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E Nieves-Martinez, Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, United States
W Sonntag, Reynolds Oklahoma Center on Aging, Oklahoma University Health Sciences Center, Oklahoma City, United States
A Wilson, Internal Medicine Section of Gerontology, Wake Forest University School of Medicine, Winston-Salem, United States
A Donahue, Internal Medicine Section of Gerontology, Wake Forest University School of Medicine, Winston-Salem, United States
D Molina, Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, United States
J Brunso-Bechtold, Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, United States
M Nicolle, Internal Medicine Section of Gerontology and the Department of Physiology and Pharmacology, Wake Forest University Medical School, Winston-Salem, United States

Michelle Nicolle, Email: mnicolle{at}wfubmc.edu

Growth hormone (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 between puberty and adulthood. 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 (COGHD). 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 were 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 from puberty to young adulthood 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 GH deficiency immediately after puberty has negative effects on learning and memory that emerge by middle-age unless prevented by GH supplementation during a 4-10 week ‘critical period’ between puberty and young adulthood.