Age-dependent and hypoxic/ischemic changes in akt/protein kinase B activation in rat hippocampus

Date

2003-12

Journal Title

Journal ISSN

Volume Title

Publisher

Texas Tech University

Abstract

Increased vulnerability to neuronal injury following ischemia in the aging brain has been well documented in humans as well as in rat models, especially within the hippocampus. An early response to hypoxia/ischemia is the transient and reversible depression of synaptic transmission, which is mediated by adenosine acting on neuronal adenosine Ai receptors. This depression of synaptic transmission is believed to be neuroprotective. Adenosine in turn activates the PI3K-Akt survival pathway, which is believed to exert neuroprotection from ischemic damage. Akt or Protein Kinase B is of particular interest as its activation may be a critical regulator of neuronal survival. Recent studies have suggested that this pathway is downregulated with aging in various non-neural tissues.

The response to cerebral ischemia or stroke is thought to exhibit an age-related impairment, with a disproportionate increase in morbidity with age. Stroke is the third largest killer after heart disease and cancer in the United States; almost 700,000 people are affected annually, most of them being elderly individuals. Though there is a strong connection between stroke-related morbidity and aging, the precise cause for this increased susceptibility is not known. It is imperative, now more than ever before, to investigate this problem, as the proportion of elderly in our population is ever increasing.

Our current knowledge seems to suggest that the extent of neuronal injury is dependent on the fine balance that exists between apoptotic and survival pathways. There is substantial evidence that the Akt-mediated survival pathway is suppressed with age, though this has never been shown in neuronal tissue.

This thesis explores our hypothesis that that the increased damage following cerebral hypoxia in the aged brain is due to an age-related impairment of the neuroprotective pathway mediated by adenosine and Akt.


TTUHSC -- Molecular Biophysics

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Unrestricted.

Keywords

Aging -- Research, Hippocampus (Brain) -- Research, Cardiovascular system, Rats -- Research, Neurons -- Drug effects, Cardiovascular system, Rats -- Research, Mammals, Ischemia

Citation