Changes in oxidative stress parameters and neurodegeneration markers in the brain of the senescence-accelerated mice SAMP-8.
The senescence-accelerated strains of mice (SAMP) are well-characterized animal models of senescence. Senescence may be related to enhanced production or defective control of reactive oxygen species, which lead to neuronal damage. Therefore, the activity of various oxidative-stress related enzymes was determined in the cortex of 5 months-old senescence-accelerated mice prone-8 (SAMP-8) of both sexes and compared with senescence-accelerated mice-resistant-1 (SAMR-1). Glutathione reductase and peroxidase activities in SAMP-8 male mice were lower than in male SAMR-1, and a decreased catalase activity was found in both male and female SAMP-8 mice, which correlates with the lower catalase expression found by Western blotting. Nissl staining showed marked loss of neuronal cells in the cerebral cortex of five month-old SAMP-8 mice. SAMP-8 mice also had marked astrogliosis and microgliosis. We also found an increase in caspase-3 and calpain activity in the cortex. In addition, we observed morphological changes in the immunostaining of tau protein in SAMP-8, indicative of a loss of their structural function. Altogether, these results show that, at as early as 5 months of age, SAMP-8 mice have cytological and molecular alterations indicative of neurodegeneration in the cerebral cortex and suggestive of altered control of the production of oxidative species and hyper-activation of calcium-dependent enzymes.
Unitat de Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, c./St. Llorenç 21, E-43201 Reus, Tarragona, Spain. francesc.sureda@urv.net
Francesc X
FX
Sureda
Javier
J
Gutierrez-Cuesta
Marta
M
Romeu
Miquel
M
Mulero
Anna Maria
AM
Canudas
Antoni
A
Camins
Jordi
J
Mallol
Mercè
M
Pallàs
D019588:Aging, Premature / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D002154:Calpain / Q000032:analysis / Q000378:metabolism; D002374:Catalase / Q000032:analysis / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000032:analysis / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D005979:Glutathione Peroxidase / Q000032:analysis / Q000378:metabolism; D005980:Glutathione Reductase / Q000032:analysis / Q000378:metabolism; D005982:Glutathione Transferase / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D010766:Phosphorylation; D012737:Sex Factors; D016875:tau Proteins / Q000378:metabolism
D015415:Biomarkers; D016875:tau Proteins; D002374:Catalase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D051360:Cyclin-Dependent Kinase 5; D002154:Calpain; D003546:Cysteine Endopeptidases