Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors

Cunha, Rodrigo A.

doi:10.1016/s0197-0186(00)00034-6

Cited by 560 publications

(472 citation statements)

References 219 publications

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“…A possible explanation for the significant interactions between age, caffeine and TOD in data set two may be due to alterations (specifically a decline), in adenosine receptor expression with increasing age (Cunha, 2001). This may result in changes in the degree of adenosine antagonism that caffeine can induce.…”

Section: Resultsmentioning

confidence: 98%

Time of day and caffeine influence some neuropsychological tests in the elderly.

Walters¹,

Lesk²

2015

Psychological Assessment

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We report that performance on neuropsychological tests used in the diagnosis of dementia can be influenced by external factors such as time of day (TOD) and caffeine. This study investigates TOD effects on cognitive performance in the elderly. The optimal TOD at which an individual is at their maximal arousal alters with age and in the elderly typically occurs in the morning. Neuropsychological test scores from healthy elderly participants were analysed to determine whether TOD affected performance. Interactions between caffeine and TOD were also investigated. Across two data sets that were analysed, significant TOD effects were noted for Pattern Comparison Speed (PCS), Letter Comparison Speed (LCS), Trail Making Test Part A, Mini Mental State Examination (MMSE) and the Graded NamingTest (GNT), revealing a decline in test scores as TOD increases. Significant interactions between TOD, age and the PCS, LCS and Trail Making part A were noted in data set one. In data set two, where caffeine intake had been controlled for, significant interactions between caffeine, TOD and scores on the MMSE and GNT were found. The TOD and caffeine effects highlight the need to control for these external factors when scoring the assessments. This conclusion has implications for the clinical procedure of diagnosis and treatment of dementia and Alzheimer's.

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Section: Resultsmentioning

confidence: 98%

Time of day and caffeine influence some neuropsychological tests in the elderly.

Walters¹,

Lesk²

2015

Psychological Assessment

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“…Thus, the role of adenosine in the brain is currently considered to be mediated by a balanced activation of A 1 and A 2A receptors, as shall be detailed in this review. It is hoped that greater experimental efforts as well as novel tools will allow a novel perspective on the eventual relevance of the less abundant A 2B Rs and A 3 Rs.…”

Section: Adenosine Receptorsmentioning

confidence: 99%

“…Its intra-cellular concentration in basal conditions is typically around 10Y50 nM in the cell types where it was so far quantified (reviewed in Cunha [1]). This intracellular concentration of adenosine is tightly linked to the energy charge of the cells, in the sense that small decreases in the energy charge (sometimes considered equivalent to the concentration of ATP) cause a disproportionate larger increase in the intracellular levels of adenosine (reviewed in Cunha [1]). The impact of changes in the intracellular levels of adenosine on the primary metabolism has not yet been explored.…”

Section: Introductionmentioning

confidence: 99%

“…In general, most mammalian cell types are equipped with adenosine A 1 receptors (A 1 Rs), whose activation causes a decrease in the rate of metabolism, allowing the cell to cope better with noxious stimuli. Thus, adenosine fulfils an homeostatic role in most cell types (see [2]), whereas a noxious stimuli reaching a particular cell causes a slight drop in energy charge that is converted into a large change in the intracellular levels of adenosine that diffuses out of the cell and signals to neighbouring cells via A 1 Rs the presence of a noxious stimuli, preparing neighbouring cells to handle better this noxious stimuli (by generally decreasing their rate of metabolism).…”

Section: Introductionmentioning

confidence: 99%

“…But adenosine fulfils other particular roles in the brain, apart from its general homeostatic role. In fact, the brain is the tissue by far with the greatest density of the most abundant adenosine A 1 Rs, which play key roles in controlling neuronal excitability and in particular neurotransmitter release, as will be discussed in the section BModulatory roles of adenosine.Â nd several lines of evidence (reviewed in Cunha [1]) indicate that this particular neuromodulatory role of adenosine is independent of changes in the energy charge of brain cells, i.e. the neuromodulatory role of adenosine is independent of the homeostatic role of adenosine.…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Cunha

2005

Purinergic Signalling

484

432

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Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A 1 receptors (A 1 Rs) and the less abundant, but widespread, facilitatory A 2A Rs. It is commonly assumed that A 1 Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A 1 R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A 1 Rs in chronic noxious situations. In contrast, A 2A Rs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A 2A R antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A 2A R antagonists as novel protective agents in neurodegenerative diseases such as Parkinson's and Alzheimer's disease, ischemic brain damage and epilepsy. The greater interest of A 2A R blockade compared to A 1 R activation does not mean that A 1 R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A 2A R antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A 1 Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different.Abbreviations: Ab -b-amyloid peptide; A 1 Rs -A 1 receptors; A 2A Rs -A 2A

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Adenosine A₁ Receptor mRNA Expression by Neurons and Glia in the Auditory Forebrain

Hackett

2018

The Anatomical Record

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In the brain, purines such as ATP and adenosine can function as neurotransmitters and co‐transmitters, or serve as signals in neuron–glial interactions. In thalamocortical (TC) projections to sensory cortex, adenosine functions as a negative regulator of glutamate release via activation of the presynaptic adenosine A1 receptor (A1R). In the auditory forebrain, restriction of A1R‐adenosine signaling in medial geniculate (MG) neurons is sufficient to extend LTP, LTD, and tonotopic map plasticity in adult mice for months beyond the critical period. Interfering with adenosine signaling in primary auditory cortex (A1) does not contribute to these forms of plasticity, suggesting regional differences in the roles of A1R‐mediated adenosine signaling in the forebrain. To advance understanding of the circuitry, in situ hybridization was used to localize neuronal and glial cell types in the auditory forebrain that express A1R transcripts (Adora1), based on co‐expression with cell‐specific markers for neuronal and glial subtypes. In A1, Adora1 transcripts were concentrated in L3/4 and L6 of glutamatergic neurons. Subpopulations of GABAergic neurons, astrocytes, oligodendrocytes, and microglia expressed lower levels of Adora1. In MG, Adora1 was expressed by glutamatergic neurons in all divisions, and subpopulations of all glial classes. The collective findings imply that A1R‐mediated signaling broadly extends to all subdivisions of auditory cortex and MG. Selective expression by neuronal and glial subpopulations suggests that experimental manipulations of A1R‐adenosine signaling could impact several cell types, depending on their location. Strategies to target Adora1 in specific cell types can be developed from the data generated here. Anat Rec, 301:1882–1905, 2018. © 2018 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

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Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors

Cited by 560 publications

References 219 publications

Time of day and caffeine influence some neuropsychological tests in the elderly.

Time of day and caffeine influence some neuropsychological tests in the elderly.

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Adenosine A₁ Receptor mRNA Expression by Neurons and Glia in the Auditory Forebrain

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Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors

Cited by 560 publications

References 219 publications

Time of day and caffeine influence some neuropsychological tests in the elderly.

Time of day and caffeine influence some neuropsychological tests in the elderly.

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Adenosine A1 Receptor mRNA Expression by Neurons and Glia in the Auditory Forebrain

Contact Info

Product

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Adenosine A₁ Receptor mRNA Expression by Neurons and Glia in the Auditory Forebrain