Prenatal Alcohol Exposure and Placental Insufficiency Results in Reduced Neuronal Complexity in the Rat Prefrontal Cortex

Nathaniel Pavlik, Department of Pediatrics
Jessie Newville, Department of Neurosciences
Clement P. Jose, University of New Mexico SOM
Suzy Davies, Department of Neurosciences
Jennifer Wagner, Department of Neurosciences
Jonathan L. Brigman, Department of Neurosciences
Daniel D. Savage, Department of Neurosciences
Jessie R. Maxwell, Department of Pediatrics, Department of Neurosciences

Presented at the Annual Pediatric Research Forum Poster session. Contact Jessie Maxwell JRMaxwell@salud.unm.edu for questions.

Abstract

Prenatal Alcohol Exposure (PAE) can produce long-term neurodevelopmental deficits and impaired executive function. Alcohol exposure during gestation is associated with impaired fetal development caused by placental insufficiency. The impact following PAE and placental insufficiency (PI) remains unknown. Utilizing a three-dimensional (3D) Sholl analysis, we hypothesized that PAE+PI will result in decreased neuronal complexity within the frontal cortex, a region critical to executive functioning. Pregnant Long-Evans rats voluntarily drank 5% ethanol or saccharin water until embryonic day 18 (E18) to mimic moderate PAE. On E19, a laparotomy was performed to occlude the uterine artery for 60 minutes to induce PI. The pups delivered normally. At postnatal day 100 (P100), brains were extracted and Golgi-Cox stained. Coronal sections were imaged utilizing a Leica TCS SP8 Confocal microscope with z-stacking capabilities. A 3D Sholl analysis was conducted within Imaris software to assess variance in neural complexity between treatment groups. Analysis was completed with a 2-way ANOVA and t-test. Five PAE+PI and 5 control brains were collected. In the medial frontal cortex, 3 neurons were analyzed from each hemisphere. No statistical difference was noted between the two hemispheres, so the data was combined for each animal resulting in 6 neurons being analyzed. The proximal dendritic complexity was similar between groups. PAE+PI resulted in significantly diminished complexity more distal from the soma; at 80 m the PAE+PI group had an average of 2.4 intersections while the control group had an average of 3.3 (p<0.05). At 90 m, the PAE+PI group continued to have fewer intersections compared to controls (1.8 vs. 2.6). This is the first study to investigate the dendritic complexity following PAE combined with PI within the frontal cortex. Given the importance of this region to executive function, this may provide insight into the long-term deficits that are observed and provide support for interventions.