Growth hormone increases neural cell adhesion polysialylation state in the dentate gyrus of γ-irradiated rats

Abstract

Prenatal irradiation has severe consequences in the central nervous system (CNS), ranging from microcephaly and subcortical heteropia to cognitive dysfunction in rodents (Schull and Otake,1991; Schull et al.,1990). Radiation exposure induces cerebral cortex malformation, mental retardation, and attention deficit-hyperactivity disorders in humans (Mizumatsu et al.,2003; Monje,2008; Schull and Otake,1991; Schull et al.,1990); in adult γ-irradiated rats, it causes memory impairment (Sienkiewicz et al.,1994). Neural cell adhesion molecule (NCAM) is the major carrier of 2,8-linked sialic acid residues (PSA), which are only present in regions of synaptic plasticity and permanent neurogenesis in the adult rat brain. NCAM is involved in synaptogenesis, neuroprotection, axonal sprouting and, memory formation (Cremer et al.,2000; Merino et al.,2000). Polysialic acid (PSA) is a posttranslational modification of NCAM that promotes plasticity and allows structural remodeling in the brain (Kiss and Rougon,1997). Different products have been used against the detrimental effects of gamma radiation in rodents, including growth hormone (GH) (Gómez de Segura et al.,1998; Madrid et al.,2002). Several studies have identified GH-receptors in the hippocampus and the prefrontal cortex (Lobie et al.,1993; Zhai et al.,1994). The pleiotropic actions of GH in the CNS range from neuroprotection, neurogenesis (Scheepens et al.,2001), axonal elongation, and dendritic arborization, to neuronal migration, and it can reduce cognitive impairment (Aberg et al.,2000; Muresanu et al.,2006; Sienkiewicz et al.,2000). Because these brain processes are regulated by PSA-NCAM and hormones, including GH, we wanted to ascertain whether PSA-NCAM might be a target for GH effects in the dentate gyrus of γ-irradiated rats. Few studies have investigated the relationship between cell adhesion molecules and the effect of GH in the hippocampus of γ-irradiated rats (Hienz et al.,2008). The possibility that GH induces remodelatory effects and/or lessens cell death in the hippocampus of γ-irradiated rats through a regulation of PSA-NCAM protein levels has not been investigated. To answer these questions, we evaluated PSA-NCAM levels by immunofluorescence and CXCR4 by immunoblot in the hippocampus of γ-irradiated either treated or not treated with GH. We also analyzed whether GH exerts antioxidant effects on SOD-2-Mitochondrial Superoxide Dismutase 2-dependent levels as well as whether GH might regulate CXCR4 protein levels in the hippocampus of γ-irradiated rats.