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Oxygen Sensors of the Peripheral and Central Nervous Systems

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

Neural systems exposed to diminished oxygen availability have a compromised metabolism that leads to pathophysiological changes or neuronal death, depending on the severity and duration of oxygen deprivation. A distributed network of oxygen sensors responds to protect cells by slowing or ameliorating pathophysiological changes and forestalling neuronal death via short-term or long-term changes involving gene expression and the modification of sensors and effectors. In mammalian systems such protective changes are not sufficient to prevent damage under extreme conditions, unlike some hypoxia- and anoxia-tolerant vertebrates which demonstrate oxygen-dependent, reversible reprogramming to protect vital organs such as the brain and heart.

This chapter examines (1) the nature of the signal for oxygen sensors; (2) the molecules used to sense oxygen; (3) how the primary signal is generated, converted, and used in an oxygen-dependent manner; (4) how effector systems function in different cell types; and (5) how oxygen-sensing pathways are interconnected to more general protective stress responses which confer cross-protection for a number of physiological stressors.

While future therapies may focus on the activation of hypoxia-inducible factor (HIF) and its downstream gene products, selected gene products could be administered to reduce neuronal loss and improve recovery after acute insults due to ischemic events and degenerative diseases of the brain and retina. Activation of neuroprotective pathways by oxygen sensors and other physiological stressors could be used as pretreatment to minimize neurotrauma associated with neurosurgical procedures and as an ancillary treatment during early stages of rehabilitation.

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Abbreviations

HIF:

hypoxia-inducible factor

HREs:

hypoxia response elements

Hsps:

heat-shock proteins

iNOS:

inducible nitric oxide synthase

NE:

noradrenaline

ODG:

oxygen-dependent genes

ROS:

reactive oxygen species

TH:

tyrosine hydroxylase

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Authors
  1. G. M. C. Renshaw
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  2. M. Nikinmaa
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, New York, 10962, Orangeburg, USA

    Abel Lajtha (Director) (Director)

  2. University of Tennessee Health Science Center, 62 South Dunlap, 38163, Memphis, Tennessee, USA

    Dianna A. Johnson (Hiatt Professor of Ophthalmology Associate Vice Chancellor for Academic, Faculty and Student Affairs) (Hiatt Professor of Ophthalmology Associate Vice Chancellor for Academic, Faculty and Student Affairs)

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Renshaw, G.M.C., Nikinmaa, M. (2007). Oxygen Sensors of the Peripheral and Central Nervous Systems. In: Lajtha, A., Johnson, D.A. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30374-1_11

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