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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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DOI
Intézményi repozitóriumban (DEA) tárolt változat
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2.

001-es BibID:BIBFORM041509
Első szerző:Hrabovszky Erik
Cím:Low degree of overlap between kisspeptin, neurokinin B, and dynorphin immunoreactivities in the infundibular nucleus of young male human subjects challenges the KNDy neuron concept / Hrabovszky E., Sipos M. T., Molnár C. S., Ciofi P., Borsay B. Á., Gergely P., Herczeg L., Bloom S. R., Ghatei M. A., Dhillo W. S., Liposits Z.
Dátum:2012
ISSN:0013-7227
Megjegyzések:Previous immunohistochemical and in situ hybridization studies of sheep, goats, and rodents indicated that kisspeptin (KP), neurokinin B (NKB), and dynorphin A (DYN) are extensively colocalized in the hypothalamic arcuate nucleus, thus providing a basis for the KP/NKB/DYN (KNDy) neuron concept; in both sexes, KNDy neuropeptides have been implicated in the generation of GnRH neurosecretory pulses and in the negative feedback effects of sexual steroids to the reproductive axis. To test the validity and limitations of the KNDy neuron concept in the human, we carried out the comparative immunohistochemical analysis of the three neuropeptides in the infundibular nucleus (Inf; also known as arcuate nucleus) and stalk of young male human individuals (<37 yr). Results of quantitative immunohistochemical experiments established that the regional densities of NKB immunoreactive (IR) perikarya and fibers, and the incidence of afferent contacts they formed onto GnRH neurons, were about 5 times as high as those of the KP-IR elements. Dual-immunofluorescent studies confirmed that considerable subsets of the NKB-IR and KP-IR cell bodies and fibers are separate, and only about 33% of NKB-IR perikarya and 75% of KP-IR perikarya were dual labeled. Furthermore, very few DYN-IR cell bodies could be visualized in the Inf. DYN-IR fibers were also rare and, with few exceptions, distinct from the KP-IR fibers. The abundance and colocalization patterns of the three immunoreactivities showed similar trends in the infundibular stalk around portal blood vessels. Together these results indicate that most NKB neurons in the Inf do not synthesize detectable amounts of KP and DYN in young male human individuals. These data call for a critical use of the KNDy neuron terminology when referring to the putative pulse generator system of the mediobasal hypothalamus. We conclude that the functional importance of these three neuropeptides in reproductive regulation considerably varies among species, between sexes, and at different ages.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Endocrinology. - 153 : 10 (2012), p. 4978-4989. -
További szerzők:Sipos Máté T. Molnár Csilla S. (Budapest) Ciofi, Philippe Borsay Beáta Á. (1982-) (igazságügyi orvosszakértő) Gergely Péter (1974-) (igazságügyi orvosszakértő) Herczeg László (1954-) (igazságügyi orvosszakértő) Bloom, Stephen R. Ghatei, Mohammad A. Dhillo, Waljit S. Liposits Zsolt
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
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