Alzheimer’s disease (AD) is a primary cause of dementia in the elderly. It is determined by the deposits of Aβ which leads to memory impairment, oxidative stress associated to a deficient
antioxidant defense system. AD patients also show alterations in their circadian rhythms. Numerous studies have shown that Pioglitazone (Pio) possess antioxidant properties and Valproic Acid (VA)
improved cognitive deficits in an experimental model of AD. Taking into account these observations,
the objective of this study was to evaluate the effect of Pio/VA, on the 24h rhythms of lipid
peroxidation, as well as on catalase (CAT) and glutathione peroxidase (GPx) expression and activity
and Bdnf/TrkB expression in the hippocampus of Aβ-injected rats. Four-month-old males Holtzman
rats were divided into three groups defined as: 1) control 2) Aβ-injected 3) Aβ-injected treated with
Pio-VA. Rats were maintained under 12h-Light:12h-Dark conditions. Lipid peroxidation levels were
determined by colorimetric assays and CAT and GPx enzymatic activities by kinetic assays. CAT, GPx
and Bdnf/TrkB transcript levels were determined by RT-PCR in hippocampus samples isolated every 6
h. We found that the treatment of Pio-VA reestablished rhythmicity of those temporal patterns. These
findings might constitute, at least in part, molecular and biochemical basis of restoration of circadian
rhythmicity by the administration of Pio-VA in neurodegenerative disorders.