44 research outputs found
N-methyl-D-aspartate (NMDA) receptor composition modulates dendritic spine morphology in striatal medium spiny neurons.
No full textDendritic spines of medium spiny neurons represent an essential site of information processing between NMDA and dopamine receptors in striatum. Even if activation of NMDA receptors in the striatum has important implications for synaptic plasticity and disease states, the contribution of specific NMDA receptor subunits still remains to be elucidated. Here, we show that treatment of corticostriatal slices with NR2A antagonist NVP-AAM077 or with NR2A blocking peptide induces a significant increase of spine head width. Sustained treatment with D1 receptor agonist (SKF38393) leads to a significant decrease of NR2A-containing NMDA receptors and to a concomitant increase of spine head width. Interestingly, co-treatment of corticostriatal slices with NR2A antagonist (NVP-AAM077) and D1 receptor agonist augmented the increase of dendritic spine head width as obtained with SKF38393. Conversely, NR2B antagonist (ifenprodil) blocked any morphological effect induced by D1 activation. These results indicate that alteration of NMDA receptor composition at the corticostriatal synapse contributes not only to the clinical features of disease states such as experimental parkinsonism but leads also to a functional and morphological outcome in dendritic spines of medium spiny neurons
Impact of Proestrus on Gene Expression in the Medial Preoptic Area of Mice
No full textThe antero-ventral periventricular zone (AVPV) and medial preoptic area (MPOA) have been recognized as gonadal hormone receptive regions of the rodent brain that—via wiring to gonadotropin-releasing hormone (GnRH) neurons—contribute to orchestration of the preovulatory GnRH surge. We hypothesized that neural genes regulating the induction of GnRH surge show altered expression in proestrus. Therefore, we compared the expression of 48 genes obtained from intact proestrous and metestrous mice, respectively, by quantitative real-time PCR (qPCR) method. Differential expression of 24 genes reached significance (p < 0.05). Genes upregulated in proestrus encoded neuropeptides (kisspeptin (KP), galanin (GAL), neurotensin (NT), cholecystokinin (CCK)), hormone receptors (growth hormone secretagogue receptor, μ-opioid receptor), gonadal steroid receptors (estrogen receptor alpha (ERα), progesterone receptor (PR), androgen receptor (AR)), solute carrier family proteins (vesicular glutamate transporter 2, vesicular monoamine transporter 2), proteins of transmitter synthesis (tyrosine hydroxylase (TH)) and transmitter receptor subunit (AMPA4), and other proteins (uncoupling protein 2, nuclear receptor related 1 protein). Proestrus evoked a marked downregulation of genes coding for adenosine A2a receptor, vesicular gamma-aminobutyric acid (GABA) transporter, 4-aminobutyrate aminotransferase, tachykinin precursor 1, NT receptor 3, arginine vasopressin receptor 1A, cannabinoid receptor 1, ephrin receptor A3 and aldehyde dehydrogenase 1 family, member L1. Immunocytochemistry was used to visualize the proteins encoded by Kiss1, Gal, Cck and Th genes in neuronal subsets of the AVPV/MPOA of the proestrous mice. The results indicate that gene expression of the AVPV/MPOA is significantly modified at late proestrus including genes that code for neuropeptides, gonadal steroid hormone receptors and synaptic vesicle transporters. These events support cellular and neuronal network requirements of the positive estradiol feedback action and contribute to preparation of the GnRH neuron system for the pre-ovulatory surge release
Proestrus Differentially Regulates Expression of Ion Channel and Calcium Homeostasis Genes in GnRH Neurons of Mice
