95 research outputs found
Idegi regeneráció és befolyásolási lehetőségei alacsonyabbrendű és emlős idegrendszerben = Neuroregeneration and its modulation in invertebrate and mammalian nervous systems
Az "Idegi regeneráciĂł Ă©s befolyásolási lehetĹ‘sĂ©gei alacsonyabbrendű Ă©s emlĹ‘s idegrendszerben" ifjĂşsági OTKA tervezete szerint kĂ©t nagy tĂ©ma körĂ© csoportosĂtottam az elvĂ©gzendĹ‘ feladatokat. Az elsĹ‘ rĂ©szben az idegi regeneráciĂł Ă©s a hipofĂzis adenilát cikláz aktiválĂł polipeptid (PACAP) elĹ‘fordulását vizsgáltam alacsonyabbrendű idegrendszerben. Kimutattuk a PACAP Ă©s receptorainak eloszlását Eisenia idegrendszerĂ©ben. Embrionális szövetekben, kokonfolyadĂ©kban, Ă©s a szaporodási idĹ‘szakban a clitellaris terĂĽleten is magas a PACAP szint. A dĂşclánc átvágása után a PACAP upregulálĂłdik, Ă©s a trofikus faktorokat szállĂtĂł coelomasejtek is magas PACAP koncentráciĂłt tartalmaznak. Helixben, egy másik gerinctelen fajban kimutattuk, hogy a PACAP antiapoptotikus hatással rendelkezik. Ezek alapján a PACAP funkcionálisan is valĂłszĂnűleg konzervált peptid, Ă©s gerinctelenekben is szĂ©les körben elĹ‘fordul. A pályázat második rĂ©szĂ©ben az idegi lĂ©ziĂł regeneráciĂłs lehetĹ‘sĂ©geit vizsgáltam patkányban. Kimutattuk, hogy a PACAP számos idegrendszeri lĂ©ziĂłban vĂ©dĹ‘ hatást nyĂşjt, pl. in vivo Parkinson kĂłrban, excitotoxicus lĂ©ziĂłban Ă©s retinális degeneráciĂłban. In vitro a PACAP az apoptĂłzissal szemben más szöveteket, sejteket is vĂ©d, mint pl. endothelsejteket Ă©s szĂvizomsejteket. Ezen sejtekben Ă©s a retinában kimutattuk, hogy a PACAP az antiapoptotikus Ăştvonalakat stimulálja, mĂg a proapoptotikus Ăştvonalakat gátolja. Ezen támogatás segĂtsĂ©gĂ©vel Ă©s feltĂĽntetĂ©sĂ©vel összesen 23 közlemĂ©ny szĂĽletett (IF:42,9). | The investigation planned in the OTKA ?Neuroregeneration and its modulation in invertebrate and mammalian nervous system? was subdivided in two major categories. First, regeneration and the occurrence of pituitary adenylate cyclase activating polypeptide (PACAP) was investigated in the invertebrate nervous system. We have shown that PACAP and its receptors occur in the nervous system of Eisenia. Levels of PACAP are very high during embryonic development, in the embryo, in the cocoon fluid, and in the clitellar region in the reproductive age. After transection of the ventral cord, PACAP is strongly upregulated, and its concentration is very high in the celomic cells which transport trophic factors. In another invertebrate species, in Helix, we showed that the peptide has antiapoptotic effects. Based on these data, PACAP seems to be a functionally conserved peptide. In the second part, I investigated the possible modulation of nerve regeneration by PACAP in rats. We have shown that PACAP has protective effects in various nerve injuries, like in vivo models of Parkinson`s disease, excitotoxic lesion and retinal degeneration. PACAP protects not only neuronal cells, but other tissues as well against apoptosis, like endothelial cells and cardiomyocytes. We have shown that PACAP stimulates antiapoptotic signaling molecules and inhibits proapoptotic signaling pathways in these cells and in the retina in vivo. With the help of this grant, we have published 23 manuscripts (IF:42.9)
PACAP neuroprotektĂv hatása Parkinson-kĂłr Ă©s ĂşjszĂĽlöttkori neuronális károsodás patkány modellekben = The neuroprotective effects of PACAP in rat models of Parkinson's disease and neonatal neuronal damage
