TY  - JOUR
AU  - Kalweit, Alexander Nikolai
AU  - Yang, Honghong
AU  - Colitti-Klausnitzer, Jens
AU  - Fülöp, Lívia
AU  - Bozsó, Zsolt
AU  - Penke, Botond
AU  - Manahan-Vaughan, Denise
TI  - Acute intracerebral treatment with amyloid-beta (1-42) alters the profile of neuronal oscillations that accompany LTP induction and results in impaired LTP in freely behaving rats
JF  - FRONTIERS IN BEHAVIORAL NEUROSCIENCE
J2  - FRONT BEHAV NEUROSCI
VL  - 9
PY  - 2015
PG  - 16
SN  - 1662-5153
DO  - 10.3389/fnbeh.2015.00103
UR  - https://m2.mtmt.hu/api/publication/2940235
ID  - 2940235
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Varga, Edina
AU  - Juhász, Gábor
AU  - Bozsó, Zsolt
AU  - Penke, Botond
AU  - Fülöp, Lívia
AU  - Szegedi, Viktor
TI  - Amyloid-β1-42 disrupts synaptic plasticity by altering glutamate recycling at the synapse
JF  - JOURNAL OF ALZHEIMER'S DISEASE
J2  - J ALZHEIMERS DIS
VL  - 45
PY  - 2015
IS  - 2
SP  - 449
EP  - 456
PG  - 8
SN  - 1387-2877
DO  - 10.3233/JAD-142367
UR  - https://m2.mtmt.hu/api/publication/2812783
ID  - 2812783
AB  - Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorders characterized by neuritic plaques containing amyloid-beta peptide (Abeta) and neurofibrillary tangles. Evidence has been reported that Abeta1-42 plays an essential pathogenic role in decreased spine density, impairment of synaptic plasticity, and neuronal loss with disruption of memory-related synapse function, all associated with AD. Experimentally, Abeta1-42 oligomers perturb hippocampal long-term potentiation (LTP), an electrophysiological correlate of learning and memory. Abeta was also reported to perturb synaptic glutamate (Glu)-recycling by inhibiting excitatory-amino-acid-transporters. Elevated level of extracellular Glu leads to activation of perisynaptic receptors, including NR2B subunit containing NMDARs. These receptors were shown to induce impaired LTP and enhanced long-term depression and proapoptotic pathways, all central features of AD. In the present study, we investigated the role of Glu-recycling on Abeta1-42-induced LTP deficit in the CA1. We found that Abeta-induced LTP damage, which was mimicked by the Glu-reuptake inhibitor TBOA, could be rescued by blocking the NR2B subunit of NMDA receptors. Furthermore, decreasing the level of extracellular Glu using a Glu scavenger also restores TBOA or Abeta induces LTP damage. Overall, these results suggest that reducing ambient Glu in the brain can be protective against Abeta-induced synaptic disruption.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Varga, Edina
AU  - Juhász, Gábor
AU  - Bozsó, Zsolt
AU  - Penke, Botond
AU  - Fülöp, Lívia
AU  - Szegedi, Viktor
TI  - Abeta(1-42) Enhances Neuronal Excitability in the CA1 via NR2B Subunit-Containing NMDA Receptors
JF  - NEURAL PLASTICITY
J2  - NEURAL PLAST
VL  - 2014
PY  - 2014
PG  - 12
SN  - 2090-5904
DO  - 10.1155/2014/584314
UR  - https://m2.mtmt.hu/api/publication/2755870
ID  - 2755870
AB  - 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.
LA  - English
DB  - MTMT
ER  -