Overexpression of adenosine A2A receptors in rats: effects on depression, locomotion, and anxiety

Adenosine A2A receptors (A2AR) are a sub-type of receptors enriched in basal ganglia, activated by the neuromodulator adenosine, which interact with dopamine D2 receptors. Although this reciprocal antagonistic interaction is well-established in motor function, the outcome in dopamine-related behaviors remains uncertain, in particular in depression and anxiety. We have demonstrated an upsurge of A2AR associated to aging and chronic stress. Furthermore, Alzheimer's disease patients present A2AR accumulation in cortical areas together with depressive signs. We now tested the impact of overexpressing A2AR in forebrain neurons on dopamine-related behavior, namely depression. Adult male rats overexpressing human A2AR under the control of CaMKII promoter [Tg(CaMKII-hA2AR)] and aged-matched wild-types (WT) of the same strain (Sprague-Dawley) were studied. The forced swimming test (FST), sucrose preference test (SPT), and the open-field test (OFT) were performed to evaluate behavioral despair, anhedonia, locomotion, and anxiety. Tg(CaMKII-hA2AR) animals spent more time floating and less time swimming in the FST and presented a decreased sucrose preference at 48 h in the SPT. They also covered higher distances in the OFT and spent more time in the central zone than the WT. The results indicate that Tg(CaMKII-hA2AR) rats exhibit depressive-like behavior, hyperlocomotion, and altered exploratory behavior. This A2AR overexpression may explain the depressive signs found in aging, chronic stress, and Alzheimer's disease

Age-related shift in LTD is dependent on neuronal adenosine A(2A) receptors interplay with mGluR5 and NMDA receptors

Synaptic dysfunction plays a central role in Alzheimer's disease (AD), since it drives the cognitive decline. An association between a polymorphism of the adenosine A2A receptor (A2AR) encoding gene-ADORA2A, and hippocampal volume in AD patients was recently described. In this study, we explore the synaptic function of A2AR in age-related conditions. We report, for the first time, a significant overexpression of A2AR in hippocampal neurons of aged humans, which is aggravated in AD patients. A similar profile of A2AR overexpression in rats was sufficient to drive age-like memory impairments in young animals and to uncover a hippocampal LTD-to-LTP shift. This was accompanied by increased NMDA receptor gating, dependent on mGluR5 and linked to enhanced Ca(2+) influx. We confirmed the same plasticity shift in memory-impaired aged rats and APP/PS1 mice modeling AD, which was rescued upon A2AR blockade. This A2AR/mGluR5/NMDAR interaction might prove a suitable alternative for regulating aberrant mGluR5/NMDAR signaling in AD without disrupting their constitutive activity

Flora e aspectos auto-ecológicos de um encrave de cerrado na chapada do Araripe, Nordeste do Brasil Flora and autecology's aspects of a disjunction cerrado at Araripe plateau, Northeastern Brazil

Este trabalho visa conhecer a composição e riqueza florística, os padrões fenológicos reprodutivos, as síndromes de dispersão e as formas de vida das espécies de uma disjunção de cerrado em clima semi-árido, na chapada do Araripe, Estado do Ceará. Foram encontradas 107 espécies e 41 famílias. Fabaceae, Myrtaceae, Poaceae, Apocynaceae, Euphorbiaceae e Malpighiaceae foram as mais ricas em espécies. Foi feita a distribuição geográfica de 47 espécies arbustivas e arbóreas em 27 listagens de cerrados brasileiros. Doze espécies apresentaram ampla distribuição geográfica e 13 foram registradas apenas neste trabalho. Cerca de 76% das espécies floresceram e frutificaram no período chuvoso. As síndromes de dispersão predominantes foram: zoocoria, autocoria e anemocoria. O espectro biológico foi predominantemente constituído por fanerófitos (50,7%), hemicriptófitos (14,9%) e caméfitos (13,1%). O cerrado estudado apresentou menor riqueza taxonômica que os cerrados contínuos e comportamento das fenofases reprodutivas, percentagem de síndromes de dispersão e formas de vida similares.<br>This study subject to investigate the floristic composition and richness, the reproductive phenological patterns, the dispersal syndromes and life forms of species of a disjunt cerrado in semiarid climate at Araripe plateau during a one year period. We found 107 species and 41 families. Fabaceae, Myrtaceae, Poaceae, Apocynaceae, Euphorbiaceae and Malpighiaceae showed the largest number of species. For 47 of the woody species found, we studied the geographical distribution based on 27 papers of the Brazilian cerrados. Twelve species are of widespread occurence in the cerrado, and 13 are restricted to the Araripe plateau. Zoocory, autocory, and anemocory are the predominant syndromes of dispersal. The predominant life forms were phanerophytes (50.7%), hemicriptophytes (14.9%) and camephytes (13.1%). The cerrado of Araripe have lower species richness than continous cerrados, but a similar pattern of reproductive phenology, dispersal syndromes and life forms in more humid zones