[Abstract Title]. - Society for Neuroscience

suggested that dominant and submissive characteristics might be differentially related to
pathological conditions. In this regard, however, some of these outcomes may be more evident in
dominant than in submissive mice.
Disclosures: M. Audet , None; B. Wann, None; J. Gibb, None; H. Anisman, None.
Poster
280. Stress and the Brain: Stress and Neuroimmunology I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 280.8/NN8
Topic: E.06.c. Stress and neuroimmunology
Support: NIH Grant AGO20633
Title: Chronic exposure to glucocorticoids worsens neuron death in a mouse model of
excitotoxicity
Authors: *S. F. SORRELLS, C. D. MUNHOZ, R. M. SAPOLSKY;
Dept Biolog Sci., Stanford Univ., Stanford, CA
Abstract: During neurological injury, long-term exposure to stress levels of glucocorticoids
(GCs) has a detrimental effect on neuron survival. An extensive literature now demonstrates that
exposure to stress levels of GCs, signaling through GR, can impair the ability of neurons in the
hippocampus, cortex, and striatum to survive a variety of necrotic neurological insults [1]. GCs
worsen neuron death in these situations in part because they inhibit glucose uptake, which
exacerbates declining ATP concentrations, mitochondrial potential, and reuptake of excitotoxic
glutamate from the synapse. GCs also compromise the ability of post-synaptic neurons to
sequester and/or extrude free cytosolic calcium, and to contain and quench oxygen radicals [3].
Most of this work has been done in rats; however there is also some evidence that GCs adversely
affect injured neurons in mice [4-7].
We sought to determine whether multiple GC injections exacerbate the neurotoxicity caused by
kainic acid (KA) in mice. We treated C57Bl/6 male mice with vehicle or 10mg/kg corticosterone
(the rodent GC) per day for three days prior to KA administration and measured the amount of
excitotoxic neuron death in the hippocampus. Alternatively, animals were given s.c. pellets of
varying corticosterone concentrations for the same duration. All treatments yielded circulating
blood corticosterone concentrations in the physiological mid- to high-stress range.
By 24 hours post-injury, there was a trend towards an increased number of fluorojade B positive
neurons in the GC treated animals. This indicated that GC treatments might be increasing
neurodegeneration. After 72 hours, GC treatment caused a measurable increase in lesions visible