Abstract
A hydroethanolic extract (20% V/V) from Herba Sideritis scardica has been recognized to positively influence cognition. The present investigation aimed at the question if this extract would be able to modify intra-hippocampal communication after oral administration of 100 mg/kg daily for one week. The glutamatergic synapse between Schaffer Collaterals and pyramidal cells can be tested by electric stimulation using single pulses or theta burst stimulation. The resulting population spike is modulated by compounds acting at the central nervous system or other preparations directly or as ex vivo approach. In this case the effect of the special extract was tested in vitro the next day after repetitive in vitro administration. Conventional recording technique in the in vitro hippocampus slice revealed an increase of the population spike in the presence of single stimuli and theta burst stimuli resulting in increased long-term potentiation. This effect was tried to modulate by several glutamate receptor antagonists, among them compounds targeting at the ionic NMDA receptor (CGS19755), AMPA receptor (NBQX), Kainate receptor (UBP301) and targeting at three metabotropic glutamate receptors (mGluR I (YM298198), mGluRII ((RS)-APICA)) and mGluRIII (MSOP). Only NBQX was able to prevent the action of the Sideritis scardica extract. Since the AMPA receptor has been related to cognition in several reports in the literature, it is concluded from this result that the positive action of Sideritis scardica extract on brain function involves a modulation of AMPA receptor dependent neurotransmission.
Highlights
The hippocampal slice preparation is a validated model for direct analysis of interaction of substances with living neuronal tissue [1]
This effect was tried to modulate by several glutamate receptor antagonists, among them compounds targeting at the ionic NMDA receptor (CGS19755), amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (NBQX), Kainate receptor (UBP301) and targeting at three metabotropic glutamate receptors (mGluR I (YM298198), mGluRII ((RS)APICA)) and mGluRIII (MSOP)
During the second part of the investigation it was tried to reverse the modulation by 6 different receptor antagonists interacting with glutamatergic transmission
Summary
The hippocampal slice preparation is a validated model for direct analysis of interaction of substances with living neuronal tissue [1]. Due to the preservation of the three dimensional structure of the hippocampal tissue, substance effects on the excitability of pyramidal cells can be studied in a unique manner. The stimulation of Schaffer Collaterals leads to release of glutamate resulting in excitation of the postsynaptic pyramidal cells. The result of the electrical stimulation can be recorded as so-called population spike (pop-spike). The amplitude of the resulting population spike represents the number of recruited pyramidal cells. The advantage of the model consists in the possibility of recording in vitro during 8 hours and to modify the excitability of the system in order to create pathophysiological conditions. The model of hippocampal pyramidal cell activity reflects the effects of therapeutic interventions by increase or decrease of the amplitude of the population spike. It provides an excellent model to characterize the action of a new therapeutic principle with respect to changes of brain function under strictly controlled laboratory conditions
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