Early-onset GH deficiency results in spatial memory impairment in mid-life and is prevented by GH supplementation

Abstract

GH levels increase to high concentrations immediately before puberty then progressively decline with age. GH deficiency (GHD) originating in childhood is treated with GH supplementation to foster somatic development during adolescence. It is not clear if or how early GH replacement affects memory in adulthood, or whether it can prevent the cognitive deficits commonly observed in adults with childhood-onset GHD. Rats homozygous for the Dw-4 mutation (dwarf) do not exhibit the normal increase in GH at 4 weeks of age when GH levels normally rise and are used to model childhood or early-onset GHD (EOGHD). One group of these rats was injected with GH from 4 to 14 weeks of age to model GH supplementation during adolescence with GHD beginning in adulthood (adult-onset GHD; AOGHD). Another group received GH from 4 weeks throughout the lifespan to model normal lifespan GH (GH-replete). Age-matched, Dw-4 heterozygous rats (HZ) do not express the dwarf phenotype and were used as controls. At 8 and 18 months of age, spatial learning in the water maze was assessed. At 8 months of age all experimental groups were equally proficient. However, at 18 months of age, the EOGHD group had poor spatial learning compared to the AOGHD, GH-replete, and HZ groups. Our data indicate that GHD during adolescence has negative effects on learning and memory that emerge by middle-age unless prevented by GH supplementation.

Beneficial Effects of Growth Hormone Treatment on Cognition in Children with Prader-Willi Syndrome: A Randomized Controlled Trial and Longitudinal Study

“…This is in line with other studies showing that GH treatment can influence spatial skills. In GH-deficient adults, GH treatment prevented spatial memory impairment (25), and in hypophysectomized rats, spatial performance was significantly better in GH-treated than in untreated animals (26).…”

IGF‐1 deficiency impairs neurovascular coupling in mice: implications for cerebromicrovascular aging

“…Previous studies using the Morris water maze (Trejo et al ., 2007) and the Barnes maze (Sonntag and Csiszar, unpublished data, 2012) also yielded similar results, showing that IGF‐1‐deficient mice exhibit impaired spatial working memory. Learning and/or memory deficits were also observed in GH/IGF‐1‐deficient Lewis dwarf rats (Nieves‐Martinez et al ., 2010), spontaneously dwarf SD rats (Li et al ., 2011), and in Ames dwarf mice in some (Derenne et al ., 2011), but not all (Sharma et al ., 2010), studies.…”

IGF-1 deficiency in a critical period early in life influences the vascular aging phenotype in mice by altering miRNA-mediated post-transcriptional gene regulation: implications for the developmental origins of health and disease hypothesis

“…In mammals, the loss of insulin signaling during development is lethal. In recent years, the concept has emerged that alterations in developmental IGF-1 levels in mammals can also regulate aging processes, conferring both antiand pro-aging effects later in life in an organ systemspecific manner (Leiser and Miller 2010;Maynard and Miller 2006;Murakami et al 2003;Nieves-Martinez et al 2010;Page et al 2009;Panici et al 2010;Ramsey et al 2002;Sadagurski et al 2015;Salmon et al 2005;Sonntag et al 2005a;Ungvari et al 2010Ungvari et al , 2011Wang Fig. 2 Changes in miRNA expression profile in aortas associated with developmental IGF-1 deficiency and aging.…”