Epilepsy is one of the most devastating neurological diseases affecting about 1% of human population and despite significant
efforts there is no cure available. Occurrence of spontaneous seizures in epilepsy is preceded by numerous molecular and
structural pathophysiological reorganizations in the brain—a process called epileptogenesis. Treatment strategies targeting
this process may be efficient for preventing spontaneous recurrent seizures (SRS) in epilepsy, or for modification of disease
progression. Our laboratory has shown that Myo-inositol (MI) is one of the active components of water extract of plant
Aquilegia vulgaris (a plant used in oriental folk medicine as anti-epileptic and soporific medicinal). MI possess anti-seizure
properties on various pharmacological models of epilepsy. Moreover we have shown that MI post- treatment after Kainic acid
(KA) induced status epilepticus has compensatory long-term influence on different behavioral, biochemical and
morphological aspects of epiletogenesis and the frequency and duration of SRS are suppressed even after ceasing the
treatment. Biochemical changes after MI treatment, amongst many others include increased level of Sodium/MI transporter,
which indicates for increased uptake of MI.
Except MI there are two physiologically active inositol isomers, namely scyllo-Inositol (SCI) and D-chiro-inositol (DCI)
which are produced from MI by specific epimerases. Anti-convulsant activity of SCI was demonstrated in our laboratory
previously. It is possible that increased intracellular accumulation of MI leads to elevated levels of SCI or/and DCI which are
also responsible for anti-epileptogenic properties. There are no any data about the intracellular targets of either of these
inositols action. We do not know which of these inositols is more effective for the prevention/weakening of epileptogenesis.
The aims of the present project are; (i) identification of intracellular targets of MI, SCI and DCI action in hippocampal
cytoplasmic fraction. For this purpose we will apply cellular thermal shift assay in combination with 2-dimensional gelelectrophoresis; (ii) comparative study of MI, SCI and DCI effects on the process of epileptogenesis. The SRS frequencies and
duration will be evaluated in parallel with learning and memory efficiency. Also changes in identified inositol target protein
expression and modifications in molecular markers of epileptogenesis will be studied. Such a studies were never performed
before and it will bring the group of inositol isomers to the level of translational research.