Mystixin-7 Peptide Protects Ionotropic Glutamatergic Mechanisms against Glutamate-Induced Excitotoxicity In Vitro

Figure 1

The model of glutamate excitotoxicity in the olfactory cortex slices. (a) Effects application of L-glutamate in toxic concentration (20 mM) on profiles FPs. Representative FPs were recorded in time points 1, 2, and 3, respectively, as indicated in (b). FPs are integral averaging potentials generated by neurons in slices processing by special computer program at four independent experiments performed in triplicate in different slices ( per treatment condition). The dotted line indicates isoline. Arrows indicate AMPA and NMDA components of the EPSP. The vertical arrows from isoline to the peaks of the AMPA and NMDA EPSP show as conducted the measurements of their amplitudes. The captions about the conditions exposures to slices (legend beneath (a)) indicate time points of the registration FPs, corresponding to the points in (b), namely, (1) “Cntr,” (2) “Glu, 20 min,” and (3) “Wsh, 30 min.” Calibration as is indicated. At the FPs registration, the electronic device (Pavlov Institute of Physiology, RAS) for artefact-rejection was used. (b) Change of the AMPA and NMDA EPSP amplitudes at imitation glutamate excitotoxicity obtained at application of L-glutamate (20 mM) on the olfactory cortex slices. The -axis—“Ctrl”: control values of AMPA and NMDA EPSP (without the glutamate), 15 min; thick arrow and “Wsh” indicate washout, 30 min. The dotted line indicates the control level corresponding to 100%. The duration application of L-glutamate on the slices for modeling of the glutamate excitotoxicity was 60 min. The results are expressed as percentage of control condition and represent means ± SEM of 4 independent experiments performed in triplicate in different slices and analyzed statistically by -test, Wilcoxon-Mann-Whitney matched pairs signed-rank test. , significantly different from control. , number of slices per time point performed in the repeated at least four independent experiments. At the FPs registration, the electronic device (Pavlov Institute of Physiology, RAS) for artefact-rejection was used. Note that L-glutamate induces the most significant hyperactivity of NMDARs with a maximum value at 20 min. Then the amplitudes of these components FPs progressively decreased and to 60th min were irreversibly blocked. The increase in AMPARs activity at action agonist was smaller, but with longer duration than NMDARs and after 40 min there was a decrease and irreversible blockade of these receptors’ activity.

(a)

(b)