Limbic progesterone receptor activity enhances neuronal excitability and seizures.

OBJECTIVE: Emerging evidence raises the possibility that progesterone receptor (PR) signaling may contribute to the reproductive hormone fluctuation-linked seizure precipitation, called catamenial epilepsy. Therefore, we studied PR isoform expression in limbic regions involved in temporal lobe epilepsy and the effect of PR activation on neuronal activity and seizures. METHODS: We evaluated PR expression in the limbic regions, entorhinal cortex (EC), hippocampus, and amygdala in female rats using quantitative real-time polymerase chain reaction (qRT-PCR). A selective agonist, Nestorone (16-methylene-17 alpha-acetoxy-19-nor-pregn-4-ene-3,20-dione) activated PRs, and the effect on excitability and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated synaptic transmission of EC neurons was studied using electrophysiology. Finally, we assessed PR regulation of epileptic seizures and status epilepticus (SE) induced by lithium-pilocarpine in female rats with the global deletion of PRs (PR knockout; PRKO) using video electroencephalography (-EEG). RESULTS: Limbic regions EC, hippocampus, and amygdala robustly expressed PR messenger RNA (mRNA). Nestorone (16-methylene-17 alpha-acetoxy-19-nor-pregn-4-ene-3,20-dione) treatment reduced the action potential threshold of layer II/III EC neurons and increased the frequency of AMPA receptor-mediated synaptic currents of ovariectomized and estrogen-primed female rats. Female rats lacking PRs (PRKO) experienced a shorter duration, less intense, and less fatal SE than wild-type (WT) animals. Furthermore, Nestorone treatment caused seizure exacerbation in the WT epileptic animals, but not in the PRKO epileptic animals. SIGNIFICANCE: Activation of PRs expressed in the EC and hippocampus increased neuronal excitability and worsened seizures. These receptors may play a role in catamenial epilepsy.

Hydrolysis of Schiff bases with phenyl-ethynyl-phenyl system: The importance for biological and physicochemical studies.

A series of new Schiff bases containing the phenyl-ethynyl-phenyl system was synthesized and their thermal stability, photophysical and electrochemical properties were investigated. Moreover, DFT calculations were performed to obtain the optimized ground-state geometry and distribution of the HOMO and LUMO levels as well as IR spectra of the prepared compounds. It was found that, the photoluminescence of synthesized imines was negligible in all investigated organic solvents except for the PBS/ACN mixture. As was proved in further studies, this phenomenon was related to the partial hydrolysis of imines, which is the source of the fluorogenic aldehyde causing the aggreggacion incrased-emision effect. In further research, due to the susceptibility of the azomethines to partial hydrolysis, the biological activity of 2-{(E)-[4-(phenylethynyl) phenyl]imino}phenol (1b), substrate (2-aminophenol) and Cu(II)-1b complex was analyzed. The biological tests showed, that 1b (as example of imine resveratrol analogue), demonstrated its increased cytostatic activity in prostate cancer cellular system. It was proved that the non-hydrolyzed imine was crucial for the cytotoxic effect. This activity could be ascribed to its Cu(II) complexing capability as showed in our previous research.