Growth hormone prevents neuronal loss in the aged rat hippocampus

Abstract

Decline of growth hormone (GH) with aging is associated to memory and cognitive alterations. In this study, the number of neurons in the hilus of the dentate gyrus has been assessed in male and female Wistar rats at 3, 6, 12, 14, 18, 22 and 24 months of age, using the optical fractionator method. Male rats had more neurons than females at all the ages studied. Significant neuronal loss was observed in both sexes between 22 and 24 months of age. In a second experiment, 22 month-old male and female rats were treated for 10 weeks with 2 mg/kg/day of GH or saline. At 24 months of age, animals treated with GH had more neurons in the hilus than animals treated with saline. These findings indicate that GH is neuroprotective in old animals and that its administration may ameliorate neuronal alterations associated to aging.

Introduction

The central nervous system is a target for growth hormone (GH) actions [45]. GH deficiency is associated with sleep disturbances, memory loss, feeling of diminished well being and other cognitive impairments [5], [27], [39], [53]. Memory and cognitive performances of GH-deficient patients are ameliorated by GH replacement therapy [4], [5], [8], [9], [15], [23], [39], [53]. In animal models, GH has been shown to protect the brain and the spinal cord from different forms of neurodegenerative stimuli and promote neuronal survival after hypoxic–ischaemic injury [25], [46], [55], [56]. These neuroprotective effects of GH suggest that decreases in the hormonal levels with age [34] may affect the brain and may contribute to the aging-associated deterioration of brain function [16], [17], [20], [54].

The hippocampus, a brain region involved in spatial and episodic memory [7], may significantly contribute to aging-associated decline in cognitive abilities [43], [54]. Although in most brain areas there is no massive neuronal loss with aging [6], [10], [20], [33], [36], [40], [42], [48], [49], [50], [51], [59], [64], a significant reduction in the number of neurons has been reported in the hilus of the dentate gyrus of the hippocampal formation in aged humans [62] and in 24 month-old Fischer 344 male rats [57]. In the present study we have performed an unbiased stereological analysis to estimate the total number of neurons in the hilus, in male and female Wistar rats of different ages, to confirm the existence of a neuronal loss with age. In a second experiment, we have assessed whether the administration of GH to aged rats affects neuronal content in the hilus.