Melatonin reduces membrane rigidity and oxidative damage in the brain of SAMP8 mice.
We evaluated the autophagy-lysosomal pathway and membrane fluidity in brain cells and mitochondrial membranes obtained from senescence-accelerated (SAMP(8)) and senescence-resistant (SAMR(1)) 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 SAMP(8) compared to SAMR(1), 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 SAMP(8) than in SAMR(1) 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.
García
J J
JJ
Department of Pharmacology and Physiology, University of Zaragoza, c) Domingo Miral s/n, 50009 Zaragoza, Spain. jjgarcia@unizar.es
Piñol-Ripoll
G
G
Martínez-Ballarín
E
E
Fuentes-Broto
L
L
Miana-Mena
F J
FJ
Venegas
C
C
Caballero
B
B
Escames
G
G
Coto-Montes
A
A
Acuña-Castroviejo
D
D
D019588:Aging, Premature / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008560:Membrane Fluidity / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*
D002401:Cathepsin B; D002402:Cathepsin D; D008550:Melatonin