@article{MTMT:32754967,
	title = {Motoneuronal inflammasome activation triggers excessive neuroinflammation and impedes regeneration after sciatic nerve injury},
	url = {https://m2.mtmt.hu/api/publication/32754967},
	author = {Molnár, Kinga and Nógrádi, Bernát and Kristóf, Rebeka and Mészáros, Ádám and Pajer, Krisztián and Siklós, László and Nógrádi, Antal and Wilhelm, Imola Mária and Krizbai, István Adorján},
	doi = {10.1186/s12974-022-02427-9},
	journal-iso = {J NEUROINFLAMM},
	journal = {JOURNAL OF NEUROINFLAMMATION},
	volume = {19},
	unique-id = {32754967},
	abstract = {Peripheral nerve injuries are accompanied by inflammatory reactions, over-activation of which may hinder recovery. Among pro-inflammatory pathways, inflammasomes are one of the most potent, leading to release of active IL-1β. Our aim was to understand how inflammasomes participate in central inflammatory reactions accompanying peripheral nerve injury.After axotomy of the sciatic nerve, priming and activation of the NLRP3 inflammasome was examined in cells of the spinal cord. Regeneration of the nerve was evaluated after coaptation using sciatic functional index measurements and retrograde tracing.In the first 3 days after the injury, elements of the NLRP3 inflammasome were markedly upregulated in the L4-L5 segments of the spinal cord, followed by assembly of the inflammasome and secretion of active IL-1β. Although glial cells are traditionally viewed as initiators of neuroinflammation, in this acute phase of inflammation, inflammasome activation was found exclusively in affected motoneurons of the ventral horn in our model. This process was significantly inhibited by 5-BDBD, a P2X4 receptor inhibitor and MCC950, a potent NLRP3 inhibitor. Although at later time points the NLRP3 protein was upregulated in microglia too, no signs of inflammasome activation were detected in these cells. Inhibition of inflammasome activation in motoneurons in the first days after nerve injury hindered development of microgliosis in the spinal cord. Moreover, P2X4 or inflammasome inhibition in the acute phase significantly enhanced nerve regeneration on both the morphological and the functional levels.Our results indicate that the central reaction initiated by sciatic nerve injury starts with inflammasome activation in motoneurons of the ventral horn, which triggers a complex inflammatory reaction and activation of microglia. Inhibition of neuronal inflammasome activation not only leads to a significant reduction of microgliosis, but has a beneficial effect on the recovery as well.},
	keywords = {AXOTOMY; regeneration; IL-1β; motoneuron; REINNERVATION; inflammasome; sciatic nerve injury; NLRP3; extracellular ATP},
	year = {2022},
	eissn = {1742-2094},
	orcid-numbers = {Wilhelm, Imola Mária/0000-0003-2366-7337}
}

@article{MTMT:32214572,
	title = {Passive transfer of blood sera from ALS patients with identified mutations results in elevated motoneuronal calcium level and loss of motor neurons in the spinal cord of mice},
	url = {https://m2.mtmt.hu/api/publication/32214572},
	author = {Polgár, Tamás Ferenc and Meszlényi, Valéria and Nógrádi, Bernát and Körmöczy, Laura and Spisák, Krisztina and Tripolszki, Kornélia and Széll, Márta and Obál, Izabella and Engelhardt, József István and Siklós, László and Patai, Roland},
	doi = {10.3390/ijms22189994},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {22},
	unique-id = {32214572},
	issn = {1661-6596},
	year = {2021},
	eissn = {1422-0067},
	orcid-numbers = {Körmöczy, Laura/0000-0002-6789-7612; Tripolszki, Kornélia/0000-0002-7734-1992; Széll, Márta/0000-0002-0730-714X; Engelhardt, József István/0000-0002-9880-1441}
}

