Thebromine Targets Adenosine Receptors to Control Hippocampal Neuronal Function and Damage.
Int J Mol Sci
; 23(18)2022 Sep 10.
Article
em En
| MEDLINE
| ID: mdl-36142422
ABSTRACT
Theobromine is a caffeine metabolite most abundant in dark chocolate, of which consumption is linked with a lower risk of cognitive decline. However, the mechanisms through which theobromine affects neuronal function remain ill-defined. Using electrophysiological recordings in mouse hippocampal synapses, we now characterized the impact of a realistic concentration of theobromine on synaptic transmission and plasticity. Theobromine (30 µM) facilitated synaptic transmission while decreasing the magnitude of long-term potentiation (LTP), with both effects being blunted by adenosine deaminase (2 U/mL). The pharmacological blockade of A1R with DPCPX (100 nM) eliminated the theobromine-dependent facilitation of synaptic transmission, whereas the A2AR antagonist SCH58261 (50 nM), as well as the genetic deletion of A2AR, abrogated the theobromine-induced impairment of LTP. Furthermore, theobromine prevented LTP deficits and neuronal loss, respectively, in mouse hippocampal slices and neuronal cultures exposed to Aß1-42 peptides, considered a culprit of Alzheimer's disease. Overall, these results indicate that theobromine affects information flow via the antagonism of adenosine receptors, normalizing synaptic plasticity and affording neuroprotection in dementia-related conditions in a manner similar to caffeine.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cafeína
/
Adenosina Desaminase
Limite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Portugal