The growth hormone secretagogue hexarelin increases cell proliferation in neurogenic regions of the mouse hippocampus

Objective: Radiation therapy (RT) to the brain is often used in the treatment of children with different types of malignant diseases affecting the brain. However, RT in childhood may also have severe side effects including impaired brain maturation and intellectual development. For childhood cancer survivors these adverse effects of RT can Cause lifelong disability and suffering. Therefore, there is an unmet need to limit late effects after RT. Precursor cells in the subgranular zone of the dentate gyrus (DG) in the hippocampus are particularly sensitive to irradiation (IR). This may be of significance as newly generated neurons in the DG are important for memory and learning. GH secretagogues (GHS) have previously been shown to promote neurogenesis and to have neuroprotective effects. In addition, several parts of the brain, including the hippocampus, have been shown to express the GHS receptor la (GHS-R1a). The aim of this Study was to evaluate the potential effect of the GHS hexarelin on proliferation and survival of progenitor cells in the hippocampus after brain IR in a mouse model. Design: In the present study, 10-day-old male mice received 6 Gy cranial IR. Non-irradiated sham animals were used as controls. We treated one group of irradiated and one sham group with hexarelin (100 mu g/kg/day) for 28 days and used immunohistochemical labeling of bromo-deoxy uridine (BrdU) and phosphohistone H3 of the granular cell layer of the DG to evaluate proliferation and cell survival after IR at postnatal day ten. Results: Our results show that hexarelin significantly increased the number of BrdU-positive cells in the granule cell layer by approximately 50% compared to controls. Conclusion: The increased number of BrdU-positive cells in the granule cell layer suggests a partial restoration in the pool of proliferating cells by hexarelin after IR. (C) 2009 Elsevier Ltd. All rights reserved.