The epilepsies are a heterogenous group of symptom complexes, whose common features is the recurrence of seizures. There is no certain therapy for epilepsy. In order to promote new advances for the prevention of epilepsy the molecular mechanism of epileptic activities should be clarified.
In the present study the goal is to obtain information for molecular mechanism of epilepsy. To achieve this, molecular alterations from pentylenetetrazol (PTZ)-induced epileptic activities on rat brain tissue and cell membranes were investigated by Fourier Transform Infrared (FTIR) spectroscopy, Fourier Transform Infrared Microscopy and Atomic Force Microscopy (AFM). Moreover, the therapeutic role of an antiepileptic agent vigabatrin (VGB) on epileptic rat brain membranes were examined at molecular level.
For better understanding of the action mechanism of PTZ and an antiepileptic drug VGB in cell membranes we firstly studied at model level using multilamellar liposomes (MLVs). We investigated PTZ-DPPC MLVs interactions
in terms of lipid phase behavior, order and dynamics and nature of hydrogen bonding around its polar part, using Fourier Transform Infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), Electronspin Resonans Spectroscopy (ESR) and Steady State Fluorescence Spectroscopy. According to our data, PTZ has no ability to interact with membrane lipids. On the other hand, the results of VGB-DPPC interactions showed that VGB strongly interact with the head group and/or the region near the head of membrane phospholipids.
The molecular investigation of PTZ-induced epileptic activities revealed that PTZ-induced seizures cause a decrease in the lipid and protein content, membrane fluidity and glycogen level. They stimulate alterations in membrane packing and the secondary structure of proteins as well as lipid peroxidation. In addition, our results show the transcription of early genes following high dose PTZ administration. All these molecular alterations variatins are only resulted from the consequences of epileptic activities not from convulsant agent PTZ itself.
The important finding is that, VGB restored some of the alterations by PTZ-induced epileptic activities on brain cell membrane. For instance, it restored membrane fluidity, lipid peroxidation, phospholipid degradation and changes in membrane organization. However, it was found that VGB has no significant effects on the changes in protein secondary structure.
| Identifer | oai:union.ndltd.org:METU/oai:etd.lib.metu.edu.tr:http://etd.lib.metu.edu.tr/upload/3/12611100/index.pdf |
| Date | 01 August 2009 |
| Creators | Turker Gorgulu, Sevgi |
| Contributors | Severcan, Feride |
| Publisher | METU |
| Source Sets | Middle East Technical Univ. |
| Language | English |
| Detected Language | English |
| Type | Ph.D. Thesis |
| Format | text/pdf |
| Rights | Access forbidden for 1 year |
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