No full textIn proestrus, the changing gonadal hormone milieu alters the physiological properties of GnRH neurons and contributes to the development of the GnRH surge. We hypothesized that proestrus also influences the expression of different ion channel genes in mouse GnRH neurons. Therefore, we performed gene expression profiling of GnRH neurons collected from intact, proestrous and metestrous GnRH-GFP transgenic mice, respectively. Proestrus changed the expression of 37 ion channel and 8 calcium homeostasis-regulating genes. Voltage-gated sodium channels responded with upregulation of three alpha subunits (Scn2a1, Scn3a, and Scn9a). Within the voltage-gated potassium channel class, Kcna1, Kcnd3, Kcnh3, and Kcnq2 were upregulated, while others (Kcna4, Kcnc3, Kcnd2, and Kcng1) underwent downregulation. Proestrus also had impact on inwardly rectifying potassium channel subunits manifested in enhanced expression of Kcnj9 and Kcnj10 genes, whereas Kcnj1, Kcnj11, and Kcnj12 subunit genes were downregulated. The two-pore domain potassium channels also showed differential expression with upregulation of Kcnk1 and reduced expression of three subunit genes (Kcnk7, Kcnk12, and Kcnk16). Changes in expression of chloride channels involved both the voltage-gated (Clcn3 and Clcn6) and the intracellular (Clic1) subtypes. Regarding the pore-forming alpha-1 subunits of voltage-gated calcium channels, two (Cacna1b and Cacna1h) were upregulated, while Cacna1g showed downregulation. The ancillary subunits were also differentially regulated (Cacna2d1, Cacna2d2, Cacnb1, Cacnb3, Cacnb4, Cacng5, Cacng6, and Cacng8). In addition, ryanodine receptor 1 (Ryr1) gene was downregulated, while a transient receptor potential cation channel (Trpm3) gene showed enhanced expression. Genes encoding proteins regulating the intracellular calcium homeostasis were also influenced (Calb1, Hpca, Hpcal1, Hpcal4, Cabp7, Cab 39l, and Cib2). The differential expression of genes coding for ion channel proteins in GnRH neurons at late proestrus indicates that the altering hormone milieu contributes to remodeling of different kinds of ion channels of GnRH neurons, which might be a prerequisite of enhanced cellular activity of GnRH neurons and the subsequent surge release of the neurohormone
Altered Expression of Genes Encoding Neurotransmitter Receptors in GnRH Neurons of Proestrous Mice
No full textGonadotropin-releasing hormone (GnRH) neurons play a key role in the central regulation of reproduction. In proestrous female mice, estradiol triggers the pre-ovulatory GnRH surge, however, its impact on the expression of neurotransmitter receptor genes in GnRH neurons has not been explored yet. We hypothesized that proestrus is accompanied by substantial changes in the expression profile of genes coding for neurotransmitter receptors in GnRH neurons. We compared the transcriptome of GnRH neurons obtained from intact, proestrous, and metestrous female GnRH-GFP transgenic mice, respectively. About 1500 individual GnRH neurons were sampled from both groups and their transcriptome was analyzed using microarray hybridization and real-time PCR. In this study, changes in mRNA expression of genes involved in neurotransmitter signaling were investigated. Differential gene expression was most apparent in GABA-ergic (Gabbr1, Gabra3, Gabrb3, Gabrb2, Gabrg2), glutamatergic (Gria1, Gria2, Grin1, Grin3a, Grm1, Slc17a6), cholinergic (Chrnb2, Chrm4) and dopaminergic (Drd3, Drd4), adrenergic (Adra1b, Adra2a, Adra2c), adenosinergic (Adora2a, Adora2b), glycinergic (Glra), purinergic (P2rx7), and serotonergic (Htr1b) receptors. In concert with these events, expression of genes in the signaling pathways downstream to the receptors, i.e., G-proteins (Gnai1, Gnai2, Gnas), adenylate-cyclases (Adcy3, Adcy5), protein kinase A (Prkaca, Prkacb) protein kinase C (Prkca) and certain transporters (Slc1a4, Slc17a6, Slc6a17) were also changed. The marked differences found in the expression of genes involved in neurotransmitter signaling of GnRH neurons at pro- and metestrous stages of the ovarian cycle indicate the differential contribution of these neurotransmitter systems to the induction of the pre-ovulatory GnRH surge, the known prerequisite of the subsequent hormonal cascade inducing ovulation
Ghrelin Decreases Firing Activity of Gonadotropin-Releasing Hormone (GnRH) Neurons in an Estrous Cycle and Endocannabinoid Signaling Dependent Manner.
