Deletion of CD73 increases exercise power in mice

Aguiar, Aderbal S.; Speck, Ana Elisa; Canas, Paula M.; Cunha, Rodrigo A.

doi:10.1007/s11302-021-09797-4

Cited by 7 publications

(16 citation statements)

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“…Our results strengthen the hypothesis about the ergogenic mechanism of caffeine through adenosinergic antagonism in the central nervous system [7][8][9]16]. Mice treated with caffeine and SCH 58261 demonstrated increased running performance, while caffeine-treated forebrain A 2A R knockouts did not demonstrate this effect [16].…”

Section: Discussionsupporting

confidence: 86%

“…Davis first demonstrated that adenosine agonist 5′-N-ethylcarboxamide adenosine (NECA) injected into the rat ventricles increases running performance [7]. We then demonstrate the role of extracellular adenosine in the development of fatigue in mice [8] and the pivotal role of neuronal A 2A R in the mouse forebrain for the ergogenic effects of caffeine [1, 9]. On the other hand, the increase in A 2A R [10, 11] is a hypothetical mechanism for the fatigue symptom in neurological diseases [12].…”

Section: Introductionmentioning

confidence: 99%

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The striatum drives the ergogenic effects of caffeine

Alves

Speck

Farias

et al. 2022

Preprint

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Caffeine is one of the main ergogenic resources used in exercise and sports. Previously, we presented the ergogenic mechanism of caffeine through neuronal A2AR antagonism in the central nervous system [1]. We demonstrate here that the striatum rules the ergogenic effects of caffeine through neuroplasticity changes. Thirty-four Swiss (8-10 weeks, 47 ± 1.5 g) and twenty-four C57BL6 (8-10 weeks, 23.9 ± 0.4 g) adult male mice were challenged in behavior and electrophysiology experiments using caffeine and SH-SY5Y cells for energetic metabolism. Systemic (15 mg/kg, i.p.) or striatal (bilateral, 15 μg) caffeine was psychostimulant in the open field (p < 0.05) and increased gripping muscle power (p < 0.05). Caffeine also induced long-term potentiation (LTP) in striatal slices (p < 0.05) and increased mitochondrial mass (p < 0.05) and membrane potential p < 0.05) in SH-SY5Y dopaminergic cells. In summary, our results demonstrate that caffeine stimulation in the striatum produces ergogenic effects accompanied by an LTP, possibly associated with acute increased mitochondrial metabolism observed in dopaminergic cell lines.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

The striatum drives the ergogenic effects of caffeine

Alves

Speck

Farias

et al. 2022

Preprint

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“…We previously described that mice injected with AOPCP display a similar pattern of spontaneous locomotion in the open field compared to control mice [ 24 ] as well as a similar physical performance at low to moderate intensities [ 33 ] and a similar spatial reference memory performance [ 25 ]. The impact of AOPCP, applied intracerebroventricularly, was now tested in fear conditioning memory ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine A2A Receptor-Mediated Control of Fear Memory and Amygdala Plasticity

Simões

Gonçalves²,

Rial³

et al. 2022

IJMS

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Adenosine A2A receptors (A2AR) control fear memory and the underlying processes of synaptic plasticity in the amygdala. In other brain regions, A2AR activation is ensured by ATP-derived extracellular adenosine formed by ecto-5′-nucleotidase or CD73. We now tested whether CD73 is also responsible to provide for the activation of A2AR in controlling fear memory and amygdala long-term potentiation (LTP). The bilateral intracerebroventricular injection of the CD73 inhibitor αβ-methylene ADP (AOPCP, 1 nmol/ventricle/day) phenocopied the effect of the A2AR blockade by decreasing the expression of fear memory, an effect disappearing in CD73-knockout (KO) mice and in forebrain neuronal A2AR-KO mice. In the presence of PPADS (20 μM) to eliminate any modification of ATP/ADP-mediated P2 receptor effects, both AOPCP (100 μM) and the A2AR antagonist, SCH58261 (50 nM), decreased LTP magnitude in synapses of projection from the external capsula into the lateral amygdala, an effect eliminated in slices from both forebrain neuronal A2AR-KO mice and CD73-KO mice. These data indicate a key role of CD73 in the process of A2AR-mediated control of fear memory and underlying synaptic plasticity processes in the amygdala, paving the way to envisage CD73 as a new therapeutic target to interfere with abnormal fear-like emotional processing.

