Ageing‐related decline in adenosine A1 receptor binding in the rat brain: An autoradiographic study

Meerlo, Peter; Román, Viktor; Farkas, Eszter; Keijser, Johannes; Nyakas, Csaba; Luiten, P.G.M.

doi:10.1002/jnr.20314

Cited by 35 publications

(14 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An imbalance in adenosine receptors has been observed in multiple conditions, 21 particularly with progressive aging, 18,19 which has consequences to their modulatory effects. 19,41 In the aged rat brain, adenosine A 1 receptor density is decreased, 47 particularly in hippocampus and cortex. 18 However, A 2A receptor levels are differently affected: they decrease in striatum, but in contrast there is an increase in their expression in cortical and hippocampal areas.…”

Section: Discussionmentioning

confidence: 99%

Adenosine A2A receptor blockade reverts hippocampal stress-induced deficits and restores corticosterone circadian oscillation

et al. 2012

View full text Add to dashboard Cite

Maternal separation (MS) is an early life stress model that induces permanent changes in the central nervous system, impairing hippocampal long-term potentiation (LTP) and spatial working memory. There are compelling evidences for a role of hippocampal adenosine A(2A) receptors in stress-induced modifications related to cognition, thus opening a potential window for therapeutic intervention. Here, we submitted rats to MS and evaluated the long-lasting molecular, electrophysiological and behavioral impairments in adulthood. We then assessed the therapeutic potential of KW6002, a blocker of A(2A) receptors, in stress-impaired animals. We report that the blockade of A(2A) receptors was efficient in reverting the behavior, electrophysiological and morphological impairments induced by MS. In addition, this effect is associated with restoration of the hypothalamic-pituitary-adrenal axis (HPA-axis) activity, as both the plasma corticosterone levels and hippocampal glucocorticoid receptor expression pattern returned to physiological-like status after the treatment. These results reveal the involvement of A(2A) receptors in the stress-associated impairments and directly in the stress response system by showing that the dysfunction of the HPA-axis as well as the long-lasting synaptic and behavioral effects of MS can be reverted by targeting adenosine A(2A) receptors. These findings provide a novel evidence for the use of adenosine A(2A) receptor antagonists as potential therapy against psychopathologies.

show abstract

Section: Discussionmentioning

confidence: 99%

Adenosine A2A receptor blockade reverts hippocampal stress-induced deficits and restores corticosterone circadian oscillation

et al. 2012

View full text Add to dashboard Cite

show abstract

“…The fact that the old rats failed to exhibit those changes associated with homeostatic rebound from sleep loss (increased delta, increased NR and increased sleep consolidation) may simply be because the sleep loss incurred by ICV Hcrt-1 in old rats was of insufficient magnitude to induce a homeostatic response. Nonetheless, previous studies have demonstrated that other known neurobiological mediators of homeostatic sleep regulation, including adenosine [Meerlo, et al, 2004; Murillo-Rodriguez, et al, 2004], are disrupted with age in Wistar rats.…”

Section: Discussionmentioning

confidence: 99%

The wake-promoting effects of hypocretin-1 are attenuated in old rats

Morairty

Wisor

Silveira

et al. 2011

Neurobiology of Aging

View full text Add to dashboard Cite

Disruption of sleep is a frequent complaint among elderly humans and is also evident in aged laboratory rodents. The neurobiological bases of age-related sleep/wake disruption are unknown. Given the critical role of the hypocretins in sleep/wake regulation, we sought to determine whether the wake-promoting effect of hypocretin changes with age in Wistar rats, a strain in which age-related changes in both sleep and hypocretin signaling have been reported. Intracerebroventricular infusions of hypocretin-1 (10 and 30 μg) significantly increased wake time relative to vehicle in both young (3 mos) and old (25 mos) Wistar rats. However, the magnitude and duration of the wake-promoting effect were attenuated with age. An increase of parameters associated with homeostatic sleep recovery after sleep deprivation, including non-rapid eye movement (NR) sleep time, NR delta power, the ratio of NR to rapid eye movement (REM) sleep, and NR consolidation, occurred subsequent to Hcrt-induced waking in young but not old rats. ICV infusions of hypocretin-2 (10 and 30 μg) produced fewer effects in both young and old rats. These data demonstrate that activation of a major sleep/wake regulatory pathway is attenuated in old rats.

show abstract

“…Given the more superficial sleep in old rats and the suggested role for adenosine in promoting SWS/SWA, these data indicated that the sensitivity of adenosine receptors declines with increasing age. In support of this hypothesis, autoradiography in rat brain slices and PET with 18 F-CPFPX in humans showed that adenosine A 1 receptor binding was significantly reduced with age in many cortical and subcortical brain regions (Meerlo et al, 2004; Meyer et al, 2007). No such studies were performed to date to investigate age-related changes in functional aspects of A 2A receptors in the brain.…”

Section: Advanced Age Alters Functional Aspects Of the Adenosinergic mentioning

confidence: 91%

Reduced Neurobehavioral Impairment from Sleep Deprivation in Older Adults: Contribution of Adenosinergic Mechanisms

Landolt¹,

Rétey²,

Adam³

2012

Front. Neur.

View full text Add to dashboard Cite

A night without sleep is followed by enhanced sleepiness, increased low-frequency activity in the waking EEG, and reduced vigilant attention. The magnitude of these changes is highly variable among healthy individuals. Findings in young men of low and high subjective caffeine sensitivity suggest that adenosinergic mechanisms contribute to inter-individual differences in sleep deprivation-induced changes in EEG theta activity, as well as optimal performance on the psychomotor vigilance task (PVT). In comparison to young subjects, healthy adults of older age typically feel less sleepy after sleep deprivation, and show fewer response lapses, and faster reaction times on the PVT, especially in the morning after the night without sleep. We hypothesized that age-related changes in adenosine signal transmission underlie reduced vulnerability to sleep deprivation in older individuals. To test this hypothesis, the combined effects of prolonged wakefulness and the adenosine receptor antagonist, caffeine, on an antero-posterior power gradient in EEG theta activity and PVT performance were analyzed in healthy older and caffeine-insensitive and -sensitive young men. The results show that age-related differences in sleep loss-induced changes in brain rhythmic activity and neurobehavioral functions are mirrored in young individuals of low and high sensitivity to the stimulant effects of caffeine. Moreover, the effects of sleep deprivation and caffeine on regional theta power and vigilant attention are inversely correlated across older and young age groups. Genetic variants of the adenosine A2A receptor gene contribute to individual differences in neurobehavioral performance in rested and sleep deprived state, and modulate the actions of caffeine in wakefulness and sleep. Based upon this evidence, we propose that age-related differences in A2A receptor-mediated signal transduction could be involved in age-related changes in the vulnerability to acute sleep deprivation.

show abstract

Ageing‐related decline in adenosine A1 receptor binding in the rat brain: An autoradiographic study

Cited by 35 publications

References 44 publications

Adenosine A2A receptor blockade reverts hippocampal stress-induced deficits and restores corticosterone circadian oscillation

Adenosine A2A receptor blockade reverts hippocampal stress-induced deficits and restores corticosterone circadian oscillation

The wake-promoting effects of hypocretin-1 are attenuated in old rats

Reduced Neurobehavioral Impairment from Sleep Deprivation in Older Adults: Contribution of Adenosinergic Mechanisms

Contact Info

Product

Resources

About