@article{MTMT:31850252,
	title = {Stress Resilience Is Associated with Hippocampal Synaptoprotection in the Female Rat Learned Helplessness Paradigm.},
	url = {https://m2.mtmt.hu/api/publication/31850252},
	author = {Huzián, Orsolya and Baka, Judith and Csákvári, Eszter and Dobos, Nikoletta and Leranth, Csaba and Siklós, László and Duman, Ronald S and Farkas, Tamás and Hajszán, Tibor},
	doi = {10.1016/j.neuroscience.2021.01.029},
	journal-iso = {NEUROSCIENCE},
	journal = {NEUROSCIENCE},
	volume = {459},
	unique-id = {31850252},
	issn = {0306-4522},
	abstract = {The synaptogenic hypothesis of major depressive disorder implies that preventing the onset of depressive-like behavior also prevents the loss of hippocampal spine synapses. By applying the psychoactive drugs, diazepam and fluoxetine, we investigated whether blocking the development of helpless behavior by promoting stress resilience in the rat learned helplessness paradigm is associated with a synaptoprotective action in the hippocampus. Adult ovariectomized and intact female Sprague-Dawley rats (n=297) were treated with either diazepam, fluoxetine, or vehicle, exposed to inescapable footshocks or sham stress, and tested in an active escape task to assess helpless behavior. Escape-evoked corticosterone secretion, as well as remodeling of hippocampal spine synapses at a timepoint representing the onset of escape testing were also analyzed. In ovariectomized females, treatment with diazepam prior to stress exposure prevented helpless behavior, blocked the loss of hippocampal spine synapses, and muted the corticosterone surge evoked by escape testing. Although fluoxetine stimulated escape performance and hippocampal synaptogenesis under non-stressed conditions, almost all responses to fluoxetine were abolished following exposure to inescapable stress. Only a much higher dose of fluoxetine was capable of partly reproducing the strong protective actions of diazepam. Importantly, these protective actions were retained in the presence of ovarian hormones. Our findings indicate that stress resilience is associated with the preservation of spine synapses in the hippocampus, raising the possibility that, besides synaptogenesis, hippocampal synaptoprotection is also implicated in antidepressant therapy.},
	keywords = {MAJOR DEPRESSION; CORTICOSTERONE; SYNAPTIC PLASTICITY; DIAZEPAM; fluoxetine; antidepressant resistance},
	year = {2021},
	eissn = {1873-7544},
	pages = {85-103},
	orcid-numbers = {Baka, Judith/0000-0002-8803-0217}
}

@article{MTMT:31801259,
	title = {ApoE-Targeting Increases the Transfer of Solid Lipid Nanoparticles with Donepezil Cargo across a Culture Model of the Blood–Brain Barrier},
	url = {https://m2.mtmt.hu/api/publication/31801259},
	author = {Topal, Gizem Rüya and Mészáros, Mária and Porkoláb, Gergő and Szecskó, Anikó and Polgár, Tamás Ferenc and Siklós, László and Deli, Mária Anna and Veszelka, Szilvia and Bozkir, Asuman},
	doi = {10.3390/pharmaceutics13010038},
	journal-iso = {PHARMACEUTICS},
	journal = {PHARMACEUTICS},
	volume = {13},
	unique-id = {31801259},
	issn = {1999-4923},
	year = {2021},
	eissn = {1999-4923},
	orcid-numbers = {Deli, Mária Anna/0000-0001-6084-6524}
}

@article{MTMT:31794637,
	title = {Upregulation of Nucleotide-Binding Oligomerization Domain-, LRR- and Pyrin Domain-Containing Protein 3 in Motoneurons Following Peripheral Nerve Injury in Mice},
	url = {https://m2.mtmt.hu/api/publication/31794637},
	author = {Nógrádi, Bernát and Nyúl-Tóth, Ádám and Kozma, Mihály and Molnár, Kinga and Patai, Roland and Siklós, László and Wilhelm, Imola Mária and Krizbai, István Adorján},
	doi = {10.3389/fphar.2020.584184},
	journal-iso = {FRONT PHARMACOL},
	journal = {FRONTIERS IN PHARMACOLOGY},
	volume = {11},
	unique-id = {31794637},
	abstract = {Neuronal injuries are accompanied by release and accumulation of damage-associated molecules, which in turn may contribute to activation of the immune system. Since a wide range of danger signals (including endogenous ones) are detected by the nucleotide-binding oligomerization domain-, LRR- and pyrin domain-containing protein 3 (NLRP3) pattern recognition receptor, we hypothesized that NLRP3 may become activated in response to motor neuron injury. Here we show that peripheral injury of the oculomotor and the hypoglossal nerves results in upregulation of NLRP3 in corresponding motor nuclei in the brainstem of mice. Although basal expression of NLRP3 was observed in microglia, astroglia and neurons as well, its upregulation and co-localization with apoptosis-associated speck-like protein containing a caspase activation and recruitment domain, suggesting inflammasome activation, was only detected in neurons. Consequently, increased production of active pro-inflammatory cytokines interleukin-1 beta and interleukin-18 were detected after hypoglossal nerve axotomy. Injury-sensitive hypoglossal neurons responded with a more pronounced NLRP3 upregulation than injury-resistant motor neurons of the oculomotor nucleus. We further demonstrated that the mitochondrial protector diazoxide was able to reduce NLRP3 upregulation in a post-operative treatment paradigm. Our results indicate that NLRP3 is activated in motoneurons following acute nerve injury. Blockade of NLRP3 activation might contribute to the previously observed anti-inflammatory and neuroprotective effects of diazoxide.},
	year = {2020},
	eissn = {1663-9812},
	orcid-numbers = {Wilhelm, Imola Mária/0000-0003-2366-7337}
}

