48-hour access to this article
USD $30.00
USD $30.00
Isoflurane stress induces region-specific glucocorticoid levels in neonatal mouse brain
in Journal of EndocrinologyThe profound programming effects of early life stress (ELS) on brain and behavior are thought to be primarily mediated by adrenal glucocorticoids (GCs). However, in mice, stressors are often administered between postnatal days 2 and 12 (PND2–12), during the stress hyporesponsive period (SHRP), when adrenal GC production is greatly reduced at baseline and in response to stressors. During the SHRP, specific brain regions produce GCs at baseline, but it is unknown if brain GC production increases in response to stressors. We treated mice at PND1 (pre-SHRP), PND5 (SHRP), PND9 (SHRP), and PND13 (post-SHRP) with an acute stressor (isoflurane anesthesia), vehicle control (oxygen), or neither (baseline). We measured a panel of progesterone and six GCs in the blood, hippocampus, cerebral cortex, and hypothalamus via liquid chromatography tandem mass spectrometry. At PND1, baseline corticosterone levels were high and did not increase in response to stress. At PND5, baseline corticosterone levels were very low, increases in brain corticosterone levels were greater than the increase in blood corticosterone levels, and stress had region-specific effects. At PND9, baseline corticosterone levels were low and increased similarly and moderately in response to stress. At PND13, blood corticosterone levels were higher than those at PND9, and corticosterone levels were higher in blood than in brain regions. These data illustrate the rapid and profound changes in stress physiology during neonatal development and suggest that neurosteroid production is a possible mechanism by which ELS has enduring effects on brain and behavior.
Supplementary Materials
- Supplemental Figure 1. Representative locations of punches for tissue microdissection at postnatal day 5 (PND5). Each circle represents a 1mm-diameter punch from each brain region. For simplicity of illustrating punch locations, the circles are shown approximately to scale. The PND5 brain diagram was adapted from Paxinos, et al. (2007).
- Supplemental Figure 2. No effect of Sex and no interaction between Sex and Treatment on blood, hippocampus (HPC), cerebral cortex (CC), and hypothalamus (HYP) corticosterone levels in postnatal day 5 (PND5) mice. Data are shown as mean ± SEM. n = 2-8 for all regions.
- Supplemental Figure 3. In hippocampus (HPC), cerebral cortex (CC), and hypothalamus (HYP), difference in region – blood 11-deoxycorticosterone (DOC) levels in (A) post-natal day 5 (PND5), (B) PND9, (C) PND13. Data are show as mean ± SEM. n=10 for all ages and regions.
- Supplemental Figure 4. In hippocampus (HPC), cerebral cortex (CC), and hypothalamus (HYP), difference in region – blood 11-dehydrocorticosterone (DHC) levels in (A) post-natal day 5 (PND5), (B) PND9, (C) PND13. Data are show as mean ± SEM. n=10 for all ages and regions.
- Supplemental Figure 5. The effect of isoflurane, oxygen, or neither (baseline) on corticosterone levels in blood (top) and hippocampus (HPC; bottom) at postnatal day (PND) 1, 5, 9, and 13. Within a treatment, ages with different letters are significantly different. Data were analyzed by Two-way Analysis of Variance, α=0.05. Data are shown as mean ± SEM.
- Supplemental Table 1. Total number of punches collected (bilaterally) from each brain region.
- Supplemental Table 2. Number of males and females in each group.
- Supplemental Table 3. Summary of p-values from Tukey Post-Hoc tests for Mixed-Effect’s 1 analysis of steroid levels.
- Supplemental Table 4: Summary of p-values from Tukey Post-Hoc tests for Two-Way ANOVA 1 of Region-Blood corticosterone levels.
- Supplemental Table 5: Mean and 95% CI for the isoflurane group in Tissue-Blood at PND5, 1 PND9, and PND13.
Journal of Endocrinology is committed to supporting researchers in demonstrating the impact of their articles published in the journal.
The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.
More information is on the Reasons to publish page.
| Sept 2018 onwards | Past Year | Past 30 Days | |
|---|---|---|---|
| Full Text Views | 96 | 96 | 5 |
| PDF Downloads | 109 | 109 | 10 |