STRESS EXACERBATES NEURON LOSS AND CYTOSKELETAL PATHOLOGY IN THE HIPPOCAMPUS

Glucocorticoids (GCs), the adrenal steroids secreted during stress, en danger the hippocampus, compromising its ability to survive neurologic al insults. GCs probably do so by disrupting energetics in the hippoca mpus, thus impairing its ability to contain damaging fluxes of excitat ory amino acids and calcium. Superficially, these observations suggest that stress itself should also exacerbate the toxicity of neurologica l insults. However, most studies have involved unphysiologic GC manipu lations, limiting speculations about the endangering effects of stress . In this study, rats were infused with the excitotoxin kainic acid (K A) after either having been adrenalectomized and replaced with a range of physiologic concentrations of GCs, or having been stressed intermi ttently. We observed that within the CA3 region, increasing CORT conce ntrations exacerbated the KA-induced neuron loss, the extent of tau im munoreactivity, and of spectrin proteolysis. The transitions from low to high basal GC concentrations and from high basal to stress GC value s were both associated with significant exacerbation of neuron loss an d tau immunoreactivity; the extent of spectrin proteolysis was less se nsitive to increments in GCs. As would be expected from these data, ex posure to intermittent stress prior to KA infusion also exacerbated ne uron loss, tau immunoreactivity, and spectrin proteolysis in CA3. Thus , physiological elevations of GCs, and stress itself, can exacerbate h ippocampal neuron loss and the attendant degenerative markers followin g an excitotoxic insult. Of significance, seizure and hypoxia-ischemia provoke considerable GC stress responses, which may thus worsen the r esultant damage. Furthermore, a number of neuropsychiatric disorders, as well as aging, are associated with elevated basal GC concentrations , which may endanger the hippocampus in the event of neurological insu lt.