Neuroprotective effects of gonadal hormons and neurosteroids: in vivo and in virto studies  Page description

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Details of project

  
Identifier
43436
Type K
Principal investigator Párdutz, Árpád
Title in Hungarian A nemi hormonok és neuroszteroidok neuroprotektív szerepe: in vivo és in vitro vizsgálatok
Title in English Neuroprotective effects of gonadal hormons and neurosteroids: in vivo and in virto studies
Panel Neurosciences
Department or equivalent Institute of Biophysics (HUN-REN Biological Research Centre Szeged)
Participants Balog, János Attila
Hoyk, Zsófia
Siklós, László
Varga, Csaba
Starting date 2003-01-01
Closing date 2006-12-31
Funding (in million HUF) 13.160
FTE (full time equivalent) 0.00
state closed project





 

Final report

  
Results in Hungarian
A jelen pályázat keretében elvégzett vizsgálatok célja azon sejt és molekuláris szintű mechanizmusok tanulmányozása volt, melyek az öregedésből ill. az agyi sérülésekből adódó morfológiai és funkcionális károsodások enyhítését lehetővé teszik. Különböző állatmodelleken a női nemi hormon (ösztrogén) ill. az egyik neuroszteroid, dehydroepiandoszteron (DHEA) hatását tanulmányoztuk az idegi sérüléseket követő reakciókra. Legfontosabb megállapításaink: A patkány szaglógumó kísérletes deafferentációját követően kialakuló reaktív asztrogliózist az ösztrogén és a DHEA egyaránt csökkenti. Aromatáz gátló fadrozol segítségével igazoltuk, hogy a protektív hatás kialakulásáért nem maga a neuroszteroid, hanem az abból lokálisan szintetizálódó 17β-ösztadiol a felelős. Patkány agykéregben hideg lézióval előidézett sérülés mértékét dehydroepiandoszteron szulfát (DHEAS) kezelésével csökkenteni lehet. Figyelemreméltó, hogy ilyen körülmények között a neuroszteroid protektív hatása kifejezettebb, ha azt a sérülést követően alkalmazzuk. BrdU-val történő jelöléssel igazoltuk, hogy a patkány szaglógumójában az ösztrogén régió-specifikus módon hat az agyterületen folyó neurogenezisre, az újonnan integrálódó interneuronok túlélésére.
Results in English
In the present project we studied the process of neurodegeneration occurring during normal ageing or induced by injury. By using different animal models we have studied the effects of estrogen and the neurosteroid dehydroepiandrosterone (DHEA) on the neuronal and glial reactions following neuronal injury. Our aim was to identify those cellular and molecular mechanisms, which were responsible for the neuroprotective effects of these steroids. In deafferentated olfactory bulb of adult rats we have demonstrated that DHEA attenuates the glial reaction to denervation and may regulate glial plasticity in the olfactory glomeruli. With the use of aromatase inhibitor fadrozole we have provided evidences that these effects are likely to be mediated by the local conversion of DHEA to 17 β-estradiol. In a focal cortical cold lesion model we have shown that the size of injury can be decreased by dehydroepiandrosterone sulphate (DHEAS). Our observations clearly show that DHEAS is neuroprotective both in pre- and post-traumatic administration and these results suggest that it may be of substantial therapeutic benefit for the treatment of traumatic injury. By using the mitotic marker BrdU we have found that cells destined to the glomerular and granule cell layers react in the same way to chronic estrogen treatment, and the effect of 17 β-estradiol on the neurogenesis and neuron survival is region specific within the adult olfactory bulb.
Full text http://real.mtak.hu/1075/
Decision
Yes





 

