@article{MTMT:2981932, title = {Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems}, url = {https://m2.mtmt.hu/api/publication/2981932}, author = {Köles, László and Kató, Erzsébet and Hanuska, Adrienn and Zádori, Zoltán Sándor and Al-Khrasani, Mahmoud and Zelles, Tibor and Rubini, P and Illes, P}, doi = {10.1007/s11302-015-9480-5}, journal-iso = {PURINERG SIGNAL}, journal = {PURINERGIC SIGNALLING}, volume = {12}, unique-id = {2981932}, issn = {1573-9538}, year = {2016}, eissn = {1573-9546}, pages = {1-24}, orcid-numbers = {Köles, László/0000-0001-6708-0269; Kató, Erzsébet/0000-0001-5786-0405; Hanuska, Adrienn/0000-0002-5031-9250; Zádori, Zoltán Sándor/0000-0001-7312-618X; Al-Khrasani, Mahmoud/0000-0001-8488-3266; Zelles, Tibor/0000-0002-0357-0469} } @article{MTMT:2080979, title = {The medial habenula contains a specific nonstellate subtype of astrocyte expressing the ectonucleotidase NTPDase2}, url = {https://m2.mtmt.hu/api/publication/2080979}, author = {Gampe, K and Hammer, K and Kittel, Ágnes and Zimmermann, H}, doi = {10.1002/glia.22402.}, journal-iso = {GLIA}, journal = {GLIA}, volume = {60}, unique-id = {2080979}, issn = {0894-1491}, abstract = {ATP-mediated synaptic transmission represents the only transmitter-gated Ca(2+) -entry pathway in neurons of the rodent medial habenula. In addition to direct purinergic receptor-mediated synaptic inputs, the medial habenula contains purinergic systems that modulate synaptic transmission. Purinergic signaling is modulated or terminated by ectonucleotidase, nucleotide-hydrolyzing enzymes of the cell surface. Here we identify the major ectonucleotidase responsible for the hydrolysis of extracellular ATP in the mouse medial habenula as ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2), using immunostaining and enzyme histochemistry. Double labeling experiments reveal that the enzyme is expressed by astrocytes enwrapping the densely packed neurons and also the myelinated fiber bundles of the stria medullaris. NTPDase2 immunoreactivity is absent from the lateral habenula. The analysis of mice expressing enhanced green fluorescent protein under the promoter of glial fibrillary acidic protein revealed that the medial habenula harbors a highly polar type of astrocytes with very long laminar cellular processes, untypical for grey matter astrocytes. Its morphology strongly differs from that of the stellate astrocytes in the adjacent lateral habenula. Our results suggest that the mouse medial habenula contains a specific perineuronal nonstellate subtype of astrocyte that expresses the ectonucleotidase NTPDase2 and is in a strategic position to modulate purinergic transmission in this subnucleus. (c) 2012 Wiley Periodicals, Inc.}, year = {2012}, eissn = {1098-1136}, pages = {1860-1870} } @article{MTMT:1990302, title = {Ablation of TNAP function compromises myelination and synaptogenesis in the mouse brain}, url = {https://m2.mtmt.hu/api/publication/1990302}, author = {Hanics, János and Barna, János and Xiao, J and Millán, J L and Fonta, C and Négyessy, László}, doi = {10.1007/s00441-012-1455-z}, journal-iso = {CELL TISSUE RES}, journal = {CELL AND TISSUE RESEARCH}, volume = {349}, unique-id = {1990302}, issn = {0302-766X}, abstract = {Mutations in the tissue-nonspecific alkaline phosphatase (TNAP) gene can result in skeletal and dental hypomineralization and severe neurological symptoms. TNAP is expressed in the synaptic cleft and the node of Ranvier in normal adults. Using TNAP knockout (KO) mice (Akp2 -/-), we studied synaptogenesis and myelination with light- and electron microscopy during the early postnatal days. Ablation of TNAP function resulted in a significant decrease of the white matter of the spinal cord accompanied by ultrastructural evidence of cellular degradation around the paranodal regions and a decreased ratio and diameter of the myelinated axons. In the cerebral cortex, myelinated axons, while present in wild-type, were absent in the Akp2 -/- mice and these animals also displayed a significantly increased proportion of immature cortical synapses. The results suggest that TNAP deficiency could contribute to neurological symptoms related to myelin abnormalities and synaptic dysfunction, among which epilepsy, consistently present in the Akp2 -/- mice and observed in severe cases of hypophosphatasia. © 2012 Springer-Verlag.