The Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York 10021, USA
Previous studies from our laboratory demonstrated that chronic
stress produces molecular, morphological, and ultrastructural
changes in the rat hippocampus that are accompanied by cognitive
deficits. Glucocorticoid impairment of glucose utilization is
proposed as a causative factor involved in stress-induced changes.
Current studies have examined the neurological changes induced
by stress in rats with a preexisting strain upon their homeostatic
load-namely, in streptozotocin (stz)-diabetic rats. Administration
of stz (70 mg/kg, iv) produced diabetic symptoms such as weight
loss, polyuria, polydipsia, hyperglycemia, and neuroendocrine
dysfunction. Morphological analysis of hippocampal neurons revealed
that diabetes alone produced dendritic atrophy of CA3 pyramidal
neurons, an effect potentiated by 7 days of restraint stress.
Analysis of genes critical to neuronal homeostasis revealed
that glucose transporter 3 (GLUT3) mRNA and protein levels were
specifically increased in the hippocampus of diabetic rats,
while stress had no effect upon GLUT3 expression. Insulin-like
growth factor (IGF) receptor expression was also increased in
the hippocampus of diabetic rats subjected to stress. In spite
of the activation of these adaptive mechanisms, diabetic rats
subjected to stress also had signs of neuronal damage and oxidative
damage. Collectively, these results suggest that the hippocampus
of diabetic rats is extremely susceptible to additional stressful
events, which in turn can lead to irreversible hippocampal damage.