A pályázat szerves folytatása volt a korábbi T034491 projektnek. A jelen pályázatban PACAP neuroprotektĂv hatásainak vizsgálatát folytattuk, az eredeti terv szerint kĂ©t fĹ‘ tĂ©ma körĂ© csoportosĂtva: a PACAP hatása bazális ganglionok károsodásában Ă©s ĂşjszĂĽlöttkori agykárosodásban. Kimutattuk, hogy a PACAP csökkenti a dopaminerg sejtpusztulást a substantia nigrában Ă©s jelentĹ‘sen javĂtja a neurolĂłgiai tĂĽneteket patkány Parkinson kĂłr modellben. LeĂrtuk az unilaterális substantia nigra roncsolás modell Ă©s ebben a PACAP protektĂv hatásainak kor Ă©s nemfĂĽggĂ©sĂ©t. Igazoltuk a PACAP vĂ©dĹ‘ hatását Huntington chorea, neurotrauma modellekben, valamint toxicus Ă©s ischemiás retinadegeneráciĂłban. Igazoltuk, hogy a PACAP nemcsak neuroprotektĂv, hanem általános citoprotektĂv tulajdonságĂş: vĂ©dĹ‘ hatást fejt ki szĂvizom-Ă©s endothelsejtekben, vese Ă©s bĂ©lischemiában. A hatásmechanizmust tekintve igazoltuk, hogy ezen rendszerekben a PACAP antiapoptotikus tulajdonságĂş, in vitro Ă©s in vivo gátolja a proapoptotikus Ă©s aktiválja az antiapoptotikus jelátviteli Ăştvonalakat. Eddig nem ismert jelátviteli Ăştvonalak igazolásán kĂvĂĽl leĂrtuk, hogy a PACAP hatása jelentĹ‘s kĂĽlönbsĂ©geket mutat a kor, nem, napi ritmus Ă©s sejttĂpustĂłl fĂĽggĹ‘en. ĂšjszĂĽlöttkori lĂ©ziĂłkban (toxicus, hypoxiás) leĂrtuk a kora postnatalis neuronális fejlĹ‘dĂ©st, Ă©s kimutattuk a PACAP vĂ©dĹ‘ hatását bizonyos reflexfejlĹ‘dĂ©si mintázatra. A támogatás segĂtsĂ©gĂ©vel szĂĽletett közlemĂ©nyek összesĂtett impakt faktora 139,807 (absztraktok nĂ©lkĂĽl). | We continued the investigation on the neuroprotective effects of PACAP. The focus of our research was to examine the neuroprotective effects in models of basal ganglia diseases and neonatal brain injuries. We showed that PACAP treatment ameliorates the substantia nigra dopaminergic cell loss and improves the neurological deficits in a model of Parkinson`s disease. We examined how this unilateral substantia nigra degeneration model and the effects of PACAP depend on age and gender. We have provided evidence that PACAP is also protective in models of Huntington chorea, brain trauma, toxic and ischemic retinal degeneration. We have also shown that PACAP is not only neuroprotective, but is a general cytoprotective peptide: it has protective effects in cardiomyocytes, endothelial cells, kidney and intestinal ischemia. Considering the neuroprotective mechanism, we showed that PACAP has antiapoptotic effects in these models, it activates the antiapoptotic and inhibits the proapoptotic signaling pathways both in vitro and in vivo. In addition to providing evidence for new neuroprotective signaling mechanisms, we also showed that the protective effects of PACAP depend on age, gender, diurnal cycle and cell type.We described the early postnatal neurobehavioral development in toxic and hypoxic injuries and the protective effects of PACAP on some neurological reflexes. The impact factor of the publications with the help of this grant is 139.807 (without abstracts)
Mesenchymal Stromal Cell derived Extracellular Vesicles reduce Hypoxia-Ischaemia Induced Perinatal Brain Injury
Background: Neonatal hypoxic ischemic (HI) insult is a leading cause of disability and death in newborns, with therapeutic hypothermia being the only currently available clinical intervention. Thus there is a great need for adjunct and novel treatments for enhanced or alternative post-HI neuroprotection. Extracellular vesicles (EVs) derived from mesenchymal stromal/stem cells (MSCs) have recently been shown to exhibit regenerative effects in various injury models. Here we present findings showing neuroprotective effects of MSC-derived EVs in the Rice-Vannucci model of severe HI-induced neonatal brain insult.