@article{MTMT:31405651,
	title = {Passive transfer of sera from als patients with identified mutations evokes an increased synaptic vesicle number and elevation of calcium levels in motor axon terminals, similar to sera from sporadic patients},
	url = {https://m2.mtmt.hu/api/publication/31405651},
	author = {Meszlényi, Valéria and Patai, Roland and Polgár, Tamás Ferenc and Nógrádi, Bernát and Körmöczy, Laura and Kristóf, Rebeka and Spisák, Krisztina and Tripolszki, Kornélia and Széll, Márta and Obál, Izabella and Engelhardt, József István and Siklós, László},
	doi = {10.3390/ijms21155566},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {21},
	unique-id = {31405651},
	issn = {1661-6596},
	abstract = {Previously, we demonstrated increased calcium levels and synaptic vesicle densities in the motor axon terminals (MATs) of sporadic amyotrophic lateral sclerosis (ALS) patients. Such alterations could be conferred to mice with an intraperitoneal injection of sera from these patients or with purified immunoglobulin G. Later, we confirmed the presence of similar alterations in the superoxide dismutase 1 G93A transgenic mouse strain model of familial ALS. These consistent observations suggested that calcium plays a central role in the pathomechanism of ALS. This may be further reinforced by completing a similar analytical study of the MATs of ALS patients with identified mutations. However, due to the low yield of muscle biopsy samples containing MATs, and the low incidence of ALS patients with the identified mutations, these examinations are not technically feasible. Alternatively, a passive transfer of sera from ALS patients with known mutations was used, and the MATs of the inoculated mice were tested for alterations in their calcium homeostasis and synaptic activity. Patients with 11 different ALS-related mutations participated in the study. Intraperitoneal injection of sera from these patients on two consecutive days resulted in elevated intracellular calcium levels and increased vesicle densities in the MATs of mice, which is comparable to the effect of the passive transfer from sporadic patients. Our results support the idea that the pathomechanism underlying the identical manifestation of the disease with or without identified mutations is based on a common final pathway, in which increasing calcium levels play a central role.},
	year = {2020},
	eissn = {1422-0067},
	orcid-numbers = {Körmöczy, Laura/0000-0002-6789-7612; Tripolszki, Kornélia/0000-0002-7734-1992; Széll, Márta/0000-0002-0730-714X; Engelhardt, József István/0000-0002-9880-1441}
}

@article{MTMT:31324226,
	title = {Diazoxide blocks or reduces microgliosis when applied prior or subsequent to motor neuron injury in mice},
	url = {https://m2.mtmt.hu/api/publication/31324226},
	author = {Nógrádi, Bernát and Meszlényi, Valéria and Patai, Roland and Polgár, Tamás Ferenc and Spisák, Krisztina and Kristóf, Rebeka and Siklós, László},
	doi = {10.1016/j.brainres.2020.146875},
	journal-iso = {BRAIN RES},
	journal = {BRAIN RESEARCH},
	volume = {1741},
	unique-id = {31324226},
	issn = {0006-8993},
	abstract = {Diazoxide (DZX), an anti-hypertonic and anti-hypoglycemic drug, was shown to have anti-inflammatory effects in several injured cell types outside the central nervous system. In the brain, the neuroprotective potential of DZX is well described, however, its anticipated anti-inflammatory effect after acute injury has not been systematically analyzed. To disclose the anti-inflammatory effect of DZX in the central nervous system, an injury was induced in the hypoglossal and facial nuclei and in the oculomotor nucleus by unilateral axonal transection and unilateral target deprivation (enucleation), respectively. On the fourth day after surgery, microglial analysis was performed on tissue in which microglia were DAB-labeled and motoneurons were labeled with immunofluorescence. DZX treatment was given either prophylactically, starting 7 days prior to the injury and continuing until the animals were sacrificed, or postoperatively only, with daily intraperitoneal injections (1.25 mg/kg; in 10 mg/ml dimethyl sulfoxide in distilled water). Prophylactically + postoperatively applied DZX completely eliminated the microglial reaction in each motor nuclei. If DZX was applied only postoperatively, some microglial activation could be detected, but its magnitude was still significantly smaller than the non-DZX-treated controls. The effect of DZX could also be demonstrated through an extended period, as tested in the hypoglossal nucleus on day 7 after the operation. Neuronal counts, determined at day 4 after the operation in the hypoglossal nucleus, demonstrated no loss of motor neurons, however, an increased Feret's diameter of mitochondria could be measured, suggesting increased oxidative stress in the injured cells. The increase of mitochondrial Feret's diameter could also be prevented with DZX treatment.},
	year = {2020},
	eissn = {1872-6240},
	orcid-numbers = {Nógrádi, Bernát/0000-0001-8643-0367; Patai, Roland/0000-0002-5302-2815}
}

