Growth hormone (GH), brain development and neural stem cells

Queensland Brain Institute and Institute for Molecular Bioscience, University of Queensland, St Lucia, Australia 4072.
Pediatric endocrinology reviews: PER 12/2011; 9(2):549-53.
Source: PubMed


A range of observations support a role for GH in development and function of the brain. These include altered brain structure in GH receptor null mice, and impaired cognition in GH deficient rodents and in a subgroup of GH receptor defective patients (Laron dwarfs). GH has been shown to alter neurogenesis, myelin synthesis and dendritic branching, and both the GH receptor and GH itself are expressed widely in the brain. We have found a population of neural stem cells which are activated by GH infusion, and which give rise to neurons in mice. These stem cells are activated by voluntary exercise in a GH-dependent manner. Given the findings that local synthesis of GH occurs in the hippocampus in response to a memory task, and that GH replacement improves memory and cognition in rodents and humans, these new observations warrant a reappraisal of the clinical importance of GH replacement in GH deficient states.

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    • "Endocrinol . (2014), neurons in mice (Waters and Blackmore, 2011). A number of reports have shown that GH administration following injury confers neuroprotection and accelerates the recovery of some neural functions and may play a role in brain repair (Arce et al., 2013; Devesa et al., 2013). "
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    ABSTRACT: There is increasing evidence that growth hormone (GH) expression is not confined exclusively to the pituitary somatotrophs as it is synthesized in many extrapituitary locations. The nervous system is one of those extrapituitary sites. In this brief review we summarize data that substantiate the expression, distribution and characterization of neural GH and detail its roles in neural function, including cellular growth, proliferation, differentiation, neuroprotection and survival, as well as its functional roles in behavior, cognition and neurotransmission. Although systemic GH may exert some of these effects, it is increasingly evident that locally expressed neural GH, acting through intracrine, autocrine or paracrine mechanisms, may also be causally involved as a neurotrophic factor.
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    ABSTRACT: Stem cells maintain their self-renewal and multipotency capacities through a self-organizing network of transcription factors and intracellular pathways activated by extracellular signaling from the microenvironment or "niche" in which they reside in vivo. In the adult mammalian brain new neurons continue to be generated throughout life of the organisms and this lifelong process of neurogenesis is supported by a reservoir of neural stem cells in the germinal regions. The discovery of the lifelong neurogenesis in the mammalian adult brain has sparked great interest in defining the conditions that guide neural stem cell (NSC) maintenance and differentiation into the great variety of neuronal and glial subtypes. Here we review current knowledge regarding the paracrine regulation provided by the components of the niche and its function, focusing on the main germinal region of the adult central nervous system (CNS), the subependymal zone (SEZ).
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    ABSTRACT: A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GH treatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anaesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups. Animal group treated with GH immediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls. GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion. Early GH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GH effects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area).
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