Noradrenaline regulates the expression of CPEB3, an RNA binding protein in the cerebellum

SONIAT A; BENDER C; LIU SQ

NEW ORLEANS

Jornada; Summer student meeting; 2013

LSUHSC

The processing of information in the brain is based on the actions of excitatory and inhibitory neurons. Excitatory neurons release glutamate neurotransmitter that binds to glutamate receptors. This leads to excitation of their target neurons. The AMPA type glutamate receptor is crucial for conducting this form of excitatory transmission. In cerebellar stellate cells, the GluR2 subunit of the AMPA receptor (AMPAR) has been implicated in associative learning and memory. One single fear-stimulus can promote GluR2 transcription and trigger an increase in AMPARs that contain GluR2 subunits.However whether a stress hormone, noradrenaline, regulates GluR2 protein synthesis is not known.  CPEB3 (Cytoplasmic Polyadenylation Element Binding protein 3) suppresses GluR2 synthesis and is associated with learning and memory in humans. We have previously shown that incubation of cultured cerebellar neurons with noradrenaline increased the CPEB3 level in stellate cells. We therefore identified which type of adrenergic receptor mediates the noradrenaline-induced change in CPEB3 expression.  We used two experimental approaches. First we tested whether prazosin (an α-receptor antagonist) and propranolol (a β-receptor antagonist) prevented the noradrenaline-induced increase in CPEB3 expression. Second, we determined whether activation of α-receptors by phenylephrine or β-receptors by isopropanol is sufficient to elevate CPEB3 expression in stellate cells. By identifying the adrenergic receptors that regulate CPEB3 expression, we can further determine the mechanism underlying the stress-induced change in synaptic AMPARs. This will aid in our understating of how stress alters synaptic transmission in the CNS. The data from two cultures of neuronal cells indicated that alpha adrenergic-receptors mediate the NE-induced increase in CPEB3 expression.