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Published on: July 13, 2014
Prenatal Alcohol Exposure and Transient Systemic Hypoxia-Ischemia Result in Subtle Alterations in Dendritic
Zarena M Dominguez1, Suzy Davies2, Nathaniel G Pavlik1
1Department of Pediatrics, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Insights
Prenatal alcohol exposure (PAE) and transient systemic hypoxia-ischemia (TSHI) alter medial prefrontal cortex (mPFC) neuronal morphology into adulthood. These changes may underlie neurodevelopmental deficits in executive function.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Prenatal alcohol exposure (PAE) causes neurodevelopmental deficits, including impaired executive functioning.
- Transient systemic hypoxia-ischemia (TSHI) also negatively impacts fetal growth and neurodevelopment.
- PAE is linked to an increased risk of TSHI, suggesting potential combined effects.
Purpose of the Study:
- Investigate the short-term and lasting effects of PAE and TSHI on medial prefrontal cortex (mPFC) morphology.
- Determine if PAE and TSHI interact to cause distinct patterns of injury.
- Assess lasting morphological changes in the mPFC into adulthood.
Main Methods:
- Utilized two preclinical models relevant to human development.
- Administered PAE (alcohol) or sham conditions, combined with TSHI or sham procedures.
- Examined mPFC morphology using Golgi-Cox staining and 3D Sholl analysis at postnatal days 35 and 100.
Main Results:
- TSHI significantly impacted dendritic length and branching at both time points compared to alcohol exposure alone.
- At P100, PAE and TSHI both showed insignificantly increased Sholl intersections.
- Observed enduring alterations in mPFC dendritic complexity into adulthood, with sex as a significant factor in some analyses.
Conclusions:
- PAE and TSHI induce lasting morphological changes in the adult mPFC.
- These enduring neuronal alterations may contribute to neurobehavioral deficits.
- Further research is needed to fully understand the combined impact of PAE and TSHI.
Abstract:
Prenatal alcohol exposure (PAE) is associated with long-term neurodevelopmental deficits resulting in impaired executive functioning and motor control. Intriguingly, PAE has been linked with an increased risk of transient systemic hypoxia-ischemia (TSHI), which alone results in suboptimal fetal growth and neurodevelopmental consequences. Here, using two translationally relevant preclinical models, we investigated the short-term and lasting effects of PAE and TSHI on the morphology of the medial prefrontal cortex (mPFC), a region important in executive function, and tested whether PAE interacts with TSHI to produce a distinct pattern of injury relative to either condition alone. The four experimental groups included sham (saccharin water, no TSHI), PAE (5% alcohol, no TSHI), TSHI (saccharin water, TSHI), and PAE+TSHI (5% alcohol, TSHI). Brains were extracted for Golgi-Cox staining at Postnatal Day 35 (P35) or P100 and processed for 3D Sholl analysis. The analysis of the mPFC at P35 showed no significant differences in the number of branches or dendritic length overall, although the impact of TSHI compared to alcohol was significant for both. There were no significant differences in the number of Sholl intersections overall at P35, although a sex difference was noted in PAE offspring. At P100, analysis of filament dendritic length and branching number was also significantly impacted by TSHI compared to alcohol. Interestingly, sex was also a significant factor when assessing the impact of alcohol. PAE and TSHI both had an insignificantly increased number of Sholl intersections at P100 compared to the control. The observed changes to dendritic complexity at P100 demonstrate altered neuronal morphology in the mPFC that endure into adulthood. Given the importance of the mPFC in executive functioning, these pilot data provide insight into morphological changes that may contribute to the neurobehavioral deficits observed following exposure to PAE and TSHI and highlight the need for additional investigations into this area.
