@article{MTMT:2755870, title = {Abeta(1-42) Enhances Neuronal Excitability in the CA1 via NR2B Subunit-Containing NMDA Receptors}, url = {https://m2.mtmt.hu/api/publication/2755870}, author = {Varga, Edina and Juhász, Gábor and Bozsó, Zsolt and Penke, Botond and Fülöp, Lívia and Szegedi, Viktor}, doi = {10.1155/2014/584314}, journal-iso = {NEURAL PLAST}, journal = {NEURAL PLASTICITY}, volume = {2014}, unique-id = {2755870}, issn = {2090-5904}, abstract = {Neuronal hyperexcitability is a phenomenon associated with early Alzheimer's disease. The underlying mechanism is considered to involve excessive activation of glutamate receptors; however, the exact molecular pathway remains to be determined. Extracellular recording from the CA1 of hippocampal slices is a long-standing standard for a range of studies both in basic research and in neuropharmacology. Evoked field potentials (fEPSPs) are regarded as the input, while spiking rate is regarded as the output of the neuronal network; however, the relationship between these two phenomena is not fully clear. We investigated the relationship between spontaneous spiking and evoked fEPSPs using mouse hippocampal slices. Blocking AMPA receptors (AMPARs) with CNQX abolished fEPSPs, but left firing rate unchanged. NMDA receptor (NMDAR) blockade with MK801 decreased neuronal spiking dose dependently without altering fEPSPs. Activating NMDARs by small concentration of NMDA induced a trend of increased firing. These results suggest that fEPSPs are mediated by synaptic activation of AMPARs, while spontaneous firing is regulated by the activation of extrasynaptic NMDARs. Synaptotoxic Abeta(1-42) increased firing activity without modifying evoked fEPSPs. This hyperexcitation was prevented by ifenprodil, an antagonist of the NR2B NMDARs. Overall, these results suggest that Abeta(1-42) induced neuronal overactivity is not dependent on AMPARs but requires NR2B.}, year = {2014}, eissn = {1687-5443}, orcid-numbers = {Bozsó, Zsolt/0000-0002-5713-3096; Penke, Botond/0000-0003-0938-0567; Fülöp, Lívia/0000-0002-8010-0129; Szegedi, Viktor/0000-0003-4191-379X} } @article{MTMT:1412694, title = {Different electrophysiological actions of 24- and 72-hour aggregated amyloid-beta oligomers on hippocampal field population spike in both anesthetized and awake rats}, url = {https://m2.mtmt.hu/api/publication/1412694}, author = {Orbán, Gergely and Völgyi, Katalin and Juhász, Gábor Dénes and Penke, Botond and Kékesi, Adrienna Katalin and Kardos, József and Czurkó, András}, doi = {10.1016/j.brainres.2010.07.061}, journal-iso = {BRAIN RES}, journal = {BRAIN RESEARCH}, volume = {1354}, unique-id = {1412694}, issn = {0006-8993}, abstract = {Diffusible oligomeric assemblies of the amyloid β-protein (Aβ) could be the primary factor in the pathogenic pathway leading to Alzheimer's disease (AD). Converging lines of evidence support the notion that AD begins with subtle alterations in synaptic efficacy, prior to the occurrence of extensive neuronal degeneration. Recently, however, a shared or overlapping pathogenesis for AD and epileptic seizures occurred as aberrant neuronal hyperexcitability, as well as nonconvulsive seizure activity were found in several different APP transgenic mouse lines. This generated a renewed attention to the well-known comorbidity of AD and epilepsy and interest in how Aβ oligomers influence neuronal excitability. In this study therefore, we investigated the effect of various in vitro-aged Aβ(1-42) oligomer solutions on the perforant pathway-evoked field potentials in the ventral hippocampal dentate gyrus in vivo. Firstly, Aβ oligomer solutions (1 μl, 200 μM) which had been aggregated in vitro for 0, 24 or 72 h were injected into the hippocampus of urethane-anesthetized rats, in parallel with in vitro physico-chemical characterization of Aβ oligomerization (atomic force microscopy, thioflavin-T fluorescence). We found a marked increase of hippocampal population spike (pSpike) after injection of the 24-h Aβ oligomer solution and a decrease of the pSpike amplitude after injection of the 72-h Aβ oligomer. Since urethane anesthesia affects the properties of hippocampal evoked potentials, we repeated the injection of these two Aβ oligomer solutions in awake, freely moving animals. Evoked responses to perforant pathway stimulation revealed a 70% increase of pSpike amplitude 50 min after the 24-h Aβ oligomer injection and a 55% decrease after the 72-h Aβ oligomer injection. Field potentials, that reflect synaptic potentials, were not affected by the Aβ injection. These results demonstrate that oligomeric Aβ aggregates elicit opposite electrophysiological effects on neuronal excitability which depend on their degree of oligomerization. © 2010 Elsevier B.V. All rights reserved.