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001-es BibID:	BIBFORM069485
Első szerző:	Farkas József
Cím:	Early Neurobehavioral Development of Mice Lacking Endogenous PACAP / Farkas J., Sandor B., Tamas A., Kiss P., Hashimoto H., Nagy A. D., Fulop B. D., Juhasz T., Manavalan S., Reglodi D.
Dátum:	2017
Megjegyzések:	Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide. In addition to its diverse physiological roles, PACAP has important functions in the embryonic development of various tissues, and it is also considered as a trophic factor during development and in the case of neuronal injuries. Data suggest that the development of the nervous system is severely affected by the lack of endogenous PACAP. Short-term neurofunctional outcome correlates with long-term functional deficits; however, the early neurobehavioral development of PACAP-deficient mice has not yet been evaluated. Therefore, the aim of the present study was to describe the postnatal development of physical signs and neurological reflexes in mice partially or completely lacking PACAP. We examined developmental hallmarks during the first 3 weeks of the postnatal period, during which period most neurological reflexes and motor coordination show most intensive development, and we describe the neurobehavioral development using a complex battery of tests. In the present study, we found that PACAP-deficient mice had slower weight gain throughout the observation period. Interestingly, mice partially lacking PACAP weighed significantly less than homozygous mice. There was no difference between male and female mice during the first 3 weeks. Some other signs were also more severely affected in the heterozygous mice than in the homozygous mice, such as air righting, grasp, and gait initiation reflexes. Interestingly, incisor teeth erupted earlier in mice lacking PACAP. Motor coordination, shown by the number of foot-faults on an elevated grid, was also less developed in PACAP-deficient mice. In summary, our results show that mice lacking endogenous PACAP have slower weight gain during the first weeks of development and slower neurobehavioral development regarding a few developmental hallmarks.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Knockout Neurodevelopment Neuropeptide Reflex Trophic factor
Megjelenés:	Journal of molecular neuroscience. - 61 : 4 (2017), p. 468-478. -
További szerzők:	Sándor Balázs Tamás Andrea (Idegtudomány) (Pécs) Kiss Péter (Pécs) Hashimoto, Hitoshi Nagy András Dávid Fülöp Balázs Dániel (Orvosi alapkutatások) Juhász Tamás (1976-) (biológus, orvosbiológus) Manavalan, Sridharan Reglődi Dóra (Idegtudományok)
Pályázati támogatás:	K104984 OTKA K119759 OTKA GINOP-2.3.2-15-2016-00050 GINOP TAMOP 4.2.4.A/2-11-1-2012-0001 TÁMOP
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001-es BibID:	BIBFORM103634
035-os BibID:	(WOS)000472082700006 (Scopus)85051646952
Első szerző:	Fülöp Balázs Dániel (Orvosi alapkutatások)
Cím:	Altered Notch Signaling in Developing Molar Teeth of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)-Deficient Mice / B. D. Fulop, B. Sandor, E. Szentleleky, E. Karanyicz, D. Reglodi, B. Gaszner, R. Zakany, H. Hashimoto, T. Juhasz, A. Tamas
Dátum:	2019
ISSN:	0895-8696
Megjegyzések:	Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with neuroprotective and neurotrophic effects. This suggests its influence on the development of teeth, which are, similarly to the nervous system, ectoderm and neural crest derivatives. Our earlier studies have shown morphological differences between wild-type (WT) and PACAP-deficient mice, with upregulated sonic hedgehog (SHH) signaling in the lack of PACAP. Notch signaling is a key element of proper tooth development by regulating apoptosis and cell proliferation. In this study, our main goal was to evaluate the possible effects of PACAP on Notch signaling pathway. Immunohistochemical staining was performed of Notch receptors (Notch1, 2, 3, 4), their ligands [deltalike protein (DLL)1, 3, 4, Jagged1, 2], and intracellular target molecules [CSL (CBF1 humans/Su (H) Drosophila/LAG1 Caenorhabditis elegans transcription factor); TACE (TNF-? converting enzyme), NUMB] in molar teeth of 5-day-old WT, and homozygous and heterozygous PACAP-deficient mice. We measured immunopositivity in the enamel-producing ameloblasts and dentin-producing odontoblasts. Notch2 receptor and DLL1 expression were elevated in ameloblasts of PACAPdeficient mice compared to those in WT ones. The expression of CSL showed similar results both in the ameloblasts and odontoblasts. Jagged1 ligand expression was elevated in the odontoblasts of homozygous PACAP-deficient mice compared to WT mice. Other Notch pathway elements did not show significant differences between the genotype groups. The lack of PACAP leads to upregulation of Notch pathway elements in the odontoblast and ameloblast cells. The underlying molecular mechanisms are yet to be elucidated; however, we propose SHH-dependent and independent processes. We hypothesize that this compensatory upregulation of Notch signaling by the lack of PACAP could represent a salvage pathway in PACAP-deficient animals.