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Neuroprotective Interactions Between Delta-Opioid Receptors and Glutamatergic Signaling Mediate Hypoxia-Tolerance in Brain

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Neural Functions of the Delta-Opioid Receptor

Abstract

Delta-opioid receptors are a class of membrane proteins found throughout the nervous system. They have traditionally been associated with the transmission of sensations related to pain via neuromodulation of excitatory glutamatergic synaptic signaling. Research examining these interactions in nocireception and related anesthesia applications has demonstrated that delta-opioid receptors are capable of mediating glutamatergic signaling via both pre-synaptic and post-synaptic mechanisms. In addition to normal neurotransmission functions, derangements in glutamatergic signaling are also associated with pathological brain damage due to low oxygen stresses, such as hypoxia or ischemic stroke; delta-opioid receptors are capable of mediating neuroprotective responses to such stresses via the inhibition of deleterious excitatory glutamatergic signaling. Specifically, studies of the mechanisms of hypoxic or ischemic preconditioning have demonstrated that delta-opioid receptors are central triggers that mediate inducible neuroprotective mechanisms against acute hypoxic, ischemic, and glutamatergic stresses in mammalian brain, and recent evidence points to the modulation of glutamate receptors as a critical component of this neuroprotective mechanism. In addition, a recent study has demonstrated that endogenous activation of similar mechanisms contributes to the innate anoxia-tolerance of the brain of one of the most hypoxia-tolerant vertebrates identified—the Western Painted turtle, and that the mechanism of neuroprotection in this organism involves the direct inhibition of neuronal glutamatergic signaling at the post-synapse. This chapter will focus on the putative neuroprotective effects of delta-opioid receptor signaling in models of hypoxic preconditioning in mammal brain and also in glutamatergic channel arrest in turtle brain. Similarities between the underlying neuroprotective mechanisms against hypoxia and the mechanistic interactions in nocireception and analgesia will also be discussed.

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Correspondence to Matthew E. Pamenter Ph.D. .

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Pamenter, M.E. (2015). Neuroprotective Interactions Between Delta-Opioid Receptors and Glutamatergic Signaling Mediate Hypoxia-Tolerance in Brain. In: Xia, Y. (eds) Neural Functions of the Delta-Opioid Receptor. Springer, Cham. https://doi.org/10.1007/978-3-319-25495-1_8

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