Topic: Adenosine

Adenosine, through the A1 receptor (A1R), is an endogenous anticonvulsant. Development of adenosine receptor agonists as antiseizure drugs has been hampered by cardiac effects. A moderately A1R-selective agonist, MRS5474, has been reported to suppress seizures without appreciable cardiac action (Tosh et al., 2012, J Med Chem, 55:8075). We aimed at understanding its mechanism of action. MRS5474 (50-500nM) was devoid of effect upon rodent excitatory synaptic signals in hippocampal slices, except when hyperexcitability was previously induced in vivo or ex vivo. This contrasted with the effect of

Molecular signals mediating systemic inflammation entering the brain parenchyma to induce sepsis-associated encephalopathy (SAE) remain elusive. In this study, we demonstrate that peripheral lipopolysaccharide (LPS)-induced systemic inflammation could rapidly increase the plasma adenosine concentration, peaking at 6 hours post LPS injection (hpi). Using in vivo 2P-LSM imaging of adenosine sensor GRABAdo, we observed elevated adenosine levels in the cortex of awake mice, also peaking at 6 hpi. These concomitant pathological events strongly suggest adenosine in the circulation can join forces to

ATP/Adenosine, a type of neurotransmitter, has recently attracted attention as damage-associated molecular patterns (DAMPs) and has been reported to play an important role in the induction of inflammation via inflammasome. On the other hand, there have been few reports on in vivo measurements of ATP and adenosine in the synaptic cleft and/or extracellular spaces.Generally, in vivo measurement of neurotransmitter content in the synaptic cleft and/or extracellular spaces has been performed mainly by invasive methods such as micro dialysis. However, recently, GPCR-activation-based (GRAB) sensor w

Ecto-5'-nucleotidase (CD73) is an ecto-enzyme that hydrolyzes adenosine monophosphate to adenosine, which acts through one of four subtypes of adenosine receptors. Increased CD73 activity and expression in chronic neurodegenerative diseases leads to a higher concentration of adenosine in the extracellular space. This results in excessive activation of adenosine A2AR, which triggers proinflammatory signaling pathways that further promote neurodegeneration. Therefore, dual CD73/A2AR inhibition is a potential pharmacologic target in chronic neurodegeneration. In the present study, we used a novel

Adenosine acts as a fine regulator of synaptic plasticity in the adult brain. We showed a key role for the adenosine A2A receptor (A2AR) in the stabilization of nascent active GABAergic synapses during brain development (Gomez-Castro et al., Science 374 2021). Our data indicate that this regulation extends to glutamatergic synapses and involve neuroglial interactions. The suppression of neuronal A2AR with a shRNA approach in mixed neuron-glia cultures led to the loss of ~30% of glutamatergic synapses. Puzzlingly, activating A2AR in these cultures with a selective agonist (CGS21680) also led to

Parkinson's disease (PD) is considered the second most common neurodegenerative disease in the world. Animal models based on exposure to Paraquat (Pq) or 6-hydroxydopamine (6-OHDA) have been used to better understand and find new therapies for PD. Purinergic signaling has emerged as a pivotal factor in the progression of PD. We assessed the influence of Pq or 6-OHDA on ATP metabolism as well as nucleotide and nucleoside-metabolizing enzyme activities and gene expression in adult zebrafish brain. Adult zebrafish were injected i.p. with saline (vehicle) or Pq (10 or 20 mg/kg) with two days of in

Progesterone (P4) has shown promising results in diminishing the effects of cerebral hypoperfusion (CH) in prefrontal cortex. Therefore, our goal was to further analyze the neuroprotective mechanism of P4 in adult Wistar rats following bilateral occlusion of common carotid arteries (2VO). We investigated its impact on neurological function and activity of striatal extracellular purine metabolizing enzymes, CD39 and CD73. Following either sham or 2VO operation, for 7 consecutive days, animals (n=12) received s.c. treatments of commercial flax oil (V, 1 mg/kg) (Sham+V and 2VO+V groups) or 1.7 mg

The medial prefrontal cortex (mPFC) is a cortical brain region characterized by complex cognitive functions, such as working memory and decision making. These complex functions are based on a finely tuned interaction between excitatory pyramidal neurons, inhibitory GABAergic interneurons and astrocytes. Astrocytes as well as neurons express a variety of neurotransmitter receptors, the activation of which leads to an increase in intracellular calcium (Ca2+). The aim of this study was to characterize the purinergic Ca2+ signaling and to identify the involved receptors in astrocytes of the mPFC.C

Striatal dopamine (DA) is critical to the regulation of action selection and motivation. DA neurons have extensively branched axons which afford axonal regulation of DA release by diverse striatal neuromodulators including acetylcholine (ACh), GABA and adenosine, which regulate the amplitude and activity-sensitivity of DA release. Adrenoceptors are expressed throughout the striatum but their role, and that of norepinephrine (NE) as a potential striatal neuromodulator, is poorly understood. Given only a sparse norepinephrinergic input of the striatum but the dense innervation by DA, the endogen