INTRACEREBROVENTRICULAR INJECTION OF STREPTOZOTOCIN INDUCES DISCRETE LOCAL CHANGES IN CEREBRAL GLUCOSE-UTILIZATION IN RATS

The purpose of the present study was to investigate whether or not cer ebral glucose utilization is changed locally after damage of the neuro nal insulin receptor by means of intracerebroventricular (icv) strepto zotocin (STZ) administered in a subdiabetogenic dosage (1.5 mg/kg bw.) . STZ was administered at the start of the study, and 2 and 21 days la ter bilaterally into the cerebral ventricles in rats of a mean age of 18 months. The local distribution of cerebral glucose utilization was analyzed in conscious rats on the 42nd day after the first STZ injecti on using the quantitative (C-14)-2-deoxyglucose method. Of the 35 brai n structures investigated from autoradiograms of brain sections, 17 sh owed a reduction in glucose utilization. Decreases in glucose utilizat ion were observed in the frontal, parietal, sensory motor, auditory an d entorhinal cortex and in all hippocampal subfields. In contrast, glu cose utilization was increased in two white matter structures. The dec rease in cerebral glucose utilization observed in cortical and hippoca mpal areas in the present study may correspond to changes in morphobio logical parameters which have been found in patients with Alzheimer's disease. The present data are in accordance with the hypothesis that a n impairment in the control of neuronal glucose metabolism at the insu lin receptor site may exist in sporadic dementia of Alzheimer type (DA T), and can be studied by the icv STZ animal model.