No full textThe orexigenic peptide, ghrelin is known to influence function of GnRH neurons, however, the direct effects of the hormone upon these neurons have not been explored, yet. The present study was undertaken to reveal expression of growth hormone secretagogue receptor (GHS-R) in GnRH neurons and elucidate the mechanisms of ghrelin actions upon them. Ca(2+)-imaging revealed a ghrelin-triggered increase of the Ca(2+)-content in GT1-7 neurons kept in a steroid-free medium, which was abolished by GHS-R-antagonist JMV2959 (10µM) suggesting direct action of ghrelin. Estradiol (1nM) eliminated the ghrelin-evoked rise of Ca(2+)-content, indicating the estradiol dependency of the process. Expression of GHS-R mRNA was then confirmed in GnRH-GFP neurons of transgenic mice by single cell RT-PCR. Firing rate and burst frequency of GnRH-GFP neurons were lower in metestrous than proestrous mice. Ghrelin (40nM-4μM) administration resulted in a decreased firing rate and burst frequency of GnRH neurons in metestrous, but not in proestrous mice. Ghrelin also decreased the firing rate of GnRH neurons in males. The ghrelin-evoked alterations of the firing parameters were prevented by JMV2959, supporting the receptor-specific actions of ghrelin on GnRH neurons. In metestrous mice, ghrelin decreased the frequency of GABAergic mPSCs in GnRH neurons. Effects of ghrelin were abolished by the cannabinoid receptor type-1 (CB1) antagonist AM251 (1µM) and the intracellularly applied DAG-lipase inhibitor THL (10µM), indicating the involvement of retrograde endocannabinoid signaling. These findings demonstrate that ghrelin exerts direct regulatory effects on GnRH neurons via GHS-R, and modulates the firing of GnRH neurons in an ovarian-cycle and endocannabinoid dependent manner
A kisagy születés utáni fejlődésének plaszticitása = Postnatal development plasticity of the cerebellum
No full textVizsgáltuk a kisagy különböző sejttípusainak születés utáni vándorlását és integrálódását. A sejtek tér-időbeli eloszlásának részletes vizsgálatából következtettünk a kisagykéregre jellemző sejtes szerkezet kialakulásának dinamikájára. Megállapítottuk, hogy a Purkinje sejtek mintegy egyharmada, a Lugaro sejtek, az unipoláris ecsetsejtek és a molekuláris réteg interneuronjai csak a peri-és posztnatális fejlődési periódusban, és sajátságos, elhúzódó, többnyire hetekig tartó időintervallumban jelennek meg végleges helyükön. A kisagykéreg szerkezetének születés utáni kialakulása igen érzékeny különböző endogén vagy exogén ártalmakra, és jelentős mértékben megzavarható brómdezoxi uridin (BrdU) szisztémás alkalmazásával. A BrdU-t 50 ug/g testsúly dózisban alkalmazva a születés után 6 illetve 12 napon keresztül, a szomatikus és idegrendszeri fejlődés retardációja, illetve az idegrendszer károsodása figyelhető meg C56Bl6 egereken. A szemcsesejtek - BrdU össz-dózisától függő hánya - elpusztul, a Purkinje sejtek pedig nem képesek a ganglionáris monolayer-be rendeződni. Zavart szenved a szemcsesejtek, továbbá a kisagykéreg molekuláris rétegében található interneuronok születés utáni vándorlása is. A kisagykéreg morfológiai károsodását a mozgáskoordináció zavarai kísérik. Posztantális BrdU kezelés - kisebb mértékben - retardálja a szomatoszenzoros kéreg fejlődését is, ami a kérgi sejtek hiperexcitabilitásában, és fokozott "seizure" érzékenységében nyilvánul meg. | We have investigated the postnatal migration and integration of several cerebellocortical neuronal types, based on detailed spatio-temporal analysis of the distribution of the different neuronal populations. We concluded, that about one third of the Purkinje cells, the Lugaro cells, the unipolar brush cells as well as the interneurons of the molecular layer occupy their place in the cerebellocortical cytoarchitectonics during a prolonged perinatal-postnatal developmental period, which is characteristic of the given neuron. The postnatal build up of the cerebellar cortex is rather sensitive to different endogenous or exogenous noxas, and can be disturbed by systemic application of 5-bromo-2'- deoxyuridine (BrdU). Postnatal BrdU treatment by 50 ug/g b.w. BrdU for 6 and 12 days after birth results in the retardation of somatic and neuronal developmnet in C57Bl6 mice. Dose dependent proportion of granule cells is going to die, high number of the Purkinje cells remain in ectopic position and many more are not able to align into the ganglionic monolayer. Postnatal migration of cerebellar granule cells and the interneurons of the molecular layer are also disturbed. The morphological damage of the cerebellar cortex is followed by a disturbed movement-coordination. Postnatal BrdU application, in a lesser extent, results in the retardation of the development of somatosensory cortex too, followed by increased hyperexcitability and enhanced seizure susceptibility
The spatio-temporal segregation of GAD forms defines distinct GABA signaling functions in the developing mouse olfactory system and provides novel insights into the origin and migration of GnRH neurons.
