Objective: 

It has been suggested that the age-related decrease in the number of neurons in the hippocampus that leads to learning and memory alterations may be associated with apoptosis.

Methods: 

Twenty-four male Wistar rats of 22 months of age were divided into three groups. One group remained untreated and acted as the control group. The second was treated with growth hormone (GH) for 10 weeks (2 mg/kg/d sc) and the third was submitted to melatonin treatment (1 mg/kg/d) in the drinking water for the same time. A group of 2-months-old male rats was used as young controls. All rats were killed by decapitation at 24.5 month of age. Levels of HSP70 were analysed by ELISA. The expression of pro-apoptotic markers like Bax, Bad, AIF and anti-apoptotic Bcl2, NIAP, XIAP, SIRT 1 and 2 genes were determined by RT-PCR. The protein expressions of Bax, Bad, Bcl-2 and MCL-1 were also studied by Western blot.

Results: 

Aging was associated with an increase in apoptosis promoting markers and with the reduction of some anti-apoptotic ones. Expressions of SIRT1 and SIRT2 as well as levels of HSP70 were decreased in hippocampus of old rats. GH treatment was able to reduce the pro/anti-apoptotic ratio to levels observed in young animals and to increase SIRT2. Melatonin reduced also expression of pro-apoptotic genes and proteins, and increased levels of MCL-1 proteins and SIRT1.

Conclusions: 

We have demonstrated that melatonin and growth hormone can modulate the pro-antiapoptotic ratio and increase sirtuins expression. Our data demonstrated that melatonin and growth hormone could exert a protective effect on hippocampal damage induced by aging.