| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Porciúncula, Lisiane O. Canas, Paula M. Machado, Nuno J. Müller, Christa E. Ardais, Ana Paula Agostinho, Paula Cunha, Rodrigo A. Rodrigues, Ana Lúcia S. Santana, Magda Chen, Jiang Fan Tomé, Ângelo R. Kaster, Manuella P. Baqi, Younis Silva, Henrique B. Nunes, Ana |
| Description |
Author Affiliation: Kaster MP ( CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal); Machado NJ ( CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal); Silva HB ( CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal); Nunes A ( CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal); Ardais AP ( CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal); Santana M ( CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal); Baqi Y ( Pharmaceutical Institute, University of Bonn, D-53121 Bonn, Germany); Müller CE ( Pharmaceutical Institute, University of Bonn, D-53121 Bonn, Germany); Rodrigues AL ( Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil); Porciúncula LO ( Departament of Biochemistry, Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, Rio Grande do Sul, Brazil.); Chen JF ( Department of Neurology and Pharmacology, Boston University School of Medicine, Boston, MA 02118); Tomé ÂR ( CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal); Agostinho P ( CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal); Canas PM ( CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal); Cunha RA ( CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal); |
| Abstract |
The consumption of caffeine (an adenosine receptor antagonist) correlates inversely with depression and memory deterioration, and adenosine $A_{2A}$ receptor $(A_{2A}R)$ antagonists emerge as candidate therapeutic targets because they control aberrant synaptic plasticity and afford neuroprotection. Therefore we tested the ability of $A_{2A}R$ to control the behavioral, electrophysiological, and neurochemical modifications caused by chronic unpredictable stress (CUS), which alters hippocampal circuits, dampens mood and memory performance, and enhances susceptibility to depression. CUS for 3 wk in adult mice induced anxiogenic and helpless-like behavior and decreased memory performance. These behavioral changes were accompanied by synaptic alterations, typified by a decrease in synaptic plasticity and a reduced density of synaptic proteins (synaptosomal-associated protein 25, syntaxin, and vesicular glutamate transporter type 1), together with an increased density of $A_{2A}R$ in glutamatergic terminals in the hippocampus. Except for anxiety, for which results were mixed, CUS-induced behavioral and synaptic alterations were prevented by (i) caffeine (1 g/L in the drinking water, starting 3 wk before and continued throughout CUS); (ii) the selective $A_{2A}R$ antagonist KW6002 (3 mg/kg, p.o.); (iii) global $A_{2A}R$ deletion; and (iv) selective $A_{2A}R$ deletion in forebrain neurons. Notably, $A_{2A}R$ blockade was not only prophylactic but also therapeutically efficacious, because a 3-wk treatment with the $A_{2A}R$ antagonist {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304","term_text":"SCH58261"}}SCH58261 (0.1 mg/kg, i.p.) reversed the mood and synaptic dysfunction caused by CUS. These results herald a key role for synaptic $A_{2A}R$ in the control of chronic stress-induced modifications and suggest $A_{2A}R$ as candidate targets to alleviate the consequences of chronic stress on brain function. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
25 |
| Volume Number |
112 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2015-06-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Caffeine Pharmacology Memory Disorders Prevention & Control Mood Disorders Neurons Drug Effects Receptor, Adenosine A2A Stress, Psychological Complications Animals Etiology Mice Mice, Inbred C57BL Metabolism Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
