Melatonin reduces membrane rigidity and oxidative damage in the brain of SAMP8 mice

Abstract We evaluated the autophagy-lysosomal pathway and membrane fluidity in brain cells and mitochondrial membranes obtained from senescence-accelerated (SAMP8 ) and senescence-resistant (SAMR1 ) mice at 5 and 10 months of age. Moreover, we studied whether chronic treatment from age 1 to 10 months with melatonin stabilizes membrane fluidity. Fluidity was measured by polarization changes of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene- p -toluene sulfonate. Results showed that in untreated animals at 5 months of age, synaptosomal and mitochondrial fluidity was decreased in SAMP8 compared to SAMR1 , as was the cathepsin D/B ratio, indicating dysfunction of the autophagy-lysosomal pathway. Moreover, we detected synaptosomal rigidity and programmed cell death capability in both groups at 10 months of age. Mitochondrial fluidity, however, did not show a significant age-dependent change but was lower in SAMP8 than in SAMR1 at the 5- and 10-month time points. Melatonin administration prevented rigidity in the mitochondrial membrane and seemed to decrease age-related autophagy-lysosomal alterations. These data suggest that melatonin may act to slow down the aging process because of its ability to enhance membrane fluidity and maintain structural pathways.