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Adenosine caffeine structure9/8/2023 ![]() ![]() In the recent years, multiple lines of evidence have suggested an association between adenosine modulation and stress response. Moreover, higher cortisol levels have been also associated with more rapid Alzheimer’s disease (AD) progression 5 and systemic administration of glucocorticoids or stress were shown to potentiate memory impairments, hippocampal damage, β-amyloid formation and Tau accumulation in transgenic AD mice 6, 7, 8. This is probably a consequence of dendritic retraction and hippocampal dysfunction that we have shown to occur upon chronic stress 1. Increased glucocorticoid activity has also been associated with greater hippocampal atrophy and memory impairment in the elderly 3. Accordingly, in a large study of elder humans aged 50–70 years, elevated salivary levels of cortisol were found to be correlated with poor cognitive function 4. The hippocampus plays a crucial role in regulating HPA axis 2 and excessive glucocorticoid production disrupts the regulatory circuit that connects the hippocampus and the hypothalamus.Īge-related disorders are associated with downregulation of glucocorticoid receptors (GR) in the hippocampus, and subsequent desensitization of the regulatory feedback to the hypothalamus 3. Release of cortisol from the adrenal cortex is under tight regulation of this hypothalamic–pituitary–adrenal (HPA) axis. This supports the idea that the procognitive effects of A 2AR antagonists, namely caffeine, on Alzheimer’s and age-related cognitive impairments may rely on its ability to modulate GR actions.Įxcessive glucocorticoid production associated with chronic or severe stress impairs hippocampal neuronal function and predisposes the organism to neurodegeneration 1. We provide the first demonstration that A 2AR is a major regulator of GR function and that this functional interconnection may be a trigger to age-related memory deficits. The synaptic plasticity and memory deficits triggered by GR in the hippocampus are amplified by A 2AR over-activation and were rescued by anti-A 2AR therapy finally, we demonstrate that A 2AR act on GR nuclear translocation and GR-dependent transcriptional regulation. We now show that inducing A 2AR 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. These observations suggest that A 2AR over-activation and glucocorticoid dysfunction are key events in age-related hippocampal deficits but their direct connection has never been explored. We have previously shown that an anti-A 2AR therapy reverts age-like memory deficits, by reestablishment of the hypothalamic-pituitary-adrenal (HPA) axis feedback and corticosterone circadian levels. If you’re a smoker, likely you can drink caffeine up to a later time and still be OK in terms of sleeping.Caffeine is associated with procognitive effects in humans by counteracting overactivation of the adenosine A 2A receptor (A 2AR), which is upregulated in the human forebrain of aged and Alzheimer’s disease (AD) patients. For example, people who smoke metabolize caffeine in the liver about twice as fast. Van Dam: Your lifestyle makes a difference. You may want to say, “Well, let’s try to cut down caffeine and not drink it after a certain time in the afternoon and see if that improves my sleeping habits.” So it’s really something every individual has to experiment with for themselves – how much caffeine they drink and when they drink it.ĬNN: What factors affect how we react to caffeine? Sign up for CNN’s SLEEP, BUT BETTER newsletter And similarly, it can interfere with a good night’s sleep. If you’re getting tremors, feeling suddenly nervous, or your heart rate is changing, it could well be that you’re drinking too much caffeine. And that’s because different people react very differently to caffeine. Rob van Dam: That sounds like a simple question, but unfortunately there’s not one answer to it. ![]() Spicy Homemade Buffalo Wings with Dip and Beer ShutterstockĨ eating habits that can interfere with sleepĬNN: How do we know when it’s time to stop drinking coffee during the day so we can still get a good night’s sleep? ![]()
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