Method: MSC-derived EVs were applied intranasally immediately post HI-insult and behavioural outcomes were observed 48 h following MSC-EV treatment, as assessed by negative geotaxis. Brains were thereafter excised and assessed for changes in glial responses, cell death and neuronal loss as markers of damage at 48 h post HI-insult.
Results: Brains of the MSC-EV treated group showed a significant decrease in microglial activation, cell death and percentage tissue volume loss in multiple brain regions, compared to the control-treated groups. Furthermore, negative geotaxis test showed improved behavioural outcomes at 48 h following MSC-EV treatment.
Conclusion: Our findings highlight the clinical potential of using MSC-derived EVs following neonatal hypoxia-ischaemia
A felnĹ‘ttkori káros szerhasználat összefĂĽggĂ©se a felnĹ‘ttkori negatĂv Ă©letesemĂ©nyekkel, a traumatizált gyermekkorral Ă©s a pszicholĂłgiai immunrendszerrel
INST: L_135Kutatásunk cĂ©lja feltĂ©rkĂ©pezni a gyermekkori traumák, a felnĹ‘ttkori negatĂv Ă©letesemĂ©nyek Ă©s a pszicholĂłgiai immunrendszer kapcsolatát a felnĹ‘ttkori káros szerhasználattal
Time-course of the regeneration of the earthworm cerebral ganglion with special reference to serotonergic elements.
In the present study we give a detailed description of the time-course of regeneration following the removal of the cerebral ganglion in the earthworm, Eisenia fetida . Cerebral ganglia were removed by cutting the circumpharyngeal connectives and regeneration was examined at different time intervals by serotonin immunohistochemistry. The number of serotonergic fibers gradually increased between days 3-6, rebuilding the neuronal network of the cerebral ganglion. By day 10, the scar tissue was filled with an interwoven fiber network, which clearly outlined the central neuropil of the cerebral ganglion. The first immunoreactive nerve cells appeared on the 25th day following the removal of the cerebral ganglion. According to our observations, the cerebral ganglion regains its original structure 70 days after removal. It can be suggested based on our results that the cerebral ganglion mainly regenerates from the subesophageal ganglion through the circumpharyngeal connective
Memory, cAMP, and PACAP-a phylogenetically conserved function? Studies in Lymnea stagnalis
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved polypeptide, which, along with its receptors (PAC1-R, VPAC1, and VPAC2), is expressed in both vertebrate and invertebrate nervous systems. In the first part of the present study, we showed the presence of PACAP in Lymnea stagnalis by mass spectrometry and investigated whether PACAP elevates cAMP in cerebral ganglia. VIP, PACAP, and maxadilan increased cAMP levels by ~47, 79, and 82% of control levels, respectively, and this effect could be blocked by the co-application of the antagonist PACAP6-38 and maxadilan antagonist
Protective effects of pituitary adenylate cyclase activating polypeptide against neurotoxic agents
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide highly expressed in the central and peripheral nervous system, where it exerts several neuromodulatory functions and is an important trophic and protective factor. PACAP has been shown to activate several protective pathways, mainly through its specific PAC1 receptor and protein kinase A, C and MAP kinases downstream. It has been shown to have very potent neuroprotective actions against different neurotoxic agents both in vitro and in vivo. The aim of the present review is to provide an overview on the neurotoxic injuries against which PACAP exerts protection, and to give an insight into its protective mechanism. We give a summary of the neuroprotective effects against the most commonly used neurotoxic agents, such as 6-OHDA, MPTP, glutamate and some less well-known neurotoxic compounds. Also endogenous PACAP has neuroprotective effects, known from studies in PACAP knockout mice or from blocking endogenous effects by antagonists. Altogether, the vast amount of data for the neuroprotective effects of PACAP give a firm background for its endogenous role as part of the neuroprotective machinery and its possible future therapeutic use as a neuroprotective factor
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