Resumo

A number of studies have been carried out about maternal manipulation and its consequences in the offspring. It is known that sleep deprivation leads to many physiological alterations, which could result in other consequences if it happens during pregnancy. In addition, different kinds of stress during pregnancy have already been related to the development of neurological diseases in the offspring. It has been hypothesized that sleep deprivation represents an oxidative challenge for the brain and that sleep may have a protective role against oxidative damage. Oxidative stress has been involved in the mechanisms of aging, neurodegenerative disorders and other diseases. In experimental animals, sleep deprivation increases the levels of amyloid β(Aβ) peptide in brain extracellular space, a critical event in the pathogenesis of Alzheimer disease (AD). The amyloid β(Aβ) derives from proteolysis of a large membrane spanning precursor protein, the amyloid precursor protein (APP). Presenilin-1 (PS1) and presenilin-2 (PS2) are subunits that cleave APP within the transmembrane domain generating Aβ peptides. Since presenilin expression is elevated in sleep deprived mice (unpublished data for our lab), our objective was to analyze developmental programming effects of maternal sleep deprivation on PS1 and PS2 expression in the hypothalamus of male offspring. Pregnant Swiss 3 months-old mice were distributed into 2 groups: one group was continuously sleep deprived using the multiple platforms method from gestational days 0 to 3 (PSD 72), and the other group was allowed to sleep normally during pregnancy (CT). At the 3rd month of age, male offspring (n, PSD 72=6; CT=6) was euthanized by decapitation, the hypothalamus was harvested and mRNA isolated by Trizol® method. PS1 and PS2 mRNA expression were quantified by real time PCR using GAPDH as the housekeeping gene. Our results demonstrate that PS1 and PS2 expression decreases 16% and 34% respectively in offspring of sleep-deprived mothers when compared to controls (p<0.05). Considering these results, we can speculate that sleep deprivation during pregnancy can reduce amyloid plaque formation in response to decreased expression of PS1 and PS2 which, in turn, could have a protective effect for Azheimer’s disease in offspring.