuropeptide repertoire of mediobasal hypothalamic KP and NKB neurons. Target cells, receptor sites and physiological significance of CART in the efferent communication of KP and NKB neurons in primates require clarification.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban neurons axons nerve fibers Neuropeptides Afferent neurons rodents immune serum Immunohistochemistry techniques
Megjelenés:	Plos One. - 9 : 8 (2014), p. e103977-. -
További szerzők:	Borsay Beáta Á. (1982-) (igazságügyi orvosszakértő) Herczeg László (1954-) (igazságügyi orvosszakértő) Ciofi, Philippe Bloom, Stephen R. Ghatei, Mohammad A. Dhillo, Waljit S. Liposits Zsolt Hrabovszky Erik
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