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Intracerebroventricular antisense to inositol monophosphatase-1 reduces enzyme activity but does not affect
Alon Shamir1, Galit Shaltiel, Galila Agam
1Stanley Foundation Research Center and Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Inositol monophosphatase (IMPase) inhibition is a hypothesized mechanism of action of lithium (Li). To test this hypothesis, the authors used the approach of antisense administration. Three days of an intracerebroventricular (icv) administration of 5 microg/20 microl 3'-phosphorothioated IMPA-1 antisense oligonucleotide sequence resulted in 20% reduction of rat periventricular IMPase activity. Li potentiates pilocarpine-induced seizures, because inhibition of IMPase leads to reduction in brain inositol levels. However, antisense-induced reduction in IMPase activity was not followed by seizures induced by subconvulsive pilocarpine doses.
Inositol monophosphatase (IMPase) inhibition is a hypothesized mechanism of action of lithium (Li). To test this hypothesis, the authors used the approach of antisense administration. Three days of an intracerebroventricular (icv) administration of 5 microg/20 microl 3'-phosphorothioated IMPA-1 antisense oligonucleotide sequence resulted in 20% reduction of rat periventricular IMPase activity. Li potentiates pilocarpine-induced seizures, because inhibition of IMPase leads to reduction in brain inositol levels. However, antisense-induced reduction in IMPase activity was not followed by seizures induced by subconvulsive pilocarpine doses.