@article{MTMT:30722364,
	title = {Experimental motor neuron disease induced in mice with long-term repeated intraperitoneal injections of serum from ALS patients},
	url = {https://m2.mtmt.hu/api/publication/30722364},
	author = {Obál, Izabella and Nógrádi, Bernát and Meszlényi, Valéria and Patai, Roland and Ricken, Gerda and Kovács, Gábor Géza and Tripolszki, Kornélia and Széll, Márta and Siklós, László and Engelhardt, József István},
	doi = {10.3390/ijms20102573},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {20},
	unique-id = {30722364},
	issn = {1661-6596},
	abstract = {In an earlier study, signs of commencing degeneration of spinal motor neurons were induced in mice with short-term intraperitoneal injections of immunoglobulin G (IgG) taken from patients with amyotrophic lateral sclerosis (ALS). Since in that study, neither weakness nor loss of motor neurons was noted, to test whether the ALS IgG in this paradigm has the potential to evoke relentless degeneration of motor neurons, treatment with repeated injections over a longer period was carried out. Mice were systematically injected intraperitoneally with serum taken from ALS patients over a 75-day period. At selected time points, the isometric force of the limbs, number of spinal motor neurons and their intracellular calcium levels were determined. Furthermore, markers of glial activation and the motoneuronal uptake of human IgG were monitored. During this period, gliosis and progressive motoneuronal degeneration developed, which led to gradual loss of spinal motor neurons, more than 40% at day 21, along with decreasing muscle strength in the limbs. The inclusion-like accumulation of IgG appeared in the perikarya with the increase of intracellular calcium in the cell bodies and motor nerve terminals. Our results demonstrate that ALS serum can transfer motor neuron disease to mice.},
	keywords = {INTRACELLULAR CALCIUM; SERUM; DEGENERATION; ALS; motor neuron; passive transfer; IgG uptake},
	year = {2019},
	eissn = {1422-0067},
	orcid-numbers = {Kovács, Gábor Géza/0000-0003-3841-5511; Tripolszki, Kornélia/0000-0002-7734-1992; Széll, Márta/0000-0002-0730-714X; Engelhardt, József István/0000-0002-9880-1441}
}

@article{MTMT:3399566,
	title = {Niosomes decorated with dual ligands targeting brain endothelial transporters increase cargo penetration across the blood-brain barrier},
	url = {https://m2.mtmt.hu/api/publication/3399566},
	author = {Mészáros, Mária and Porkoláb, Gergő and Kiss, Lóránd and Pilbat, Ana Maria and Kóta, Zoltán and Kupihár, Zoltán and Kéri, Albert and Galbács, Gábor and Siklós, László and Tóth, András and Fülöp, Lívia and Czirjákné Csete, Mária and Sipos, Áron and Hulper, P and Sipos, Péter and Páli, Tibor and Rákhely, Gábor and Révész, Piroska and Deli, Mária Anna and Veszelka, Szilvia},
	doi = {10.1016/j.ejps.2018.07.042},
	journal-iso = {EUR J PHARM SCI},
	journal = {EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES},
	volume = {123},
	unique-id = {3399566},
	issn = {0928-0987},
	abstract = {Nanoparticles targeting transporters of the blood-brain barrier (BBB) are promising candidates to increase the brain penetration of biopharmacons. Solute carriers (SLC) are expressed at high levels in brain endothelial cells and show a specific pattern at the BBB. The aim of our study was to test glutathione and ligands of SLC transporters as single or dual BBB targeting molecules for nanovesicles. High mRNA expression levels for hexose and neutral amino acid transporting SLCs were found in isolated rat brain microvessels and our rat primary cell based co-culture BBB model. Niosomes were derivatized with glutathione and SLC ligands glucopyranose and alanine. Serum albumin complexed with Evans blue (67kDa), which has a very low BBB penetration, was selected as a cargo. The presence of targeting ligands on niosomes, especially dual labeling, increased the uptake of the cargo molecule in cultured brain endothelial cells. This cellular uptake was temperature dependent and could be decreased with a metabolic inhibitor and endocytosis blockers filipin and cytochalasin D. Making the negative surface charge of brain endothelial cells more positive with a cationic lipid or digesting the glycocalyx with neuraminidase elevated the uptake of the cargo after treatment with targeted nanocarriers. Treatment with niosomes increased plasma membrane fluidity, suggesting the fusion of nanovesicles with endothelial cell membranes. Targeting ligands elevated the permeability of the cargo across the BBB in the culture model and in mice, and dual-ligand decoration of niosomes was more effective than single ligand labeling. Our data indicate that dual labeling with ligands of multiple SLC transporters can potentially be exploited for BBB targeting of nanoparticles.},
	year = {2018},
	eissn = {1879-0720},
	pages = {228-240},
	orcid-numbers = {Kóta, Zoltán/0000-0003-2420-8773; Kupihár, Zoltán/0000-0001-5499-7617; Kéri, Albert/0000-0001-7663-5422; Galbács, Gábor/0000-0002-1799-5329; Fülöp, Lívia/0000-0002-8010-0129; Czirjákné Csete, Mária/0000-0002-3755-714X; Páli, Tibor/0000-0003-1649-1097; Rákhely, Gábor/0000-0003-2557-3641; Révész, Piroska/0000-0002-5336-6052; Deli, Mária Anna/0000-0001-6084-6524}
}

