Early-onset GH deficiency results in spatial memory impairment in mid-life and is prevented by GH supplementation.
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.
Nieves-Martinez
E
E
Neuroscience Program, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157-1083, USA.
Sonntag
W E
WE
Wilson
A
A
Donahue
A
A
Molina
D P
DP
Brunso-Bechtold
J
J
Nicolle
M M
MM
D000375:Aging / Q000097:blood / Q000523:psychology*; D000818:Animals; D030801:Animals, Genetically Modified; D001835:Body Weight; D013006:Growth Hormone / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology* / Q000517:prevention & control*; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D013550:Swimming; D013552:Swine
D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone