scholarly journals Striatal adenosine A2A receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Xiang-Shan Yuan ◽  
Lu Wang ◽  
Hui Dong ◽  
Wei-Min Qu ◽  
Su-Rong Yang ◽  
...  
Keyword(s):  
Globus Pallidus ◽  
Sleep Disturbances ◽  
Nrem Sleep ◽  
Inhibitory Synapses ◽  
Active Period ◽  
Promoting Effect ◽  
A2a Receptors ◽  
A2a Receptor ◽  
Receptor Neurons ◽  
Adenosine A2a

Dysfunction of the striatum is frequently associated with sleep disturbances. However, its role in sleep-wake regulation has been paid little attention even though the striatum densely expresses adenosine A2A receptors (A2ARs), which are essential for adenosine-induced sleep. Here we showed that chemogenetic activation of A2AR neurons in specific subregions of the striatum induced a remarkable increase in non-rapid eye movement (NREM) sleep. Anatomical mapping and immunoelectron microscopy revealed that striatal A2AR neurons innervated the external globus pallidus (GPe) in a topographically organized manner and preferentially formed inhibitory synapses with GPe parvalbumin (PV) neurons. Moreover, lesions of GPe PV neurons abolished the sleep-promoting effect of striatal A2AR neurons. In addition, chemogenetic inhibition of striatal A2AR neurons led to a significant decrease of NREM sleep at active period, but not inactive period of mice. These findings reveal a prominent contribution of striatal A2AR neuron/GPe PV neuron circuit in sleep control.

scholarly journals Die adenosien A1- en A2A-reseptoraffiniteit van ’n reeks 3,4-dihidropirimidoon-analoë

2017 ◽  
Vol 36 (1) ◽  
Author(s):  
Runako M. Katsidzira ◽  
Mietha M. Van der Walt ◽  
Jacobus J. Bergh ◽  
Gisella Terre’Blanche
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adenosine A2a Receptor ◽  
Adenosine A1 Receptor ◽  
Receptor Affinity ◽  
A2a Receptors ◽  
A2a Receptor ◽  
Adenosine A1 ◽  
A1 Receptor ◽  
Adenosine A2a

Parkinson’s disease is a complex neurodegenerative condition with current treatment only focussed on symptomatic therapy that does not slow or stop the progression of the disease. Since the discovery that adenosine A1 and A2A receptors are potential drug targets for the therapy of Parkinson’s disease, various research groups have attempted to identify adenosine antagonists. So the possibility exists that the administration of an adenosine A2A receptor antagonist may prevent further neurodegeneration. Furthermore, the antagonism of adenosine A1 receptors has the potential of treating Parkinson’s disease-associated cognitive deficits. Therefore, dual antagonism of adenosine A1 and A2A receptors would be of great benefit since this would potentially treat both the motor as well as the cognitive impairment associated with Parkinson’s disease. Based on the observation that a series of 1,4-dihydropyridine derivatives possess adenosine A1 and A2A receptor affinity, the current study investigated the potential of the structurally related 3,4-dihydropyrimidone analogues as adenosine A1 and A2A receptor antagonists. Overall, the 3,4-dihyropyrimidone analogues were found to possess weak affinity for the adenosine A2A receptor, but more promising adenosine A1 receptor affinity was found, ranging in the low micromolar range. Among the investigated compounds, the p-bromophenyl substituted dihydropyrimidone (6b) possesses the best adenosine A1 receptor affinity with a Ki value of 7.39 µM. In conclusion, this 3,4-dihydropyrimidone derivative can be used as a lead for the design of novel adenosine A1 receptor antagonists, although further structural modifications are required to enhance the adenosine A2A receptor affinity before a clinically viable candidate will be available as potential treatment of Parkinson’s disease.

scholarly journals Sake yeast induces the sleep-promoting effects under the stress-induced acute insomnia in mice

2021 ◽  
Author(s):  
Shohei Nishimon ◽  
Noriaki Sakai ◽  
Seiji Nishino
Keyword(s):  
Oral Administration ◽  
Core Body Temperature ◽  
Nrem Sleep ◽  
Stressful Environment ◽  
A2a Receptor ◽  
And Performance ◽  
Adenosine A2a ◽  
Core Body ◽  
Dose Dependent ◽  
A2ar Agonist

Abstract Sleep deprivation induces adverse effects on the health, productivity, and performance. The individuals who could not get enough sleep temporarily experience the symptoms of an induced acute insomnia. This study investigated the efficacy of sake yeast in treatment of acute insomnia in mice. The results of this study showed that sake yeast induced a significant dose-dependent wake reduction, a rapid eye movement (REM) and a non-REM (NREM) sleep enhancement during the first 6 h after the oral administration of sake yeast with locomotor activity and core body temperature decreases under the stressful environment in a new cage. In fact, the wake amounts at 3 h and 6 h were significantly reduced after the oral administration of sake yeast compared with the vehicle. The NREM sleep amounts at 3 h and 6 h significantly increased after the administration of sake yeast compared with the vehicle. The REM amount at 6 h significantly increased after the administration of sake yeast compared with the vehicle, but not at 3 h. The previous study suggested that the sleep-promoting effects of sake yeast could be referred from the activating effect of adenosine A2A receptor (A2AR). In conclusion, the sake yeast is a potential therapeutic agent for acute insomnia, being a A2AR agonist with stress-reducing and anti-anxiety properties, constituting a promising adjuvant treatment strategy for acute insomnia to traditional pharmacotherapy.

scholarly journals Adenosine A2A Receptor Antagonists Affects NMDA Glutamate Receptor Function. Potential to Address Neurodegeneration in Alzheimer’s Disease

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1075 ◽  
Author(s):  
Rafael Franco ◽  
Rafael Rivas-Santisteban ◽  
Mireia Casanovas ◽  
Alejandro Lillo ◽  
Carlos A. Saura ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glutamate Receptor ◽  
Expression System ◽  
Primary Cultures ◽  
Adenosine A2a Receptor ◽  
A2a Receptors ◽  
Adenosine A2a Receptor Antagonists ◽  
A2a Receptor ◽  
Adenosine A2a

(1) Background. N-methyl d-aspartate (NMDA) ionotropic glutamate receptor (NMDAR), which is one of the main targets to combat Alzheimer’s disease (AD), is expressed in both neurons and glial cells. The aim of this paper was to assess whether the adenosine A2A receptor (A2AR), which is a target in neurodegeneration, may affect NMDAR functionality. (2) Methods. Immuno-histo/cytochemical, biophysical, biochemical and signaling assays were performed in a heterologous cell expression system and in primary cultures of neurons and microglia (resting and activated) from control and the APPSw,Ind transgenic mice. (3) Results. On the one hand, NMDA and A2A receptors were able to physically interact forming complexes, mainly in microglia. Furthermore, the amount of complexes was markedly enhanced in activated microglia. On the other hand, the interaction resulted in a novel functional entity that displayed a cross-antagonism, that could be useful to prevent the exacerbation of NMDAR function by using A2AR antagonists. Interestingly, the amount of complexes was markedly higher in the hippocampal cells from the APPSw,Ind than from the control mice. In neurons, the number of complexes was lesser, probably due to NMDAR not interacting with the A2AR. However, the activation of the A2AR receptors resulted in higher NMDAR functionality in neurons, probably by indirect mechanisms. (4) Conclusions. A2AR antagonists such as istradefylline, which is already approved for Parkinson’s disease (Nouriast® in Japan and Nourianz® in the US), have potential to afford neuroprotection in AD in a synergistic-like fashion. i.e., via both neurons and microglia.

Adenosine A2A receptor stimulation decreases GAT-1-mediated GABA uptake in the globus pallidus of the rat

2006 ◽  
Vol 51 (1) ◽  
pp. 154-159 ◽  
Author(s):  
Brenda Gonzalez ◽  
Francisco Paz ◽  
Leonor Florán ◽  
Jorge Aceves ◽  
David Erlij ◽  
...  
Keyword(s):  
Globus Pallidus ◽  
Adenosine A2a Receptor ◽  
Gaba Uptake ◽  
Receptor Stimulation ◽  
A2a Receptor ◽  
Adenosine A2a

Striatal adenosine A2A receptor neurons regulate sleep behavior

2017 ◽  
Vol 40 ◽  
pp. e359
Author(s):  
X.-S. Yuan ◽  
L. Wang ◽  
H. Dong ◽  
R.-L. Li ◽  
W.-M. Qu ◽  
...  
Keyword(s):  
Adenosine A2a Receptor ◽  
Sleep Behavior ◽  
A2a Receptor ◽  
Receptor Neurons ◽  
Adenosine A2a

scholarly journals Exacerbation of C1q dysregulation, synaptic loss and memory deficits in tau pathology linked to neuronal adenosine A2A receptor

Brain ◽  
2019 ◽  
Vol 142 (11) ◽  
pp. 3636-3654 ◽  
Author(s):  
Kevin Carvalho ◽  
Emilie Faivre ◽  
Marie J Pietrowski ◽  
Xavier Marques ◽  
Victoria Gomez-Murcia ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Memory Deficits ◽  
Immune Dysregulation ◽  
Tau Pathology ◽  
Glutamatergic Synapses ◽  
Adenosine A2a Receptors ◽  
Synaptic Loss ◽  
A2a Receptors ◽  
A2a Receptor ◽  
Adenosine A2a

See Cunha (doi:10.1093/brain/awz335) for a scientific commentary on this article. Carvalho et al. provide clues to the onset of immune dysregulation underlying early synaptic loss in Alzheimer’s disease and tauopathies, by linking overactivation of adenosine A2A receptors in tau pathology to a particular microglial signature (upregulation of C1q and TREM2) allied to the loss of glutamatergic synapses and cognitive deficits.

Sign in / Sign up

Export Citation Format

Share Document