Growth hormone and melatonin prevent age-related alteration in apoptosis processes in the dentate gyrus of male rats

R A Kireev,J A F Tresguerres,E Vara

doi:10.1007/s10522-013-9443-6

R A Kireev, J A F Tresguerres + Show 1 more

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https://doi.org/10.1007/s10522-013-9443-6

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Journal: Biogerontology	Publication Date: Jul 13, 2013
Citations: 79	License type: CC BY 2.0

Affiliation: Universidad Complutense de Madrid

Abstract

It has been suggested that the age-related decrease in the number of neurons in the hippocampus that leads to alterations in brain function, may be associated with an increase in apoptosis due to the reduced secretion of growth hormone (GH) and/or melatonin in old animals. In order to investigate this possibility, 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 (hGH) for 10 weeks (2 mg/kg/d sc) and the third was subjected 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 more than 24 month of age and dentate gyri of the hippocampi were collected. Aging in the dentate gyrus was associated with an increase in apoptosis promoting markers (Bax, Bad and AIF) and with the reduction of some anti-apoptotic ones (XIAP, NIAP, Mcl-1). Expressions of sirtuin 1 and 2 (SIRT1 and 2) as well as levels of HSP 70 were decreased in the dentate gyrus of old rats. GH treatment was able to reduce the pro/anti-apoptotic ratio to levels observed in young animals and also to increase SIRT2. Melatonin reduced also expression of pro-apoptotic genes and proteins (Bax, Bad and AIF), and increased levels of myeloid cell leukemia-1 proteins and SIRT1. Both treatments were able to reduce apoptosis and to enhance survival markers in this part of the hippocampus.

Highlights

The hippocampus is a target of age-related physiological and structural changes
The B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio was higher in the group of young animals as compared to old and treatment with growth hormone (GH) and melatonin were able to increase this parameter, showing that cells in this area of the hippocampus were protected from apoptosis
We have demonstrated that aging induced significant increases in gene and protein expressions of pro-apoptotic markers (Bax and Bcl-2-associated death promoter (Bad)) in the dentate gyrus of male rats

Summary

Introduction

The hippocampus is a target of age-related physiological and structural changes. Alterations in the hippocampus during aging are paralleled by behavioral and functional deficits in hippocampus-dependent learning and memory tasks (Rosenzweig and Barnes 2003). It has been suggested that the decrease in the number of neurons by apoptosis may be associated with trophic factor(s) deprivation (Ambacher et al 2012) or with the absence or reduction of anti-apoptotic proteins such as B-cell lymphoma 2 (Bcl-2) (Allsopp et al 1993). Many apoptosis-related factors have been demonstrated to be up-regulated in the immature brain, such as caspase-3, Apaf-1 and Bcl-2-associated X protein (Bax) (Ota et al 2002; Troy et al 2011). NIAP directly inhibits caspase-3, -7, and -9 and XIAP directly inhibits caspase-3 and caspase-7 (Prunell and Troy 2004)

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