Early-onset GH deficiency results in spatial memory impairment in mid-life and is prevented by GH supplementation
Early-onset GH deficiency results in spatial memory impairment in mid-life and is prevented by GH supplementation
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DOI：
10.1677/joe-09-0323
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Nicolle, M. M.
中科院分区：
文献类型：
--
作者：
Nieves-Martinez, E.;Sonntag, W. E.;Nicolle, M. M.
生长激素水平在青春期前立即升高到高浓度，然后随着年龄的增长逐渐下降。生长激素缺乏症（GHD）起源于儿童是治疗与生长激素补充，以促进体细胞发育在青春期。目前尚不清楚早期生长激素替代是否或如何影响成年期的记忆，也不清楚它是否能预防儿童期发病的成人GHD中常见的认知缺陷。Dw-4突变纯合的大鼠（侏儒）在4周龄时没有表现出正常的生长激素增加，而生长激素水平通常会上升，并被用来模拟儿童或早发性GHD（EOGHD）。其中一组大鼠在4周龄至14周龄注射生长激素，以模拟成年期开始的GHD（成人型GHD； AOGHD）在青春期补充生长激素。另一组在整个生命周期中从4周开始接受GH治疗，以模拟正常寿命GH （GH- full）。年龄匹配的Dw-4杂合大鼠（HZ）不表达侏儒表型，并作为对照。在8个月和18个月大时，对水迷宫中的空间学习进行评估。在8个月大时，所有实验组的熟练程度相同。然而，在18个月大时，与AOGHD、gh - full和HZ组相比，EOGHD组的空间学习能力较差。我们的数据表明，青春期的GHD对学习和记忆有负面影响，除非通过补充生长激素来预防，否则这种影响会在中年时出现。内分泌学杂志（2010）204,31-36
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 child-hood-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. Journal of Endocrinology (2010) 204, 31-36