Abstract The molecular mechanisms underlying circuit re-wiring in the mature brain remains ill-defined.An eloquent example of adult circuit remodelling is the hippocampal mossy fiber (MF) sprouting found in diseases such as temporal lobe epilepsy.The molecular determinants underlying this retrograde re-wiring remain unclear.
This may involve signaling system(s) controlling axon specification/growth during neurodevelopment reactivated during epileptogenesis.Since adenosine A2A receptors (A2AR) control axon formation/outgrowth and synapse stabilization during development, we now examined the contribution of A2AR to MF sprouting.A2AR blockade significantly attenuated status epilepticus(SE)-induced MF sprouting in Heart Puzzle Keychain a rat pilocarpine model.
This involves A2AR located in dentate granule cells since their knockdown selectively in dentate granule cells reduced MF sprouting, Exercise Equipment - Therapy Putty most likely through the ability of A2AR to induce the formation/outgrowth of abnormal secondary axons found in rat hippocampal neurons.These A2AR should be activated by extracellular ATP-derived adenosine since a similar prevention/attenuation of SE-induced hippocampal MF sprouting was observed in CD73 knockout mice.These findings demonstrate that A2AR contribute to epilepsy-related MF sprouting, most likely through the reactivation of the ability of A2AR to control axon formation/outgrowth observed during neurodevelopment.
These results frame the CD73-A2AR axis as a regulator of circuit remodeling in the mature brain.