Circulating insulin-like growth factor (IGF)-1 Regulates Hippocampal IGF-1 Levels and Brain Gene Expression During Adolescence

ABSTRACT: This study, using a growth hormone (GH)-deficient dwarf animal model and peripheral GH replacement, investigated the effects of circulating IGF-1 during adolescence on IGF-1 levels in the brain. Our results demonstrated that hippocampal IGF-1 protein concentrations during adolescence are highly regulated by circulating IGF-1, which were reduced by GH deficiency and restored by systematic GH replacement. In contrast, IGF-1 levels in the CSF were decreased by GH deficiency but not restored by GH replacement. Furthermore, analysis of gene expression using microarrays and RT-PCR indicated that circulating IGF-1 levels did not modify the transcription of IGF-1 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. GH-deficient dwarf (dw/dw) and heterozygous (HZ) rats were identified at postnatal day 33-34. Starting from d35, dw/dw rats received subcutaneous injection of either 300µg GH (dw/dw+GH) or saline (dw/dw+sal) for 7d or 30d. HZ animals received saline for the same periods as controls. Animals (n=4/group for each time point) were sacrificed, the hippocampi were dissected, and total RNA were isolated for subsequent transcriptomic profiling.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Robert Brucklacher 

PROVIDER: E-GEOD-29512 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress