The response of synaptosomes isolated from Wistar non-diabetic rats and Goto-Kakizaki (GK) diabetic rats to the beta-amyloid fragment Abeta25-35 was compared. The synaptosomal redox activity, evaluated by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, was shown to be decreased in GK rats (72.8 +/- 7.45% of MTT reduction). However, the reduction of MTT was decreased in synaptosomes of Wistar rats upon Abeta25-35 treatment (84.47 +/- 3.73%), while in GK rats it was not affected. Abeta25-35 induced lipid peroxidation in synaptosomes of Wistar rats, but not in that of GK rats, leading to an 1.5-fold increase in thiobarbituric acid reactive substances (TBARS) levels. In the absence of Abeta25-35, basal TBARS levels were 1.6-fold higher in GK rats. In the former preparations, the content in vitamin E was also higher (2-fold). A decrease in ATP levels, of about 2-fold, was observed in synaptosomes of Wistar rats treated with Abeta25-35, while no significant changes were observed in synaptosomes of GK rats. No significant differences between the two groups were detected in the basal ATP levels. The extrasynaptosomal accumulation of aspartate and glutamate increased upon Abeta25-35 treatment, only in synaptosomes of Wistar rats (aspartate and glutamate accumulation increased by 1.1-fold and 1.5-fold, respectively), while the accumulation of glycine increased in both Wistar (by 1.8-fold) and GK (by 2.2-fold) rats. No statistical differences in the basal accumulation of aminoacids were observed. These results show that synaptosomes of GK diabetic rats have a lower redox activity, but are less susceptible to the Abeta25-35-induced toxicity. Data also suggest that oxidative stress occurs in this hyperglycemia animal model and that an increase in the antioxidant defense systems may exert protection against toxic insults. This mechanism, occuring in the early phases of diabetes, may correspond to an adaptive response.
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