}, year = {2012}, eissn = {1432-0878}, pages = {459-471}, orcid-numbers = {Hanics, János/0000-0003-3305-2440; Barna, János/0000-0002-4394-2175; Négyessy, László/0000-0002-4369-0406} } @article{MTMT:1412197, title = {Layer-specific activity of tissue non-specific alkaline phosphatase in the human neocortex}, url = {https://m2.mtmt.hu/api/publication/1412197}, author = {Négyessy, László and Xiao, J and Kántor, Orsolya and Kovács, Gábor Géza and Palkovits, Miklós and Dóczi, Tamás Péter and Renaud, L and Baksa, Gábor and Glasz, Tibor and Ashaber, Mária and Barone, P and Fonta, C}, doi = {10.1016/j.neuroscience.2010.10.049}, journal-iso = {NEUROSCIENCE}, journal = {NEUROSCIENCE}, volume = {172}, unique-id = {1412197}, issn = {0306-4522}, abstract = {The ectoenzyme tissue non-specific alkaline phosphatase (TNAP) is mostly known for its role in bone mineralization. However, in the severe form of hypophosphatasia, TNAP deficiency also results in epileptic seizures, suggesting a role of this enzyme in brain functions. Accordingly, TNAP activity was shown in the neuropil of the cerebral cortex in diverse mammalian species. However in spite of its clinical significance, the neuronal localization of TNAP has not been investigated in the human brain. By using enzyme histochemistry, we found an unprecedented pattern of TNAP activity appearing as an uninterrupted layer across diverse occipital-, frontal- and temporal lobe areas of the human cerebral cortex. This marked TNAP-active band was localized infragranulary in layer 5 as defined by quantitative comparisons on parallel sections stained by various techniques to reveal the laminar pattern. On the contrary, TNAP activity was localized in layer 4 of the primary visual and somatosensory cortices, which is consistent with earlier observations on other species. This result suggests that the expression of TNAP in the thalamo-recipient granular layer is an evolutionary conserved feature of the sensory cortex. The observations of the present study also suggest that diverse neurocognitive functions share a common cerebral cortical mechanism depending on TNAP activity in layer 5. In summary, the present data point on the distinctive role of layer 5 in cortical computation and neurological disorders caused by TNAP dysfunctions in the human brain.}, year = {2011}, eissn = {1873-7544}, pages = {406-418}, orcid-numbers = {Négyessy, László/0000-0002-4369-0406; Kántor, Orsolya/0000-0002-1388-8294; Kovács, Gábor Géza/0000-0003-3841-5511; Palkovits, Miklós/0000-0003-0578-0387; Glasz, Tibor/0000-0003-2947-2733} } @article{MTMT:1482495, title = {The Role of Extracellular Adenosine in Chemical Neurotransmission in the Hippocampus and Basal Ganglia: Pharmacological and Clinical Aspects.}, url = {https://m2.mtmt.hu/api/publication/1482495}, author = {Sperlágh, Beáta and Vizi, E. Szilveszter}, doi = {10.2174/156802611795347564}, journal-iso = {CURR TOP MED CHEM}, journal = {CURRENT TOPICS IN MEDICINAL CHEMISTRY}, volume = {11}, unique-id = {1482495}, issn = {1568-0266}, abstract = {Now there is general agreement that the purine nucleoside adenosine is an important neuromodulator in the central nervous system, playing a crucial role in neuronal excitability and synaptic/non-synaptic transmission in the hippocampus and basal ganglia. Adenosine is derived from the breakdown of extra- or intracellular ATP and is released upon a variety of physiological and pathological stimuli from neuronal and non-neuronal sources, i.e. from glial cells and exerts effects diffusing far away from release sites. The resultant elevation of adenosine levels in the extracellular space reaches micromolar level, and leads to the