Effects of Long-Term Caffeine Consumption on the Adenosine A1 Receptor in the Rat Brain: an In Vivo PET Study with [18F]CPFPX

Nabbi-Schroeter, D; Elmenhorst, David; Oskamp, Angela; Laskowski, S; Bauer, Andreas; Kroll, Tina

doi:10.1007/s11307-017-1116-4

Cited by 20 publications

(15 citation statements)

References 37 publications

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“…It has also been utilized to visualize and quantify the in vivo occupancy of the human cerebral adenosine A 1 receptor by caffeine [34], and demonstrated that its chronic use did not lead to persistent changes in functional availability of A 1 ARs [35].…”

Section: Radioligands and Radiotracersmentioning

confidence: 99%

Chemical Probes for the Adenosine Receptors

2019

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Research on the adenosine receptors has been supported by the continuous discovery of new chemical probes characterized by more and more affinity and selectivity for the single adenosine receptor subtypes (A1, A2A, A2B and A3 adenosine receptors). Furthermore, the development of new techniques for the detection of G protein-coupled receptors (GPCR) requires new specific probes. In fact, if in the past radioligands were the most important GPCR probes for detection, compound screening and diagnostic purposes, nowadays, increasing importance is given to fluorescent and covalent ligands. In fact, advances in techniques such as fluorescence resonance energy transfer (FRET) and fluorescent polarization, as well as new applications in flow cytometry and different fluorescence-based microscopic techniques, are at the origin of the extensive research of new fluorescent ligands for these receptors. The resurgence of covalent ligands is due in part to a change in the common thinking in the medicinal chemistry community that a covalent drug is necessarily more toxic than a reversible one, and in part to the useful application of covalent ligands in GPCR structural biology. In this review, an updated collection of available chemical probes targeting adenosine receptors is reported.

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Section: Radioligands and Radiotracersmentioning

confidence: 99%

Chemical Probes for the Adenosine Receptors

2019

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“…It is also impossible to ignore the different part of the investigated structures in the hypothalamic-pituitary-adrenocortical axis. Since caf-feine is a nonselective adenosine antagonist, it can modulate the metabolic pathways in this axis (Nabbi-Schroeter et al, 2018;Karaismailoglu et al, 2017;Xu et al, 2012), which will somehow affect the adaptive responses. First of all, it concerns adrenal glands that react sensitively to the formation and implementation of adaptive-compensatory reactions.…”

Section: Discussionmentioning

confidence: 99%

The features of summary background electric activity of the hypothalamus of rats under conditions of chronic caffeine alimentation

Turitskaya

LUKASHEV

Lyashenko

et al. 2018

Regul. Mech. Biosyst.

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One of the factors of the environment which essentially shifts homeostasis is diets which contain caffeine. The aim of the study was to find out the basic characteristics of background electrical activity of trophotrophic and ergotrophic zones of the hypothalamus in conditions of chronic caffeine alimentation. Experiments were carried out on non-linear white male rats. The first group consisted of control animals (n = 22). The second group (n = 24) was represented by the animals that were given pure caffeine in an amount of 150 mg/kg/day with their meal. The registration on a electrohypothalamogram was carried out in conditions of acute experiment, every 2 weeks for 12 weeks. The spectral (mkV2) and the normalized power (%) of electrohypothalamogram waves were analyzed within the common frequency band. The analysis of the results allowed us to establish a certain specificity of the reaction of the neuronal system of the trophotropic and ergotropic zones of the rat hypothalamus to the effect of chronic caffeine alimentation. The main difference in the reactive state of electrophysiological indices in the trophotrophic zone of rats is the lack of a typical desynchronization from the 4th to the 8th week of the study and the hypersynchronization after 12 weeks of the experiment. The most probable mechanism that explains the results obtained is the ultra-powerful GABA-ergic modulation of this zone, the main energy-accumulating center. Perhaps, this powerful inhibitory resource in this cerebral locus is the main stress-limiting factor that makes this zone of the central nervous system of rats less sensitive to caffeine exposure. Instead, under the influence of chronic caffeine load in the ergotropic zone of the hypothalamus, after 6 weeks of the experiment desynchronous high-frequency rhythms dominated. During the subsequent time of the experiment, we observed a decrease in both low-frequency and high-frequency components of the electrohypothalamogram of this zone. This gives reason to assume that the key component of the neurophysiological response of the posterior hypothalamus of rats to the caffeine ration is the powerful glutamatergic effects on the pre-synaptic and post-synaptic neurons under conditions of reactive exhaustion of local neurosynthetics. Caffeine depletion of the hypothalamic neurotransmission at the end of the experiment is replaced by an effective adaptive ergotropic restoration of neurosynthetic activity in this locus of the central nervous system of rats. Thus, caffeine has a powerful activating effect on the ergotropic function of the posterior hypothalamus of rats. Such a difference in the chronic effect of caffeine on the trophotropic and ergotropic zone of the rat hypothalamus is primarily due to the different mediator support of these zones underlying their physiological purpose. GABA is the main mediator of the trophotropic zone and the main neurotransmitter of its synchronous activity. At the same time, neurotransmitter support of the ergotropic zone is represented by glutamate, which, along with other agents, implements its desynchronous activity. Since caffeine stimulates excitation, activating the pathways traditionally associated with motivational and motor reactions in the brain, it can be assumed that this explains the fact of a more powerful influence of caffeine precisely on the ergotrophic zone of the hypothalamus.

