Circulating IGF1 regulates hippocampal IGF1 levels and brain gene expression during adolescence

被引:57
|
作者
Yan, Han [1 ]
Mitschelen, Matthew [1 ]
Bixler, Georgina V. [2 ]
Brucklacher, Robert M. [2 ]
Farley, Julie A. [1 ]
Han, Song [1 ]
Freeman, Willard M. [2 ]
Sonntag, William E. [1 ]
机构
[1] Univ Oklahoma, Hlth Sci Ctr, Reynolds Oklahoma Ctr Aging, Donald W Reynolds Dept Geriatr Med, Oklahoma City, OK 73104 USA
[2] Penn State Coll Med, Genome Sci Facil, Hershey, PA 17033 USA
关键词
GROWTH-FACTOR-I; QUALITY-OF-LIFE; HORMONE DEFICIENT PATIENTS; GH REPLACEMENT THERAPY; FOR-GESTATIONAL-AGE; CEREBRAL BLOOD-FLOW; COGNITIVE FUNCTION; CEREBROSPINAL-FLUID; OXIDATIVE STRESS; RAT HIPPOCAMPUS;
D O I
10.1530/JOE-11-0200
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
GH and its anabolic mediator, IGF1, are important not only in somatic growth but also in the regulation of brain function. Even though GH treatment has been used clinically to improve body composition and exercise capacity in adults, its influence on central nervous system function has only recently been recognized. This is also the case for children with childhood-onset GH deficiency (GHD) where GH has been used to stimulate bone growth and enhance final adult height. Circulating IGF1 is transported across the blood-brain barrier and IGF1 and its receptors are also synthesized in the brain by neurons and glial and endothelial cells. Nevertheless, the relationship between circulating IGF1 and brain IGF1 remains unclear. This study, using a GH-deficient dwarf rat model and peripheral GH replacement, investigated the effects of circulating IGF1 during adolescence on IGF1 levels in the brain. Our results demonstrated that hippocampal IGF1 protein concentrations during adolescence are highly regulated by circulating IGF1, which were reduced by GHD and restored by systematic GH replacement. Importantly, IGF1 levels in the cerebrospinal fluid were decreased by GHD but not restored by GH replacement. Furthermore, analysis of gene expression using microarrays and RT-PCR indicated that circulating IGF1 levels did not modify the transcription of Igf1 or its receptor in the hippocampus but did regulate genes that are involved in microvascular structure and function, brain development, and synaptic plasticity, which potentially support brain structures involved in cognitive function during this important developmental period. Journal of Endocrinology (2011) 211, 27-37
引用
收藏
页码:27 / 37
页数:11
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