activation A(1), A(2A), A(2B) and A(3) receptors, localized to pre- and postsynaptic as well as extrasynaptic sites. Activation of presynaptic A(1) receptors inhibits the release of the majority of transmitters including glutamate, acetylcholine, noradrenaline, 5-HT and dopamine, whilst the stimulation of A(2A) receptors facilitates the release of glutamate and acetylcholine and inhibits the release of GABA. These actions underlie modulation of neuronal excitability, synaptic plasticity and coordination of neural networks and provide intriguing target sites for pharmacological intervention in ischemia and Parkinson's disease. However, despite that adenosine is also released during ischemia, A(1) adenosine receptors do not participate in the modulation of excitotoxic glutamate release, which is nonsynaptic and is due to the reverse operation of transporters. Instead, extrasynaptic A(1) receptors might be responsible for the neuroprotection afforded by A(1) receptor activation.}, year = {2011}, eissn = {1873-4294}, pages = {1034-1046}, orcid-numbers = {Vizi, E. Szilveszter/0000-0002-9557-4597} } @article{MTMT:1228647, title = {Ecto-nucleoside triphosphate diphosphohydrolase 3 in the ventral and lateral hypothalamic area of female rats: morphological characterization and functional implications}, url = {https://m2.mtmt.hu/api/publication/1228647}, author = {Kiss, Dávid Sándor and Zsarnovszky, Attila and Horvath, Krisztina and Győrffy, Andrea and Bartha, Tibor and Novák-Hazai, Diana and Sótonyi, Péter and Somogyi, Virág and Frenyó V., László and Diano, Sabrina}, doi = {10.1186/1477-7827-7-31}, journal-iso = {REPROD BIOL ENDOCRIN}, journal = {REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY}, volume = {7}, unique-id = {1228647}, issn = {1477-7827}, abstract = {Abstract Background: Based on its distribution in the brain, ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3) may play a role in the hypothalamic regulation of homeostatic systems, including feeding, sleep-wake behavior and reproduction. To further characterize the morphological attributes of NTPDase3-immunoreactive (IR) hypothalamic structures in the rat brain, here we investigated: 1.) The cellular and subcellular localization of NTPDase3; 2.) The effects of 17-estradiol on the expression level of hypothalamic NTPDase3; and 3.) The effects of NTPDase inhibition in hypothalamic synaptosomal preparations. Methods: Combined light- and electron microscopic analyses were carried out to characterize the cellular and subcellular localization of NTPDase3-immunoreactivity. The effects of estrogen on hypothalamic NTPDase3 expression was studied by western blot technique. Finally, the effects of NTPDase inhibition on mitochondrial respiration were investigated using a Clark-type oxygen electrode. Results: Combined light- and electron microscopic analysis of immunostained hypothalamic slices revealed that NTPDase3-IR is linked to ribosomes and mitochondria, is predominantly present in excitatory axon terminals and in distinct segments of the perikaryal plasma membrane. Immunohistochemical labeling of NTPDase3 and glutamic acid decarboxylase (GAD) indicated that -amino-butyric-acid- (GABA) ergic hypothalamic neurons do not express NTPDase3, further suggesting that in the hypothalamus, NTPDase3 is predominantly present in excitatory neurons. We also investigated whether estrogen influences the expression level of NTPDase3 in the ventrobasal and lateral hypothalamus. A single subcutaneous injection of estrogen differentially increased NTPDase3 expression in the medial and lateral parts of the hypothalamus, indicating that this enzyme likely plays region-specific roles in estrogen-dependent hypothalamic regulatory mechanisms. Determination of mitochondrial respiration rates with and without the inhibition of NTPDases confirmed the presence of NTPDases, including NTPDase3 in neuronal mitochondria and showed that blockade of mitochondrial NTPDase functions decreases state 3 mitochondrial respiration rate and total mitochondrial respiratory capacity. Conclusions: Altogether, these results suggest the possibility that NTPDases, among them NTPDase3, may play an estrogen-dependent modulatory role in the regulation of intracellular availability of ATP needed for excitatory neuronal functions including neurotransmission.