No full textGABA (gamma-aminobutyric acid) has a dual role as an inhibitory neurotransmitter in the adult central nervous system (CNS) and as a signaling molecule exerting largely excitatory actions during development. The rate-limiting step of GABA synthesis is catalyzed by two glutamic acid decarboxylase isoforms GAD65 and GAD67 co-expressed in the GABAergic neurons of the CNS. Here we report that the two GADs show virtually non-overlapping expression patterns consistent with distinct roles in the developing peripheral olfactory system. GAD65 is expressed exclusively in undifferentiated neuronal progenitors confined to the proliferative zones of the sensory vomeronasal and olfactory epithelia. In contrast GAD67 is expressed in a subregion of the non-sensory epithelium/vomeronasal organ epithelium containing the putative GnRH progenitors and GnRH neurons migrating from this region through the frontonasal mesenchyme (FNM) into the basal forebrain. Only GAD67+, but not GAD65+ cells accumulate detectable GABA. We further demonstrate that GAD67 and its embryonic splice variant EGAD concomitant with GnRH are dynamically regulated during GnRH neuronal migration in vivo and in two immortalized cell lines representing migratory (GN11) and post-migratory (GT1-7) stage GnRH neurons, respectively. Analysis of GAD65/67 single and double knock-out (KO) embryos revealed that the two GADs play complementary (inhibitory) roles in GnRH migration ultimately modulating the speed and/or direction of GnRH migration. Our results also suggest that GAD65 and GAD67/EGAD characterized by distinct subcellular localization and kinetics have disparate functions during olfactory system development mediating proliferative and migratory responses putatively through specific subcellular GABA pools. (c) 2014 Wiley Periodicals, Inc. Develop Neurobiol, 2014
A Magyar Tudományos Akadémia Műszaki Tudományok Osztályának közleményei
No full text25. kötet / 1-4. szám 1
CSANÁDI GYÖRGY: A közlekedéstudomány, a közlekedéspolitika, és a gyakorlati közlekedés összefüggései a szocialista és a tőkés társadalmi rendszerben
LISKA JÓZSEF: Szinkronizált indukciós motorok gerjesztése
WINTER ERNŐ: Nagy élettartamú oxidkatódok wolframmagfémmel
VIDÉKY EMIL: A goniometria kiterjesztése és projektív relativitások az involut geometriában
CSONKA PÁL: Egyetlen lépcsőhorony mentén terhelt gyámolított lépcsők fokainak hajlító igénybevétele
CSONKA PÁL: Pelikán J. kifejtési tételnek mértani igazolása
SZIDAROVSZKY JÁNOS: Függőhidak újabb elmélete a lehajlás figyelembevételével
CSONKA PÁL: Szerkesztő eljárás a külpontos igénybevétel feszültségképletében előforduló állandók meghatározására
VASTAGH GÁBOR: A szokolyahutai vasgyártás története
BALOGH ARTUR: A torzióslengés determinánsegyenletének alkalmazása az önlengésszámok kiszámítására
BORBÉLY SAMU: Hengerszimmetrikus bugák felhevítéséről IV.: Hengerszimmetrikus hőátadási folyamat vizsgálata hőmérséklettől függő termikus paraméterekkel
BARKÁSZ EMIL: Kepler egyenletének iteráció nélküli algebrai megoldása
SITKEI GYÖRGY: A forgattyúház relatív térfogatának hatása a szívási folyamatra
SITKEI GYÖRGY: Karburátoros motorok égésfolyamatai
SITKEI GYÖRGY: Az égés lefolyása Diesel-motorban
VÁCZ ISTVÁN: Különböző adalékokkal gyártott wolframdrótok kilépési munkái
CSONKA PÁL: Csonka János élete és munkássága
FÁY CSABA - KISBOCSKÓI LÁSZLÓ - BÉRCZI SÁNDOR: Fordulatszámbeállító és elektronikus rendszerű mérőberendezések vízgépvizsgálatokhoz
KÖNYVSZEMLE
PANTÓ GÁBOR: vendel MIklós: A kőzetmeghatározás módszertana. Akadémiai Kiadó, 1959. 754 o.
RÉTI PÁL: P. J. Djatschenko: Verschleissuntersuchungen mit Hilfe radioaktiver Isotope. VEB Verlag Technik Berlin, 1958.128 l.
SÁLYI ISTVÁN, IFJ.: Terplán Zénó: Mechanizmusok. Tankönyvkiadó, Budapest, 1959. 292 o.
TERPLÁN ZÉNÓ: A Nehézipari Műszaki Egyetem közleményei III. kötet. Miskolc, 1959. 480 o.
CSONKA PÁL: Palotás László: Építőanyagok I. köt.: Általános anyagismeret. A fa. A fémek. Akadémiai Kiadó, 1959. 463 olda
