Amygdala amino acid and monoamine levels in genetically Fast and Slow kindling rat strains during massed amygdala kindling: a microdialysis study

We investigated the neurochemistry of epileptic seizures in rats selectively bred to be seizure-prone (Fast) vs. seizure-resistant (Slow) to amygdala kindling. Microdialysis was used to measure levels of amino acids [glutamate, aspartate and gamma-aminobutyric acid (GABA)] and monoamines (noradrenaline, dopamine and serotonin) during \u27massed\u27 stimulation (MS) (every 6 min) of the ipsilateral amygdala for a total of 40 stimulation trials. Behavioral seizure profiles together with their afterdischarge thresholds (ADTs) and associated durations were assessed during the procedure, and subsequently were redetermined 1, 7 and 14 days later. Then normal \u27daily\u27 kindling commenced and continued until the animal reached the fully kindled state. During MS, several generalized seizures were triggered in Fast rats that were associated with long afterdischarge (AD) durations and intermittent periods of elevated thresholds, but in Slow rats, most stimulations were associated with stable ADTs and short ADs. Progressively increasing extracellular glutamate and decreasing GABA was observed in Fast rats during the MS, whereas Slow rats showed levels similar to baseline values. Levels of noradrenaline and dopamine, but not of serotonin, were also increased in both strains throughout the MS treatment. In Fast rats, a dramatic lengthening of AD durations occurred 7 and 14 days following MS, as well as subsequent strong positive transfer to daily kindling, all of which were not seen in Slow rats. Together, these results show that repeated, closely spaced stimulations of the amygdala can differentially alter excitatory and/or inhibitory transmitter levels in a seizure network, and that sensitivity to this manipulation is genetically determined

Peptide Foldamers: from Spectroscopic Studies to Applications.

Peptide foldamers are synthetic oligopeptides which attain a few, specific, constrained conformations in solution. Here, we review our contributions to the study of the structural features of several foldamers, comprising C\u3b1-tetrasubstituted aminoacids, by spectroscopic techniques and, in particular, by a combined approach employing time-resolved energy transfer (FRET) experiments and molecular modeling to determine interprobe distances and orientations. Our data show that, for rigid systems, the commonly used assumption of random orientation of donor and acceptor is unjustified, and that in these cases a correct evaluation of the orientation factor is mandatory for meaningful structural determinations. Finally, we illustrate some applications of peptide foldamers in studies on the kinetics of protein folding and on the realization of peptide-based molecular devices.