Chapter

Selective Neuronal Vulnerability in the Hippocampus: Relationship to Neurological Diseases and Mechanisms for Differential Sensitivity of Neurons to Stress

Elias K. Michaelis

in The Clinical Neurobiology of the Hippocampus

Published in print July 2012 | ISBN: 9780199592388
Published online September 2012 | e-ISBN: 9780199949922 | DOI: http://dx.doi.org/10.1093/acprof:oso/9780199592388.003.0004
Selective Neuronal Vulnerability in the Hippocampus: Relationship to Neurological Diseases and Mechanisms for Differential Sensitivity of Neurons to Stress

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The phenomenon of selective neuronal vulnerability to neurological diseases or insults, such as ischemia-reperfusion, brain trauma, and ageing-associated neurodegeneration, was described in the hippocampus nearly a century ago. The hippocampus has been the focus for many of the studies designed to identify the stresses to which neurons respond differentially, as well as the molecular, cellular and physiological mechanisms that may be responsible for such differential response patterns. Although final conclusions have not yet been reached on the mechanisms for differential neuronal responses to stress and disease, genomic and proteomic analyses, in conjunction with biochemical and physiological measurements, are beginning to point to endogenous differences between vulnerable and resistant populations of neurons. Collectively, these studies have identified differential patterns of energy metabolism, generation of reactive oxygen species, handling of transient intracellular calcium elevations, and the activity of the neurotransmitter glutamate, as some of the key processes that lead to selective sensitivity to neurological stresses. The genomic and proteomic analyses have revealed that differences in gene expression related to inflammatory and immune responses and responses to oxidative stress represent endogenous processes differentially expressed in neurons selectively vulnerable to stresses. The same is true for genes involved in DNA, RNA, and protein repair. Cells that are more resistant to stresses and disease conditions express genes for energy generation, nervous system development, and synaptic transmission at higher levels than those found in vulnerable neurons. The molecular pathways identified above and described in this chapter may eventually determine the targets for future therapeutic interventions for neurodegenerative diseases.

Keywords: CA1/CA3 neurons, ischaemia/reperfusion; ageing; neurodegenerative diseases; energy metabolism; oxidative stress; calcium regulation; glutamate transmission; genomic analyses

Chapter.  18080 words.  Illustrated.

Subjects: Neuroscience

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