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“…Pagnussat et al believe that A2ARs are necessary and sufficient for triggering memory impairment, and A1R may selectively participate in controlling memory impairment driven by cholinergic processes. Nabbi‐Schroeter et al suggested that caffeine, a nonselective antagonist of adenosine receptors, may protect against neuronal degeneration and death caused by β‐amyloid by blocking A2AR and observed that the A2BR antagonist has a certain protective effect against AD. In addition, there is an association between isoflurane exposure and spatial memory impairment, and declines in NR2B levels and increases in Aβ and P‐tau levels may be achieved by activating A1AR .…”

Section: The Role Of Adenosine and Its Receptors In Central Nervous Smentioning

confidence: 99%

Research progress on adenosine in central nervous system diseases

et al. 2019

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As an endogenous neuroprotectant agent, adenosine is extensively distributed and is particularly abundant in the central nervous system (CNS). Under physiological conditions, the concentration of adenosine is low intra‐ and extracellularly, but increases significantly in response to stress. The majority of adenosine functions are receptor‐mediated, and primarily include the A1, A2A, A2B, and A3 receptors (A1R, A2AR, A2BR, and A3R). Adenosine is currently widely used in the treatment of diseases of the CNS and the cardiovascular systems, and the mechanisms are related to the disease types, disease locations, and the adenosine receptors distribution in the CNS. For example, the main infarction sites of cerebral ischemia are cortex and striatum, which have high levels of A1 and A2A receptors. Cerebral ischemia is manifested with A1R decrease and A2AR increase, as well as reduction in the A1R‐mediated inhibitory processes and enhancement of the A2AR‐mediated excitatory process. Adenosine receptor dysfunction is also involved in the pathology of Alzheimer's disease (AD), depression, and epilepsy. Thus, the adenosine receptor balance theory is important for brain disease treatment. The concentration of adenosine can be increased by endogenous or exogenous pathways due to its short half‐life and high inactivation properties. Therefore, we will discuss the function of adenosine and its receptors, adenosine formation, and metabolism, and its role for the treatment of CNS diseases (such as cerebral ischemia, AD, depression, Parkinson's disease, epilepsy, and sleep disorders). This article will provide a scientific basis for the development of novel adenosine derivatives through adenosine structure modification, which will lead to experimental applications.

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Effects of Long-Term Caffeine Consumption on the Adenosine A1 Receptor in the Rat Brain: an In Vivo PET Study with [18F]CPFPX

Cited by 20 publications

References 37 publications

Chemical Probes for the Adenosine Receptors

Chemical Probes for the Adenosine Receptors

The features of summary background electric activity of the hypothalamus of rats under conditions of chronic caffeine alimentation

Research progress on adenosine in central nervous system diseases

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