}, year = {2009}, eissn = {1477-7827}, orcid-numbers = {Győrffy, Andrea/0000-0001-7110-1464} } @article{MTMT:1637688, title = {Immunolocalization of ecto-nucleoside triphosphate diphosphohydrolase 3 in rat brain: Implications for modulation of multiple homeostatic systems including feeding and sleep-wake behaviors}, url = {https://m2.mtmt.hu/api/publication/1637688}, author = {Belcher, SM and Zsarnovszky, Attila and Crawford, PA and Hemani, H and Spurling, L and Kirley, TL}, doi = {10.1016/j.neuroscience.2005.08.086}, journal-iso = {NEUROSCIENCE}, journal = {NEUROSCIENCE}, volume = {137}, unique-id = {1637688}, issn = {0306-4522}, abstract = {Three anti-peptide antisera were raised against three distinct amino acid sequences of ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3), characterized by Western blot analyses, and used to determine the distribution of NTPDase3 protein in adult rat brain. The three antisera all yielded similar immunolocalization data, leading to increased reliability of the results obtained. Unlike NTPDase1 and NTPDase2, NTPDase3 immunoreactivity was detected exclusively in neurons. Immunoreactivity was localized primarily to axon-like structures with prominent staining of presynaptic elements. Specific perikaryal immunostaining was detected primarily in scattered neurons near the lateral hypothalamic area and the perifornical nucleus. High densities of immunoreactive axon-like fibers were present in midline regions of the forebrain and midbrain. Highly scattered NTPDase3 positive fibers were observed in the cerebral cortex, the hippocampal formation, and the basal ganglia. Moreover, very high densities of immunostained fibers were detected in the mediobasal hypothalamus, with the overall mesencephalic pattern of staining associated closely with hormone responsive nuclei. High densities of NTPDase3 positive terminals were also associated with noradrenergic neurons. However, co-immunolocalization studies revealed clearly that NTPDase3 immunoreactivity was not localized within the noradrenaline cells or terminals. In contrast, nearly all of the NTPDase3 immunopositive hypothalamic cells, and most fibers in the mid- and hindbrain, also expressed hypocretin-1/orexin-A. The overall pattern of expression and co-localization with hypocretin-1/orexin-A suggests that NTPDase3, by regulating the extracellular turnover of ATP, may modulate feeding, sleep-wake, and other behaviors through diverse homeostatic systems. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.}, year = {2006}, eissn = {1873-7544}, pages = {1331-1346} } @article{MTMT:210664, title = {Postnatal development of alkaline phosphatase activity correlates with the maturation of neurotransmission in the cerebral cortex}, url = {https://m2.mtmt.hu/api/publication/210664}, author = {Fonta, C and Négyessy, László and Renaud, L and Barone, P}, doi = {10.1002/cne.20524}, journal-iso = {J COMP NEUROL}, journal = {JOURNAL OF COMPARATIVE NEUROLOGY}, volume = {486}, unique-id = {210664}, issn = {0021-9967}, year = {2005}, eissn = {1096-9861}, pages = {179-196}, orcid-numbers = {Négyessy, László/0000-0002-4369-0406} } @article{MTMT:210665, title = {Areal and subcellular localization of the ubiquitous alkaline phosphatase in the primate cerebral cortex: Evidence for a role in neurotransmission}, url = {https://m2.mtmt.hu/api/publication/210665}, author = {Fonta, C and Négyessy, László and Renaud, L and Barone, P}, doi = {10.1093/cercor/bhh021}, journal-iso = {CEREB CORTEX}, journal = {CEREBRAL CORTEX}, volume = {14}, unique-id = {210665}, issn = {1047-3211}, year = {2004}, eissn = {1460-2199}, pages = {595-609}, orcid-numbers = {Négyessy, László/0000-0002-4369-0406} }