NMDA receptor dependent LTP at CA3 CA1 synapses is not associated with 12 LO action as discussed above. Ergo, other molecular mechanisms underlying the result of baicalein has to be investigated. The PI3K pathway has been classically buy BMN 673 mixed up in regulation of cell growth, success, expansion. In addition to its well established function in neuronal survival and differentiation, PI3K can be essential in synaptic plasticity and learning and memory. For example, it has been shown that activation of PI3K is required for the expression of LTP in the hippocampal CA1 region. PI3K may give rise to the regulation of memory formation and NMDA receptor dependent LTP by facilitating the insertion of AMPA receptors in to the postsynaptic membrane. In our previous studies, baicalein Cellular differentiation attenuated learning and memory deficits and protected neurons against ischaemic damage by activating the PI3K/Akt pathway in rats. Furthermore, other flavonoids such as the citrus flavanone hesperetin activate the pathway in neurons and flavonoids are known to activate Akt phosphorylation at Ser473 in a dose dependent fashion. In accordance with a previous statement, we found here that the PI3K inhibitors LY294002 and wortmannin decreased the magnitude of LTP and PI3K inhibitors totally blocked baicalein facilitated LTP, supporting an involvement of PI3K signalling in baicalein facilitated LTP. We indirectly checked the activation of PI3K by measuring the phosphorylation of its downstream target Akt at Ser473 using Western blot analysis, to ascertain whether up regulation of PI3K activity is responsible for the enhancement of LTP by baicalein treatment. We found that HFS induction was related to an increase in the phosphorylation of Akt Anacetrapib molecular weight mw at Ser473 timedependently. Moreover, increased phosphorylation of Akt was further increased by baicalein therapy in a bell-shaped dose-response manner that peaked at 1 mM, indicating that the service of the PI3K pathway by baicalein in hippocampal slices following HFS can take into account its enhancement of LTP. cAMP response element binding protein is a transcription factor for several genes related to synaptic plasticity and memory. More over, sturdy CREB phosphorylation was found in hippocampus in response to both LTP causing activation and memory training duties. Numerous signalling pathways have now been connected to CREB activation in the induction of long lasting changes in synaptic plasticity and memory, including the ERK and PI3K pathways. We discovered that CREB phosphorylation was significantly increased in the CA1 region of baicalein handled pieces after HFS. More over, baicalein treatment selectively increased the phosphorylation of CREB in the CA1 area of hippocampus, although not in prefrontal cortex, after fear conditioning training.