Adenosine A₁ receptor-mediated protection of mouse hippocampal synaptic transmission against oxygen and/or glucose deprivation: a comparative study

Abstract

Adenosine receptors are widely expressed in the brain, and adenosine is a key bioactive substance for neuroprotection. In this article, we clarify systematically the role of adenosine A1 receptors during a range of timescales and conditions when a significant amount of adenosine is released. Using acute hippocampal slices obtained from mice that were wild type or null mutant for the adenosine A1 receptor, we quantified and characterized the impact of varying durations of experimental ischemia, hypoxia, and hypoglycemia on synaptic transmission in the CA1 subregion. In normal tissue, these three stressors rapidly and markedly reduced synaptic transmission, and only treatment of sufficient duration led to incomplete recovery. In contrast, inactivation of adenosine A1 receptors delayed and/or lessened the reduction in synaptic transmission during all three stressors and reduced the magnitude of the recovery significantly. We reproduced the responses to hypoxia and hypoglycemia by applying an adenosine A1 receptor antagonist, validating the clear effects of genetic receptor inactivation on synaptic transmission. We found activation of adenosine A1 receptor inhibited hippocampal synaptic transmission during the acute phase of ischemia, hypoxia, or hypoglycemia and caused the recovery from synaptic impairment after these three stressors using genetic mutant. These studies quantify the neuroprotective role of the adenosine A1 receptor during a variety of metabolic stresses within the same recording system. NEW & NOTEWORTHY Deprivation of oxygen and/or glucose causes a rapid adenosine A1 receptor-mediated decrease in synaptic transmission in mouse hippocampus. We quantified adenosine A1 receptor-mediated inhibition during and synaptic recovery after ischemia, hypoxia, and hypoglycemia of varying durations using a genetic mutant and confirmed these findings using pharmacology. Overall, using the same recording conditions, we found the acute response and the neuroprotective ability of the adenosine A1 receptor depended on the type and duration of deprivation event.

Neuromodulation and neuroprotective effects of chlorogenic acids in excitatory synapses of mouse hippocampal slices

“…A particular ability of chlorogenic acids to control synaptic dysfunction in pathological-like conditions was further confirmed by the observation that chlorogenic acids were able to accelerate the recovery of synaptic transmission upon re-oxygenation after oxygen–glucose deprivation, an in vitro model of ischemia 45 , 46 . Although with a limited number of experiments, the overall qualitative analysis of the data indicates that the exposure to chlorogenic acids during reoxygenation bolsters the recovery of synaptic transmission and the subsequent ability to engage synaptic plasticity phenomena.…”

“…To test if chlorogenic acids could prevent the deterioration of synaptic function, we next resorted to an in vitro model of ischemia-induced depression of synaptic transmission. Ischemia was modelled by exposing hippocampal slices to oxygen and glucose deprivation (OGD 45 , 46 ). Chlorogenic acids were applied at the onset of the re-oxygenation period since our previous studies indicated an efficiency of polyphenolic compounds to prevent ischemia-induced brain damage when applied after the onset of ischemia 47 .…”

“…The in vitro ischemia model consisted of a brief oxygen/glucose deprivation (OGD) applied directly to the superfused hippocampal slices, as previously described 45 , 46 . The OGD challenge consisted of replacing the oxygenated ACSF with an ACSF with 7 mM sucrose/3 mM glucose instead of 10 mM glucose and saturated with 95% N 2 /5% CO 2 , for 7 min, and thereafter resuming superfusion with the 10 mM glucose, oxygenated ACSF (re-oxygenation period).…”

Adenosine and Ketogenic Treatments

“…Ischemic or hypoxic events can lead to seizures, and cause of a high percentage of neonatal seizures 55 and high levels of adenosine are released in such events. 56 Pretreatment with KD [57][58][59][60] or ketone bodies 61 in rodent models is neuroprotective. Yang et al addressed the possible involvement of adenosine in this phenomenon.…”

Perineuronal nets affect memory and learning after synapse withdrawal

“…Animal models of hibernation can address the mechanisms of re-wiring. One model of short-term hibernation-like state (HLS) involve administration of 5'-AMP combined with cooling to activate the hypothalamic nuclei for induction of torpor (Carlin et al, 2018;Carlin et al, 2017;Carlin et al, 2016;Kawamura et al, 2019). Induction of torpor/HLS?…”