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1.
Nat Commun ; 5: 4563, 2014 Aug 01.
Article in English | MEDLINE | ID: mdl-25081057

ABSTRACT

Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized by the presence of brain malformations, the cortical tubers that are thought to contribute to the generation of pharmacoresistant epilepsy. Here we report that tuberless heterozygote Tsc1(+/-) mice show functional upregulation of cortical GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) in an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (

Subject(s)
Anticonvulsants/pharmacology , Epilepsy/drug therapy , Pyrazoles/pharmacology , Quinolones/pharmacology , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , TOR Serine-Threonine Kinases/genetics , Tuberous Sclerosis/drug therapy , Tumor Suppressor Proteins/genetics , Action Potentials/drug effects , Animals , Disease Models, Animal , Electroencephalography , Epilepsy/genetics , Epilepsy/metabolism , Epilepsy/pathology , Gene Expression Regulation , Heterozygote , Humans , Male , Mice , Mice, Transgenic , Microtomy , Neocortex/drug effects , Neocortex/metabolism , Neocortex/pathology , Patch-Clamp Techniques , Receptors, N-Methyl-D-Aspartate/genetics , Receptors, N-Methyl-D-Aspartate/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Tissue Culture Techniques , Tuberous Sclerosis/genetics , Tuberous Sclerosis/metabolism , Tuberous Sclerosis/pathology , Tuberous Sclerosis Complex 1 Protein , Tumor Suppressor Proteins/deficiency
2.
Fiziol Zh (1994) ; 52(4): 9-12, 2006.
Article in Ukrainian | MEDLINE | ID: mdl-16958210

ABSTRACT

The modulatory effect of endogenous diadenosine polyphosphates on synaptic transmission in the rat hippocampal slices has been re-examined with a non-hydrolysable Ap4A analogue diadenosine-5',5'>>-P1,P4-[beta,gamma-methylene]tetraphosphate (AppCH2ppA). We have shown that AppCH2ppA at low micromolar concentrations induce inhibition of orthodromically evoked population spikes, without affecting of excitatory postsynaptic currents and antidromic spikes recorded in the CA1 zone of hippocampus. Such a spatially selective neuronal inhibition may influence dendritic electrogenesis in pyramidal neurons and consequently mediate control of neuronal network activity in hippocampus.


Subject(s)
Dinucleoside Phosphates/physiology , Hippocampus/physiology , Synaptic Transmission/physiology , Action Potentials/physiology , Animals , Dinucleoside Phosphates/pharmacology , Electric Stimulation , Electrodes , Hippocampus/drug effects , In Vitro Techniques , Patch-Clamp Techniques , Pyramidal Cells/drug effects , Pyramidal Cells/physiology , Rats , Rats, Wistar , Synaptic Transmission/drug effects
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