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk PACAP-deficient mice Notch signaling DLL1, 3, 4, Jagged1, 2 Notch1, 2, 3, 4 CSL TACE NUMB Development of molar tooth
Megjelenés:	Journal of Molecular Neuroscience. - 68 : 3 (2019), p. 377-388. -
További szerzők:	Sándor Balázs Szentléleky Eszter (fogászat) Karanyicz Edina Reglődi Dóra (Idegtudományok) Gaszner Balázs (Neuroanatómia) Zákány Róza (1963-) (anatómus-, kötőszövetbiológus) Hashimoto, Hitoshi Juhász Tamás (1976-) (biológus, orvosbiológus) Tamás Andrea (Idegtudomány) (Pécs)
Pályázati támogatás:	2.3.2-15-2016-00050 BPEPSYS^ GINOP 3.6.3-VEKOP-16-15 2017-00008 EFOP 3.6.2-16-2017-00008 EFOP 3.6.1- 16.2016.00004 EFOP 4.2.4.A/2-11-1-2012-0001 TAMOP
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001-es BibID:	BIBFORM054231
035-os BibID:	PMID: 25112419
Első szerző:	Sándor Balázs
Cím:	Structural and Morphometric Comparison of the Molar Teeth in Pre-eruptive Developmental Stage of PACAP-Deficient and Wild-Type Mice / B. Sandor, K. Fintor, Sz. Felszeghy, T. Juhasz, D. Reglodi, L. Mark, P. Kiss, A. Jungling, B. D. Fulop, A. D. Nagy, H. Hashimoto, R. Zakany, A. Nagy, A. Tamas
Dátum:	2014
ISSN:	0895-8696
Megjegyzések:	Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic neuropeptide with widespread distribution. It plays pivotal role in neuronal development. PACAP-immunoreactive fibers have been found in the tooth pulp, and recently, it has been shown that PACAP may also play a role in the regeneration of the periodontium after luxation injuries. However, there is no data about the effect of endogenous PACAP on tooth development. Ectodermal organogenesis including tooth development is regulated by different members of bone morphogenetic protein (BMP), fibroblast growth factor (FGF), hedgehog (HH), and Wnt families. There is also a growing evidence to support the hypothesis that PACAP interacts with sonic hedgehog (SHH) receptor (PTCH1) and its downstream target (Gli1) suggesting its role in tooth development. Therefore, our aim was to study molar tooth development in mice lacking endogenous PACAP. In this study morphometric, immunohistochemical and structural comparison of molar teeth in pre-eruptive developmental stage was performed on histological sections of 7-day-old wild-type and PACAP-deficient mice. Further structural analysis was carried out with Raman microscope. The morphometric comparison of the 7-day-old samples revealed that the dentin was significantly thinner in the molars of PACAP-deficient mice compared to wild-type animals. Raman spectra of the enamel in wild-type mice demonstrated higher diversity in secondary structure of enamel proteins. In the dentin of PACAP-deficient mice higher intracrystalline disordering in the hydroxyapatite molecular structure was found. We also obtained altered SHH, PTCH1 and Gli1 expression level in secretory ameloblasts of PACAP-deficient mice compared to wild-type littermates suggesting that PACAP might play an important role in molar tooth development and matrix mineralization involving influence on SHH signaling cascade.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Journal of Molecular Neuroscience. - 54 : 3 (2014), p. 331-334. -
További szerzők:	Fintor K. Felszeghy Szabolcs Béla (1972-) (fogorvos, anatómus, kötőszövetbiológus) Juhász Tamás (1976-) (biológus, orvosbiológus) Reglődi Dóra (Idegtudományok) Mark L. Kiss Péter (Pécs) Jungling Adél Fülöp Balázs Dániel (Orvosi alapkutatások) Nagy András Dávid Hashimoto, Hitoshi Zákány Róza (1963-) (anatómus-, kötőszövetbiológus) Nagy Ákos Tamás Andrea (Idegtudomány) (Pécs)
Pályázati támogatás:	PTE-MTA Lendület Egyéb K104984 OTKA PD109644 OTKA 4.2.2.A-11/1/KONV-2012-0024 TÁMOP 4.2.4A/2-11-1-2012-0001 TÁMOP Bolyai Ösztöndíj Egyéb Debreceni Egyetem RH/885/2013 Egyéb Grants-in-Aid for Scientific Research KAKENHI, 26293020, 26670122 Egyéb
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