Mild hypothermia protects synaptic transmission from experimental ischemia through reduction in the function of nucleoside transporters in the mouse hippocampus. (February 2020)

• Record Type: Journal Article
• Authors: Oyama, Yu; Ono, Kouki; Kawamura, Masahito
• Is Part Of: Neuropharmacology. Volume 163(2020)
• Publication Date: 2020-02
• Subjects: Adenosine A1 receptors -- Therapeutic hypothermia -- Patch clamp -- Field recordings -- Acute hippocampal slices; A1R adenosine A1 receptor -- aCSF artificial cerebrospinal fluid -- OGD oxygen-glucose deprivation -- fEPSP field excitatory postsynaptic potentials -- IAMPA AMPA-evoked currents -- evoked PSC evoked postsynaptic currents -- Ade adenosine -- CPA N6-Cyclopentyladenosine -- DPCPX 8-cyclopentyl-1, 3-dipropylxanthine -- DIPY Dipyridamole -- NBTI S-(4-Nitrobenzyl)-6-thioinosine -- EHNA erythro-9-(2-Hydroxy-3-nonyl) adenine; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.107853
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Ischemia, a severe metabolic stress, increases adenosine levels and causes the suppression of synaptic transmission through adenosine A1 receptors. Although temperature also regulates extracellular adenosine levels, the effect of temperature on ischemia-induced activation of adenosine receptors is not yet fully understood. Here we examined the role of adenosine A1 receptors in mild hypothermia-mediated neuroprotection during the acute phase of ischemia. Severe ischemia-induced neurosynaptic impairment was reproduced by oxygen-glucose deprivation at normothermia (36 °C) and assessed with extracellular recordings or whole-cell patch clamp recordings in acute hippocampal slices in mice. Mild hypothermia (32 °C) induced the protection of synaptic transmission by activating adenosine A1 receptors. Stricter hypothermia (28 °C) caused additional neuroprotective effects by extending the onset time to anoxic depolarization; however, this effect was not associated with adenosine A1 receptors. The response of exogenous adenosine-induced inhibition of hippocampal synaptic transmission was increased by lowering the temperature to 32 °C or 28 °C. Hypothermia also reduced the function of dipryidamole-sensitive nucleoside transporters. These findings suggest that an increased response of adenosine A1 receptors, caused by a reduction in the function of nucleoside transporters, is one mechanism by which therapeutic hypothermia (usually used within the mild range) mediates neurosynaptic protection in the acute phase of stroke. Highlights: Mild hypothermia (32 °C) causes neurosynaptic protection during ischemia. Hypothermia-mediated neurosynaptic protection is caused by activation of A1 R. Stricter hypothermia (28 °C) offers additional protection in an A1 R-independent manner. Activation of A1 R by exogenous adenosine is increased during hypothermia. Lowering the temperature reduces the function of nucleoside transporter.