}, keywords = {Male; hippocampus; ARTICLE; Electrophysiology; priority journal; controlled study; Rattus; nonhuman; animal experiment; Animalia; wakefulness; nerve cell; dentate gyrus; atomic force microscopy; Alzheimer's disease; neuroprotection; amyloid; Mus musculus; perforant nerve tract; oligomerization; electric potential; amyloid beta protein[1-42]; Oligomer; Excitability; rat}, year = {2010}, eissn = {1872-6240}, pages = {227-235}, orcid-numbers = {Juhász, Gábor Dénes/0000-0002-0849-6931; Penke, Botond/0000-0003-0938-0567; Kékesi, Adrienna Katalin/0000-0003-3042-4878; Kardos, József/0000-0002-2135-2932; Czurkó, András/0000-0002-1985-7296} } @article{MTMT:246935, title = {Amyloid beta-Induced Neuronal Hyperexcitability Triggers Progressive Epilepsy}, url = {https://m2.mtmt.hu/api/publication/246935}, author = {Minkeviciene, R and Rheims, S and Dobszay, Márton Benedek and Zilberter, M and Hartikainen, J and Fülöp, Lívia and Penke, Botond and Zilberter, Y and Harkany, T and Pitkanen, A and Tanila, H}, doi = {10.1523/JNEUROSCI.5215-08.2009}, journal-iso = {J NEUROSCI}, journal = {JOURNAL OF NEUROSCIENCE}, volume = {29}, unique-id = {246935}, issn = {0270-6474}, abstract = {Alzheimer's disease is associated with an increased risk of unprovoked seizures. However, the underlying mechanisms of seizure induction remain elusive. Here, we performed video-EEG recordings in mice carrying mutant human APPswe and PS1dE9 genes (APdE9 mice) and their wild-type littermates to determine the prevalence of unprovoked seizures. In two recording episodes at the onset of amyloid beta (A beta) pathogenesis (3 and 4.5 months of age), at least one unprovoked seizure was detected in 65% of APdE9 mice, of which 46% had multiple seizures and 38% had a generalized seizure. None of the wild-type mice had seizures. In a subset of APdE9 mice, seizure phenotype was associated with a loss of calbindin-D28k immunoreactivity in dentate granular cells and ectopic expression of neuropeptide Y in mossy fibers. In APdE9 mice, persistently decreased resting membrane potential in neocortical layer 2/3 pyramidal cells and dentate granule cells underpinned increased network excitability as identified by patch-clamp electrophysiology. At stimulus strengths evoking single-component EPSPs in wild-type littermates, APdE9 mice exhibited decreased action potential threshold and burst firing of pyramidal cells. Bath application (1h) of A beta 1-42 or A beta 25-35 (proto-) fibrils but not oligomers induced significant membrane depolarization of pyramidal cells and increased the activity of excitatory cell populations as measured by extracellular field recordings in the juvenile rodent brain, confirming the pathogenic significance of bath-applied A beta(proto-) fibrils. Overall, these data identify fibrillar A beta as a pathogenic entity powerfully altering neuronal membrane properties such that hyperexcitability of pyramidal cells culminates in epileptiform activity.}, year = {2009}, eissn = {1529-2401}, pages = {3453-3462}, orcid-numbers = {Fülöp, Lívia/0000-0002-8010-0129; Penke, Botond/0000-0003-0938-0567} } @article{MTMT:247687, title = {Enhancement of NMDA responses by ß-amyloid peptides in the hippocampus in vivo}, url = {https://m2.mtmt.hu/api/publication/247687}, author = {Molnar, Z and Soós, Katalin and Lengyel, Imre and Penke, Botond and Szegedi, Viktor and Budai, D}, doi = {10.1097/01.wnr.0000134471.06244.d2}, journal-iso = {NEUROREPORT}, journal = {NEUROREPORT}, volume = {15}, unique-id = {247687}, issn = {0959-4965}, year = {2004}, eissn = {1473-558X}, pages = {1649-1652}, orcid-numbers = {Penke, Botond/0000-0003-0938-0567; Szegedi, Viktor/0000-0003-4191-379X} } @article{MTMT:109099, title = {β-Amyloid neurotoxicity is mediated by a glutamate-triggered excitotoxic cascade in rat nucleus basalis}, url = {https://m2.mtmt.hu/api/publication/109099}, author = {Harkany, T and Ábrahám, István and Timmerman, W and Laskay, Gábor and Tóth, B and Sasvári, M and Kónya, C and Sebens, JB and Korf, J and Nyakas, Csaba and Zarándi, Márta and Soós, Katalin and Penke, Botond and Luiten, PGM}, doi = {10.1046/j.1460-9568.2000.00164.x}, journal-iso = {EUR J NEUROSCI}, journal = {EUROPEAN JOURNAL OF NEUROSCIENCE}, volume = {12}, unique-id = {109099}, issn = {0953-816X}, year = {2000}, eissn = {1460-9568}, pages = {2735-2745}, orcid-numbers = {Nyakas, Csaba/0000-0003-3756-0186; Zarándi, Márta/0000-0002-2136-2946; Penke, Botond/0000-0003-0938-0567} }