Growth hormone modulates hippocampal excitatory synaptic transmission and plasticity in old rats
ABSTRACT Alterations in the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPA-R) and N-methyl-D-aspartate receptor (NMDA-R) have been documented in aged animals and may contribute to changes in hippocampal-dependent memory. Growth hormone (GH) regulates AMPA-R and NMDA-R-dependent excitatory transmission and decreases with age. Chronic GH treatment mitigates age-related cognitive decline. An in vitro CA1 hippocampal slice preparation was used to compare hippocampal excitatory transmission and plasticity in old animals treated for 6-8 months with either saline or GH. Our findings indicate that GH treatment restores NMDA-R-dependent basal synaptic transmission in old rats to young adult levels and enhances both AMPA-R-dependent basal synaptic transmission and long-term potentiation. These alterations in synaptic function occurred in the absence of changes in presynaptic function, as measured by paired-pulse ratios, the total protein levels of AMPA-R and NMDA-R subunits or in plasma or hippocampal levels of insulin-like growth factor-I. These data suggest a direct role for GH in altering age-related changes in excitatory transmission and provide a possible cellular mechanism through which GH changes the course of cognitive decline.
SourceAvailable from: Maricela Luna[Show abstract] [Hide abstract]
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.General and Comparative Endocrinology 05/2014; 203. DOI:10.1016/j.ygcen.2014.04.035 · 2.67 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Insulin-like growth factor-I (IGF-I) is a multifunctional polypeptide and has diverse effects on brain functions. In the present study, we compared IGF-I and IGF-I receptor (IGF-IR) immunoreactivity and their protein levels between the adult (postnatal month 6) and aged (postnatal month 24) mouse hippocampus and somatosensory cortex. In the adult hippocampus, IGF-I immunoreactivity was easily observed in the pyramidal cells of the stratum pyramidale in the hippocampus proper and in the granule cells of the granule cell layer of the dentate gyrus. In the adult somatosensory cortex, IGF-I immunoreactivity was easily found in the pyramidal cells of layer V. In the aged groups, IGF-I expression was dramatically decreased in the cells. Like the change of IGF-I immunoreactivity, IGF-IR immunoreactivity in the pyramidal and granule cells of the hippocampus and in the pyramidal cells of the somatosensory cortex was also markedly decreased in the aged group. In addition, both IGF-I and IGF-IR protein levels were significantly decreased in the aged hippocampus and somatosensory cortex. These results indicate that the apparent decrease of IGF-I and IGF-IR expression in the aged mouse hippocampus and somatosensory cortex may be related to age-related changes in the aged brain.Neurochemical Research 03/2014; 39(4). DOI:10.1007/s11064-014-1269-3 · 2.55 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The diagnosis of growth hormone deficiency (GHD) in childhood is a multistep process involving clinical history, examination with detailed auxology, biochemical testing and pituitary imaging, with an increasing contribution from genetics in patients with congenital GHD. Our increasing understanding of the factors involved in the development of somatotropes and the dynamic function of the somatotrope network may explain, at least in part, the development and progression of childhood GHD in different age groups. With respect to the genetic etiology of isolated GHD (IGHD), mutations in known genes such as those encoding growth hormone (GH1), growth hormone releasing hormone receptor (GHRHR) or transcription factors involved in pituitary development, are identified in a relatively small percentage of patients suggesting the involvement of other, yet unidentified, factors. Genome wide association studies point towards an increasing number of genes involved in the control of growth, but their role in the etiology of IGHD remains unknown. Despite the many years of research in the area of GHD, there are still controversies on the etiology, diagnosis and management of isolated GHD in children. Recent data suggest that childhood IGHD may have a wider impact on the health and neurodevelopment of children, but it is yet unknown to what extent treatment with recombinant human growth hormone (rhGH) can reverse this effect. Finally the safety of rhGH is currently the subject of much debate and research and it is clear that long-term controlled studies are needed to clarify the consequences of childhood IGHD and the long-term safety of its treatment.Endocrine reviews 01/2014; 35(3):er20131067. DOI:10.1210/er.2013-1067 · 19.36 Impact Factor