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Increased Synaptic ATP Release and CD73-Mediated Formation of Extracellular Ade...

Dias, Liliana; Pochmann, Daniela; Lemos, Cristina; Silva, Henrique B.; Real, Joana I.; Gonçalves, Francisco Q.; Rial, Daniel; Gonçalves, Nélio

Increased ATP release and its extracellular catabolism through CD73 (ecto-5'-nucleotidase) lead to the overactivation of adenosine A2A receptors (A2AR), which occurs in different brain disorders. A2AR blockade blunts mood and memory dysfunction caused by repeated stress, but it is unknown if increased ATP release coupled to CD73-mediated formation of extracellular adenosine is responsible for A2AR overactivatio...


Editorial: 90th anniversary of the 1932 Sherrington and Adrian Nobel prize: mol...

Kessi, Miriam; Peng, Jing; He, Fang; Yin, Fei; Ferreira, Samira G.; Wei, Xiaofei


Downregulation of Sirtuin 1 Does Not Account for the Impaired Long-Term Potenti...

Lopes, Cátia R.; Silva, Joana S; Santos, Joana; Rodrigues, Matilde S.; Madeira, Daniela; Oliveira, Andreia; Moreira-de-Sá, Ana; Lourenço, Vanessa S.

Alzheimer's disease (AD), which predominantly affects women, involves at its onset a metabolic deregulation associated with a synaptic failure. Here, we performed a behavioral, neurophysiological and neurochemical characterization of 9-month-old female APPswe/PS1dE9 (APP/PS1) mice as a model of early AD. These animals showed learning and memory deficits in the Morris water maze, increased thigmotaxis and anxiet...


Effects of Chronic Caffeine Consumption on Synaptic Function, Metabolism and Ad...

Lopes, Cátia R.; Oliveira, Andreia; Gaspar, Ingride L.; Rodrigues, Matilde S.; Santos, Joana; Szabó, Eszter; Silva, Henrique B.; Tomé, Ângelo R.

Adenosine receptors mainly control synaptic function, and excessive activation of adenosine receptors may worsen the onset of many neurological disorders. Accordingly, the regular intake of moderate doses of caffeine antagonizes adenosine receptors and affords robust neuroprotection. Although caffeine intake alters brain functional connectivity and multi-omics analyses indicate that caffeine intake modifies syn...


Brain Iron Deficiency Changes the Stoichiometry of Adenosine Receptor Subtypes ...

Rodrigues, Matilde S.; Ferreira, Samira G.; Quiroz, César; Earley, Christopher J; García-Borreguero, Diego; Cunha, Rodrigo A.; Ciruela, Francisco

Brain iron deficiency (BID) constitutes a primary pathophysiological mechanism in restless legs syndrome (RLS). BID in rodents has been widely used as an animal model of RLS, since it recapitulates key neurochemical changes reported in RLS patients and shows an RLS-like behavioral phenotype. Previous studies with the BID-rodent model of RLS demonstrated increased sensitivity of cortical pyramidal cells to relea...


Control of glutamate release by complexes of adenosine and cannabinoid receptors

Köfalvi, Attila; Moreno, Estefanía; Cordomí, Arnau; Cai, Ning-Sheng; Fernández-Dueñas, Victor; Ferreira, Samira G.; Guixà-González, Ramón

It has been hypothesized that heteromers of adenosine A2A receptors (A2AR) and cannabinoid CB1 receptors (CB1R) localized in glutamatergic nerve terminals mediate the integration of adenosine and endocannabinoid signaling involved in the modulation of striatal excitatory neurotransmission. Previous studies have demonstrated the existence of A2AR-CB1R heteromers in artificial cell systems. A dependence of A2AR s...


Control of glutamate release by complexes of adenosine and cannabinoid receptors

Köfalvi, Attila; Moreno, Estefanía; Cordomí, Arnau; Cai, Ning-Sheng; Fernández-Dueñas, Victor; Ferreira, Samira G.; Guixà-González, Ramón

Background: It has been hypothesized that heteromers of adenosine A2A receptors (A2AR) and cannabinoid CB1 receptors (CB1R) localized in glutamatergic nerve terminals mediate the integration of adenosine and endocannabinoid signaling involved in the modulation of striatal excitatory neurotransmission. Previous studies have demonstrated the existence of A2AR-CB1R heteromers in artificial cell systems. A dependen...


Region-specific control of microglia by adenosine A2A receptors: uncoupling anx...

Duarte, Joana Mendes; Gaspar, Rita; Caetano, Liliana; Patrício, Patrícia; Cunha, Carina Isabel Soares; Pinheiro, António Maria Restolho Mateus

Epidemiologic studies have provided compelling evidence that prenatal stress, through excessive maternal glucocorticoids exposure, is associated with psychiatric disorders later in life. We have recently reported that anxiety associated with prenatal exposure to dexamethasone (DEX, a synthetic glucocorticoid) correlates with a gender-specific remodeling of microglia in the medial prefrontal cortex (mPFC), a cor...


Adenosine A2A Receptors in the Rat Prelimbic Medial Prefrontal Cortex Control D...

Leffa, Douglas T; Pandolfo, Pablo; Gonçalves, Nélio; Machado, Nuno J.; de Souza, Carolina M; Real, Joana I.; Silva, Antonio C.; Silva, Henrique B.

Adenosine A2A receptors (A2ARs) were recently described to control synaptic plasticity and network activity in the prefrontal cortex (PFC). We now probed the role of these PFC A2AR by evaluating the behavioral performance (locomotor activity, anxiety-related behavior, cost-benefit decision making and working memory) of rats upon downregulation of A2AR selectively in the prelimbic medial PFC (PLmPFC) via viral s...


Adenosine A2A Receptors Control Glutamatergic Synaptic Plasticity in Fast Spiki...

Kerkhofs, Amber; Canas, Paula M.; Timmerman, A. J.; Heistek, Tim S.; Real, Joana I.; Xavier, Carolina; Cunha, Rodrigo A.; Mansvelder, Huibert D.

Adenosine A2A receptors (A2AR) are activated upon increased synaptic activity to assist in the implementation of long-term plastic changes at synapses. While it is reported that A2AR are involved in the control of prefrontal cortex (PFC)-dependent behavior such as working memory, reversal learning and effort-based decision making, it is not known whether A2AR control glutamatergic synapse plasticity within the ...


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