@article{MTMT:3358182,
	title = {Examination of the role of mitochondrial morphology and function in the cardioprotective effect of sodium nitrite administered 24 h before Ischemia/reperfusion injury},
	url = {https://m2.mtmt.hu/api/publication/3358182},
	author = {Demeter-Haludka, Vivien and Kovács, Mária and Petrus, A and Patai, Roland and Muntean, DM and Siklós, László and Végh, Ágnes},
	doi = {10.3389/fphar.2018.00286},
	journal-iso = {FRONT PHARMACOL},
	journal = {FRONTIERS IN PHARMACOLOGY},
	volume = {9},
	unique-id = {3358182},
	abstract = {Background: We have previous evidence that in anesthetized dogs the inorganic sodium nitrite protects against the severe ventricular arrhythmias, resulting from coronary artery occlusion and reperfusion, when administered 24 h before. The present study aimed to examine, whether in this effect changes in mitochondrial morphology and function would play a role. Methods: Thirty dogs were infused intravenously either with saline (n = 15) or sodium nitrite (0.2 μmol/kg/min; n = 15) for 20 min, and 24 h later, 10 dogs from each group were subjected to a 25 min period of occlusion and then reperfusion of the left anterior descending coronary artery. The severity of ischaemia and ventricular arrhythmias were examined in situ. Left ventricular tissue samples were collected either before the occlusion (5 saline and 5 nitrite treated dogs) or, in dogs subjected to occlusion, 2 min after reperfusion. Changes in mitochondrial morphology, in complex I and complex II-dependent oxidative phosphorylation (OXPHOS), in ATP, superoxide, and peroxynitrite productions were determined. Results: The administration of sodium nitrite 24 h before ischemia/reperfusion significantly attenuated the severity of ischaemia, and markedly reduced the number and incidence of ventricular arrhythmias. Nitrite also attenuated the ischaemia and reperfusion (I/R)-induced structural alterations, such as reductions in mitochondrial area, perimeter, and Feret diameter, as well as the increase in mitochondrial roundness. The administration of nitrite, however, enhanced the I/R-induced reduction in the mitochondrial respiratory parameters; compared to the controls, 24 h after the infusion of nitrite, there were further significant decreases, e.g., in the complex I-dependent OXPHOS (by -20 vs. -53%), respiratory control ratio (by -14 vs. -61%) and in the P/E control coupling ratio (by 2 vs. -36%). Nitrite also significantly reduced the I/R-induced generation of superoxide, without substantially influencing the ATP production. Conclusions: The results suggest that sodium nitrite may have an effect on the mitochondria; it preserves the mitochondrial structure and modifies the mitochondrial function, when administered 24 h prior to I/R. We propose that nitrite affects primary the phosphorylation system (indicated by the decreased P/E ratio), and the reduction in superoxide production would result from the subsequent suppression of the ROS producing complexes; an effect which may certainly contribute to the antiarrhythmic effect of nitrite. © 2018 Demeter-Haludka, Kovács, Petrus, Patai, Muntean, Siklós and Végh.},
	keywords = {Arrhythmia; MITOCHONDRIAL RESPIRATION; Ischaemia/reperfusion; cardioprotection; sodium nitrite; Mitochondrial structure},
	year = {2018},
	eissn = {1663-9812}
}