Biology subjects

Aguiar, A. S.

Publications and source records attributed to Aguiar, A. S..

5 recordsLinked to original sources

bioRxiv2023

The Striatal Heterodimers A2AR-D2Rs Are Linked To Ergogenic Effects Of Caffeine

Adenosine 2A receptors (A2ARs) are abundant in the striatum, and they are found co-localized with dopamine D2 receptors (D2R) and in the heterodimer form A2AR-D2R. Previous we demonstrated that caffeine delays central fatigue through adenosine 2A receptors (A2ARs) antagonism, striatal neuroplasticity and mitochondrial metabolism enhancement. In this study we demonstrate the participation of striatal A2AR-D2R in the ergogenic outcomes. Two-hundred swiss adult mice were treated systemically (i.p.) and centrally (striatum-st.) with caffeine, SCH58261 (A2AR antagonist), DPCPX (A1R antagonist) and haloperidol (D2R antagonist), and performed the open field test, treadmill incremental exercise and grip strength meter test We observed that A2AR-D2R antagonic effects are linked to motor control (p < 0.05) and enhancement of power (p < 0.05). However, the role of A2AR-D2R in the mechanism of strength generation seems to differ from motor control.

neuroscience↗

bioRxiv2022

The striatum drives the ergogenic effects of caffeine

Caffeine is one of the main ergogenic resources used in exercise and sports. Previously, we reported the ergogenic mechanism of caffeine through neuronal A2AR antagonism in the central nervous system [1]. We now demonstrate 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 C57BL/6J (8-10 weeks, 23.9 {+/-} 0.4 g) adult male mice were studied behaviorly and electrophysiologically using caffeine and energy metabolism was studied in SH-SY5Y cells. Systemic (15 mg/kg, i.p.) or striatal (bilateral, 15 g) caffeine was psychostimulant in the open field (p < 0.05) and increased grip efficiency (p < 0.05). Caffeine also shifted long-term depression (LTD) to potentiation (LTP) in striatal slices and increased the mitochondrial mass (p < 0.05) and membrane potential (p < 0.05) in SH-SY5Y dopaminergic cells. Our results demonstrate the role of the striatum in the ergogenic effects of caffeine, with changes in neuroplasticity and mitochondrial metabolism.

neuroscience↗

bioRxiv2021

Improved exercise anaerobic power and less central fatigue in CD73 knockout mice

Ecto-5-nucleotidase or CD73 is the main source of extracellular adenosine involved in the activation of adenosine A2A receptors, responsible for the ergogenic effects of caffeine. We now investigated the role of CD73 in exercise by comparing female wild-type (WT) and CD73 knockout (KO) mice in a treadmill graded test to evaluate running power, oxygen uptake [Formula], and respiratory exchange ratio (RER) - the gold standards characterizing physical performance. Spontaneous locomotion in the open field and submaximal running power and [Formula] in the treadmill were similar between CD73-KO and WT mice; [Formula] also demonstrated equivalent aerobic power, but CD73-KO mice displayed a 43.7{+/-}4.2% larger critical power (large effect size, P<0.05) and 3.8{+/-}0.4% increase of maximum RER (small effect size, P<0.05). Thus, KO of CD73 was ergogenic, i.e., it increased physical performance.

neuroscience↗

bioRxiv2021

Exercise Attenuates Sickness Behavior And Protects Against Dopaminergic Impairment Induced By Neuroinflammation

Neuroinflammation affects dopamine metabolism and produces a set of symptoms known as sickness behavior, including fever, anhedonia, anorexia, weight loss, decreased sociability and mobility, and cognitive impairment. Motor and cognitive impairments related to sickness behavior are associated with dopamine (DA) metabolism imbalance in the prefrontal cortex. Lipopolysaccharide (LPS) administration induces neuroinflammation and causes sickness behavior in mice, while physical exercise has anti-inflammatory properties and may attenuate sickness behavior and DA impairment. We investigated the effect of exercise on DA levels and sickness behavior induced by LPS in mice. Adult Swiss male mice (8-10 weeks, 47.1 {+/-} 0.7 g, n=495) performed six weeks of voluntary exercise in free-running wheels (RW group) or had the blocked wheel in their cages (sedentary, SED group). After six weeks of exercise, both groups received an intraperitoneal injection (i.p.) of either saline (SAL) or LPS (0.33 mg/kg, i.p.). All animals were submitted to behavioral tests for sickness behavior assessment (fatigue, locomotion, anhedonia, and social interaction). Neuroinflammation markers and DA metabolism were assessed in the prefrontal cortex. LPS administration provoked anorexia, body weight loss, impaired motor function, social withdrawal, and anhedonia. This sickness behavior was accompanied by reduced cortical DA metabolism and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC). Neuroinflammation was confirmed through increased levels of the proinflammatory cytokines IL-1{beta} and IL-6. Inflammation was also confirmed in the blood by an increased content of IL-1{beta}. Physical exercise intervention prevented animals from neurochemical, biochemical, and behavioral alterations. These findings provide new evidence of physical exercises potential as an environmental approach to treating neuroinflammatory conditions.

animal behavior and cognition↗

bioRxiv2020

Neuronal adenosine A2A receptors signal ergogenic effects of caffeine

Ergogenic aid is a substance or method used for enhancing exercise and sports performance. Caffeine is the most used ergogenic aid for athletes, but the mechanisms are still unknown. Forty-two adult female (19{+/-}0.6 g) and 40 male mice (24{+/-}0.4 g) from a global and forebrain A2AR knockout and colony (FMUC, University of Coimbra) underwent an open field and ergospirometry exercise test. Caffeine (15 mg/kg, i.p.) and SCH 58261 (1 mg/kg, i.p.) were administered 15 minutes before the animals ran to exhaustion. We also evaluate the estrous cycle and infrared temperature (rest and recovery). Caffeine was psychostimulant in wild type females and males, but we observed this expected effect of SCH-58261 only in males. Caffeine and SCH-58261 were also ergogenic for wild type animals, that is, they increased running power and maximal O2 consumption ([Formula]O2max). The psychostimulant and ergogenic effects of caffeine and SCH-58261 disappeared in A2AR knockout females (global) and males (forebrain). The estrous cycle did not influence any evaluated parameters, as well as exercise-induced hyperthermia was similar between savages and knockouts. Our results suggest that the neuronal A2AR receptors signal the ergogenic effects of caffeine in female and male mice.

physiology↗