Adenosine A2A receptors control synaptic remodeling in the adult brain.
Sci Rep
; 12(1): 14690, 2022 08 29.
Article
em En
| MEDLINE
| ID: mdl-36038626
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 a rat pilocarpine model. This involves A2AR located in dentate granule cells since their knockdown selectively in dentate granule cells reduced MF sprouting, 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adenosina
/
Receptor A2A de Adenosina
/
Epilepsia do Lobo Temporal
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Portugal