Running in mice increases the expression of brain hemoglobin-related genes interacting with the GH/IGF-1 system

Abstract

The beneficial effects of exercise are partly mediated via local or systemic functions of the insulin-like growth factor-1 (IGF-1) system. As IGF-1 increases local brain hemoglobin beta (Hbb) transcripts, we hypothesized that exercise could have similar effects. Mice were single-housed with free access to running wheels for seven days. After sacrifice and saline perfusion, the expression of 13 genes was quantified using real-time quantitative polymerase chain reaction (RT-qPCR) in three brain regions: the prefrontal cortex, motor cortex, and hippocampus. In addition, plasma insulin, glucose, homeostatic model assessment of IR (HOMA-IR), C-peptide, and IGF-1 were investigated. We show that hemoglobin-related transcripts (Hbb and 5'-aminolevulinate synthase 2 [Alas2]) increased 46-63% in the running group, while IGF-1-related genes [Igf1 / growth hormone receptor (Ghr)] decreased slightly (7%). There were also moderate to large correlations between Hbb- and IGF-1-related genes in the running group but not in the sedentary group. HOMA-IR, plasma glucose, and insulin changed marginally and non-significantly, but there was a trend toward an increase in plasma-IGF-1 in the running group. In conclusion, seven days of running increased Hbb-related transcripts in three brain regions. Hbb-related transcripts correlated with components of the brain IGF-1 system only in the running group.

Keywords: Brain; Exercise; Insulin resistance; Insulin-like growth factor-1; Rodent; Sedentary.

Fig. 1

This Figure visually shows the levels of each transcript also shown in Tables 3 to facilitate comprehension of the pattern of changes in the specific brain regions and aggregates of the three brain regions. Total transcript levels for all three brain regions (prefrontal cortex, hippocampus, and motor cortex) are shown for runners as percentage vs. sedentary animals. Transcript levels have been normalized to Gapdh. Sedentary levels = 100%. Data is presented as mean ± 95% Cl. Individual transcript comparisons in each brain region are made with t-tests, and aggregated effects (brackets) in the three brain regions are made with mixed models (see Methods). *P < 0.05, ***P < 0.001, or t-test, ^§P < 0.05, were used for statistical comparison as described in Methods.

Fig. 2

Levels of categories of transcripts in all brain regions (prefrontal cortex, hippocampus, and motor cortex). Aggregated comparisons are made with mixed model analysis, as described in Methods (statistical analysis). Sedentary levels = 100%. Data are presented as means ± 95% confidence intervals, **P < 0.01.