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“…Furthermore, the increased calcium concentrations in the muscle cytoplasm, increases calcium binding opportunities for troponin to expose myosin binding sites and thus enhance skeletal muscle contraction force (Smith, 2003;Hogervorst et al, 2008;Connell et al, 2016;Pires et al, 2018;Saville et al, 2018;Shabir et al, 2018;Franco-Alvarenga et al, 2019;Huertas et al, 2019;Aguiar et al, 2020;Cipollone et al, 2020;Machado et al, 2020;Sanchis et al, 2020;Wang et al, 2020;Lorenzo Calvo et al, 2021;Vázquez et al, 2022;Ágoston et al, 2022). Centrally, the most accepted mechanism of how CAF exerts its effect on cognition is its influence on the central neuronal adenosine receptors, specifically the A 1 and A 2A adenosine receptors (Fredholm et al, 1999;Dunwiddie and Masino, 2001;Smith, 2003;Borycz et al, 2007;Hogervorst et al, 2008;Pandolfo et al, 2013;Connell et al, 2016;Cunha, 2016;Leffa et al, 2018Leffa et al, , 2019Pires et al, 2018;Saville et al, 2018;Shabir et al, 2018;Franco-Alvarenga et al, 2019;Huertas et al, 2019;Lopes et al, 2019;Aguiar et al, 2020Aguiar et al, , 2021Cipollone et al, 2020;Machado et al, 2020;Sanchis et al, 2020;…”

Section: Neurobehavioral Cognitive and Neurophysiological Effects Of ...mentioning

confidence: 99%

“…Centrally, the most accepted mechanism of how CAF exerts its effect on cognition is its influence on the central neuronal adenosine receptors, specifically the A 1 and A 2A adenosine receptors (Fredholm et al, 1999;Dunwiddie and Masino, 2001;Smith, 2003;Borycz et al, 2007;Hogervorst et al, 2008;Pandolfo et al, 2013;Connell et al, 2016;Cunha, 2016;Leffa et al, 2018Leffa et al, , 2019Pires et al, 2018;Saville et al, 2018;Shabir et al, 2018;Franco-Alvarenga et al, 2019;Huertas et al, 2019;Lopes et al, 2019;Aguiar et al, 2020Aguiar et al, , 2021Cipollone et al, 2020;Machado et al, 2020;Sanchis et al, 2020;Wang et al, 2020;Lorenzo Calvo et al, 2021;Vázquez et al, 2022;Ágoston et al, 2022). Extracellular adenosine in the brain is formed by AMP-selective enzymes, such as CD73, and is dependent on the rate of synthesis and breakdown of ATP (Aguiar et al, 2021). CAF is an adenosine antagonist whereby it blocks adenosine binding to A 1 and A 2A receptors by reducing adenosine's ability to inhibit DA activity.…”

Section: Neurobehavioral Cognitive and Neurophysiological Effects Of ...mentioning

confidence: 99%

The therapeutic potential of exercise and caffeine on attention-deficit/hyperactivity disorder in athletes

Sogard

Mickleborough

2022

Front. Neurosci.

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Attention-deficit/hyperactivity disorder (ADHD) is characterized by evident and persistent inattention, hyperactivity, impulsivity, and social difficulties and is the most common childhood neuropsychiatric disorder, and which may persist into adulthood. Seventy to 80% of children and adults with ADHD are treated with stimulant medication, with positive response rates occurring for both populations. Medicated ADHD individuals generally show sustained and improved attention, inhibition control, cognitive flexibility, on-task behavior, and cognitive performance. The ethics of ADHD medication use in athletics has been a debated topic in sport performance for a long time. Stimulants are banned from competition in accordance with World Anti-Doping Association and National Collegiate Athletic Association regulations, due to their ability to not only enhance cognitive performance but also exercise performance. Limited research has been conducted looking at the differences in exercise performance variables in unmedicated ADHD verses medicated ADHD. Not all ADHD athletes choose stimulant medication in their treatment plan due to personal, financial, or other reasons. Non-stimulant treatment options include non-stimulant medication and behavioral therapy. However, the use of caffeinated compounds and exercise has both independently been shown to be effective in the management of ADHD symptoms in human studies and animal models. This mini review will discuss the effect of exercise and caffeine on neurobehavioral, cognitive, and neurophysiological factors, and exercise performance in ADHD athletes, and whether exercise and caffeine should be considered in the treatment plan for an individual with ADHD.

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Deletion of CD73 increases exercise power in mice

Cited by 7 publications

References 30 publications

The striatum drives the ergogenic effects of caffeine

The striatum drives the ergogenic effects of caffeine

CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine A2A Receptor-Mediated Control of Fear Memory and Amygdala Plasticity

The therapeutic potential of exercise and caffeine on attention-deficit/hyperactivity disorder in athletes

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