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

• Published in: Neurobiology of aging Vol. 32; no. 11; pp. 2045 - 2054
• Main Authors: García, J.J., Piñol-Ripoll, G., Martínez-Ballarín, E., Fuentes-Broto, L., Miana-Mena, F.J., Venegas, C., Caballero, B., Escames, G., Coto-Montes, A., Acuña-Castroviejo, D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2011
• Subjects: Aging; Aging, Premature - metabolism; Animals; Brain - drug effects; Brain - metabolism; Cathepsin B - metabolism; Cathepsin D - metabolism; Cell Membrane - drug effects; Cell Membrane - metabolism; Female; Internal Medicine; Male; Melatonin; Melatonin - pharmacology; Membrane fluidity; Membrane Fluidity - drug effects; Mice; Mice, Transgenic; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Neurology; Oxidative stress; Oxidative Stress - drug effects; Senescence-accelerated mice; Aging; Oxidative stress; Senescence-accelerated mice; Melatonin; Membrane fluidity; Mitochondria
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2009.12.013

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.