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Cytochrome Oxidase in Neuronal Metabolism and Alzheimer’s Disease pp 233–261Cite as

Cytochrome Oxidase

A Predictive Marker of Neurodegeneration

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Abstract

Cytochrome oxidase has been used in the past as a marker of neuronal activity. We propose that cytochrome oxidase may also serve as a useful marker for predicting potential neurodegeneration, particularly following chronic brain hypoperfusion. This proposal is based on a series of experiments in rats subjected to mild chronic brain hypoperfusion and tested at determined time points for regional cytochrome oxidase activity, visuo-spatial memory, reactive astrocytosis, neurodegenerative changes and microtubule associated protein 2 (MAP-2). The results of these experiments suggest the following scenario: four weeks following chronic brain hypoperfusion, regional cytochrome oxidase activity is reduced in parallel with spatial memory function although no neurodegenerative changes are seen anywhere in the brain, despite an increased density of astrocytes in the hippocampus. After 8 weeks of ischemia, neurodegenerative changes are still absent but spatial memory remains depressed while the postsynaptic dendritic marker MAP-2 shows loss of immunostaining in the apical dendrites of CA1 neurons (suggesting continued metabolic dysfunction of these neurons). Twelve weeks after brain hypoperfusion, some neurodegenerative signs begin to be seen in CA1 neurons with continued MAP-2 reduction and reactive gliosis. If rats with chronic brain hypoperfusion are kept for 25 weeks, neuronal loss and extended hippocampal neurodegeneration with cortical atrophy can be seen. Neuronal loss and extension of neurodegeneration 25 weeks after chronic brain hypoperfusion are dependent on factors: age of animal, severity of the chronic ischemic insult and of ischemia. We suggest that the chronologic progression of memory dysfunction, gliosis and MAP-2 loss following mild but chronic brain hypoperfusion are due to lowered mitochondrial oxidative phosphorylation and reduced energy metabolism, initially in ischemic-sensitive neurons, such as in CA1. This energy metabolic down-regulation which is reflected by depressed cytochrome oxidase activity in the CA1 region, appears to precede neurodegenerative changes of CA1 neurons by many weeks. Cytochrome oxidase may be an important pathogenetic precursor of neurodegenerative pathology, particularly Alzheimer’s disease which shares many of the anatomic and cognitive deficits seen in the rat model.

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Authors and Affiliations

  1. Division of Neurosurgery and Department of Neuroscience, University of New Mexico, Albuquerque, New Mexico, 87106, USA

    N. P. Abdollahian & J. C. de la Torre

  2. Institute for Neuroscience, University of Texas, Austin, Austin, Texas, 78712, USA

    A. Cada & F. Gonzalez-Lima

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  1. N. P. Abdollahian
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  1. Institute for Neuroscience and Department of Psychology, The University of Texas at Austin, Mezes 330, 78712, Austin, Texas, USA

    F. Gonzalez-Lima

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Abdollahian, N.P., Cada, A., Gonzalez-Lima, F., de la Torre, J.C. (1998). Cytochrome Oxidase. In: Gonzalez-Lima, F. (eds) Cytochrome Oxidase in Neuronal Metabolism and Alzheimer’s Disease. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9936-1_9

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