Summary: A new study describes the mechanism by which caffeine can counteract cognitive deficits associated with aging in rats.
Source: INSERM
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| When the same animals were treated with a caffeine analogue, which blocks the action of adenosine A2A receptors, both memory and stress related deficits were normalized. NeuroscienceNews.com image is for illustrative purposes only.
A study published in the journal Scientific Reports from Nature publishing group, describes the mechanism by which caffeine counteracts age-related cognitive deficits in animals.
The study coordinated by Portuguese researchers from Instituto de Medicina Molecular (iMM Lisboa) and collaborators from Inserm in Lille, France, along with teams from Germany and United States, showed that the abnormalexpression of a particular receptor – the adenosine A2A, target for caffeine – in the brain of rats induces an aging-like profile namely memory impairments linked to the loss of stress controlling mechanisms.
“This is part of a larger study initiated 4 years ago in which we identified the role of this receptor in stress, but we did not know whether its activation would be sufficient to trigger all the changes. We now found that by altering the amount of this receptor alone in neurons from hippocampus and cortex – memory related areas – is sufficient to induce a profile that we designate as ‘early-aging’ combining the memory loss and an increase in stress hormones in plasma (cortisol)” – explains Luisa Lopes, Group Leader at iMM Lisboa and the coordinator of the study.
When the same animals were treated with a caffeine analogue, which blocks the action of adenosine A2A receptors, both memory and stress related deficits were normalized.
avid Blum, from Inserm research director, adds: “In elderly people, we know there is an increase of stress hormones that have an impact on memory. Our work supports the view that the procognitive effects of A2AR antagonists, namely caffeine, observed in Alzheimer’s and age-related cognitive impairments may rely on this ability to counteract the loss of stress controlling mechanisms that occurs upon aging”
This is important not only to understand the fundamental changes that occur upon aging, but it also identifies the dysfunctions of the adenosine A2A receptor as a key player in triggering these changes. And a very appealing therapeutic target” – concludes Luisa Lopes.
“Alzheimer & Tauopahies” laboratory at UMR-S 1172 Inserm/Université Lille 2/CHRU-Lille is a world class research laboratory interested in the molecular, cellular, and physiological aspects of Alzheimer’s Disease and dementia. The lab is part of the LabEx DISTALZ (national consortium on AD) and of the LICEND excellence centre for neurodegenerative diseases.
Source: Juliette Hardy – INSERM
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function” by
Vânia L. Batalha, Diana G. Ferreira, Joana E. Coelho, Jorge S. Valadas, Rui Gomes, Mariana Temido-Ferreira, Tatiana Shmidt, Younis Baqi, Luc Buée, Christa E. Müller, Malika Hamdane, Tiago F. Outeiro, Michael Bader, Sebastiaan H. Meijsing, Ghazaleh Sadri-Vakili, David Blum and Luísa V. Lopes in Scientific Reports. Published online August 11 2016 doi:10.1038/srep31493
Abstract
The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function
Caffeine is associated with procognitive effects in humans by counteracting overactivation of the adenosine A2A receptor (A2AR), which is upregulated in the human forebrain of aged and Alzheimer’s disease (AD) patients. We have previously shown that an anti-A2AR therapy reverts age-like memory deficits, by reestablishment of the hypothalamic-pituitary-adrenal (HPA) axis feedback and corticosterone circadian levels. These observations suggest that A2AR over-activation and glucocorticoid dysfunction are key events in age-related hippocampal deficits; but their direct connection has never been explored. We now show that inducing A2AR overexpression in an aging-like profile is sufficient to trigger HPA-axis dysfunction, namely loss of plasmatic corticosterone circadian oscillation, and promotes reduction of GR hippocampal levels. The synaptic plasticity and memory deficits triggered by GR in the hippocampus are amplified by A2AR over-activation and were rescued by anti-A2AR therapy; finally, we demonstrate that A2AR act on GR nuclear translocation and GR-dependent transcriptional regulation. We provide the first demonstration that A2AR is a major regulator of GR function and that this functional interconnection may be a trigger to age-related memory deficits. This supports the idea that the procognitive effects of A2AR antagonists, namely caffeine, on Alzheimer’s and age-related cognitive impairments may rely on its ability to modulate GR actions.
“The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function” by
Vânia L. Batalha, Diana G. Ferreira, Joana E. Coelho, Jorge S. Valadas, Rui Gomes, Mariana Temido-Ferreira, Tatiana Shmidt, Younis Baqi, Luc Buée, Christa E. Müller, Malika Hamdane, Tiago F. Outeiro, Michael Bader, Sebastiaan H. Meijsing, Ghazaleh Sadri-Vakili, David Blum and Luísa V. Lopes in Scientific Reports. Published online August 11 2016 doi:10.1038/srep31493
http://neurosciencenews.com/caffeine-aging-cognition-4937/
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