List of publications

  
Parducz A; Kurunczi A; Csakvari E; Varga Cs; Hoyk Zs: Estradiol induced structural synaptic remodelling in the hypothalamus., In: Proceedings of the 6th Multinational Congress on Microscopy -European Extension-Pula Croatia June 1-5, 2003. p. 47-48, 2003
Parducz A; Csakvari E; Kurunczi A; Zsarnovszky A; Horvath TL: Effect of estradiol on the axo-somatic synapses of neuroendocrine cells in the arcuate nucleus of adult rats., In: Proceedings of 6th IBRO World Congress of Neurosciences, Prague, July 10-15, 2003; p. 4203, 2003
Parducz A: The role of gonadal steroids in synaptic plasticity: morphological and functional consequences., Proceedings of CEERC Brain Research Symposium, Ljubjana, Slovenia May 9, 2003: pp. 27-29, 2003
Peterfi Z; Churchill L; Hajdu I; Obal JrF; Krueger JM; Parducz A: Fos-immunoreactivity in the hypothalamus: dependency on the diurnal rhythm, sleep, gender, and estrogen., Neuroscience, 124(3): 695-707, 2004
Hoyk Zs;Parducz A; Garcia-Segura LM: Dehydroepiandrosterone regulates astroglia reaction to denervation of olfactory glomeruli., Glia, 48(3): 207-216, 2004
Csákvári E; Kurunczi A;Gyenes A; Párducz Á: Neuroplastic changes induced by estrogen in the arcuate nucleus., In: Clinical Neuroscience 57: P13, 2004
Hoyk Zs; Garcia-Segura LM; Parducz A: DHEA influence on astroglia reaction in the denervated olfactory bulb in the rat., In: Clinical Neuroscience 57: P25, 2004
Kurunczi A; Csákvári E; Gyenes A; Párducz Á: Effect of 17 b-estradiol on the expression of ERa and ERb in hypothalamic nuclei., In: Clinical Neuroscience 57: P37, 2004
Varga Cs; Hoyk Zs; Parducz A: Immature neurons detected by PSA-NCAM/Bcl-2 immunoreactivity in the adult neocortex of guinea pig, rabbit, cat and rhesus monkey., In: Clinical Neuroscience 57: P69, 2004
Parducz A, Csákvári E; Kurunczi A;Gyenes A; Varga C; Hoyk Zs: Estrogen-induced synaptic plasticity in the central nervous system., In: 4th FENS Forum Lisbon, Portugal, July 10-14, 2004. Abstracts, p. 236, 2004
Hoyk Zs; Garcia-Segura LM; Parducz A: Dehydroepiandrosterone influence on astroglia reaction in the denervatied olfactory bulb in the rat., In: 4th FENS Forum Lisbon, Portugal, July 10-14, 2004.Abstracts, p. 432, 2004
Juhasz-Vedres G, Rozsa E, Dobszay MB, Kis Z, Wolfing J, Toldi J, Parducz A, Farkas T: Dehydroepiandrosterone sulfate (DHEAS) is neuroprotective when administered either pre- or post-injury in a focal cortical cold lesion model., Endocrinology, 147(2): 683-6, 2006
Vezer T, Papp A, Kurunczi A, Parducz A, Naray M, Nagymajtenyi L: Behavioral and neurotoxic effects seen during and after subchronic exposure of rats to organic mercury., Environmental Toxicology and Pharmacology, 19: 785-796, 2005
George O, Parducz A, Dupret D, Kharouby M, Le Moal M, Piazza PV, Mayo W: Smad-dependent alterations of PPT cholinergic neurons as a pathophysiological mechanism of age-related sleep-dependent memory impairments., Neurobiol. Aging, 2027: 1848-582, 2006
Parducz A, Hajszan T, Maclusky NJ, Hoyk Z, Csakvari E, Kurunczi A, Prange-Kiel J, Leranth C: Synaptic remodeling induced by gonadal hormones: neuronal plasticity as a mediator of neuroendocrine and behavioral responses to steroids., Neuroscience. 138: 977-85, 2006
Parducz A, Hoyk S, Kurunczi A, Csakvari E, Kis Zs, Garcia-Segura LM: Estradiol-induced synaptic plasticity: functional consequences., Trabajos del Instituto Cajal, Vol. 80. p. 130-131, 2005
Csákvári E, Kurunczi A., Hoyk Zs., Gyenes A., Párducz A: Cyclic changes in synaptic connectivity in the arcuate nucleus., In: Clinical Neuroscience, 58: P23, 2005
Hoyk Zs., Varga Cs. Párducz A: Estradiol modulation of neurogenesis and PSA-NCAM expression in the dentate gyrus of the hippocampus of the adult rat., In: Clinical Neuroscience, 58: P42, 2005
Kurunczi A., Csákvári E., Hoyk Zs., Krizbai I., Párducz A: Age- and hormone-related changes in the expression of GAP-43 in the olfactory bulb., In: Clinical Neuroscience, 58: P58, 2005
Parducz A, Hoyk Zs, Garcia-Segura LM: Estradiol-induced synaptic remodeling in the arcuate nucleus: morphological and functional consequences., International IBRO Wokshop, Budapest, 2006. Clinical Neuroscience 59: P52, 2006
Gyenes A, Hoyk Zs, Csákváry E, Siklós L, Parducz Á: Effects of estradiol on the microglia reaction following nerve injury., International IBRO Wokshop, Budapest, 2006. Clinical Neuroscience 59: P24, 2006
Gyenes A, Pósa A, Kurunczi A, Hoyk Zs, Csákváry E, Siklós L, László F, Parducz Á: Raloxifen induces changes in the expression of estrogen receptor in the arcuate nucleus., 5th Forum of European Neuroscience, Wien, July 8-12, 2006
Csákváry E, Kurunczi A, Gyenes A, Hoyk Zs, Parducz Á: The specificity of estradiol-induced synaptic remodeling in the rat arcuate nucleus., 5th Forum of European Neuroscience, Wien, July 8-12, 2006
Vezér T, Pásztor-Turák M, Papp A, Parducz Á: Behavioral and histochemical effects of subacute tetraethyl lead exposure in rats., 5th Forum of European Neuroscience, Wien, July 8-12, 2006
Hoyk Zs, Varga Cs, Párducz A: Estrogen-induced region specific decrease in the density of 5-bromo-2-deoxyuridine-labeled cells in the olfactory bulb of adult female rats., Neuroscience. 141: 1919-24, 2006
Csákvári E, Hoyk Zs, Garcia-Ovejero D, Garcia-Segura LM, Párducz Á: Fluctuation of synapse density in the arcuate nucleus during the estrous cycle., Neuroscience. 2006 Dec 7; [Epub ahead of print], 2006
Csakvari E, Hoyk S, Szajli A, Kurunczi A, Gyenes A, Berger A, Parducz A: Lesion-induced glial reaction in the rat olfactory bulb: effect of DHEA and DHEA derivatives., Trabajos del Instituto Cajal, Vol. 81. p. 237, 2007



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