Thebromine Targets Adenosine Receptors to Control Hippocampal Neuronal Function and Damage

被引:4
作者
Valada, Pedro [1 ]
Alcada-Morais, Sofia [1 ]
Cunha, Rodrigo A. [1 ,2 ]
Lopes, Joao Pedro [1 ]
机构
[1] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, P-3004504 Coimbra, Portugal
[2] Univ Coimbra, Fac Med, P-3004504 Coimbra, Portugal
关键词
theobromine; caffeine; adenosine receptors; synaptic transmission; synaptic plasticity; Alzheimer's disease; LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; XANTHINE DERIVATIVES; MEMORY IMPAIRMENT; A(2A) RECEPTORS; AMYLOID-BETA; CAFFEINE; THEOBROMINE; METHYLXANTHINES; CONSUMPTION;
D O I
10.3390/ijms231810510
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu M) 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 A(1)R with DPCPX (100 nM) eliminated the theobromine-dependent facilitation of synaptic transmission, whereas the A(2A)R antagonist SCH58261 (50 nM), as well as the genetic deletion of A(2A)R, 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 A beta(1-42) 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.
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页数:16
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