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Topic

Elucidating the Mechanisms Underlying Fetal Alcohol Spectrum Disorders and Therapeutics: The Effects of Postnatal Choline Supplementation and Exercise Intervention on Cellular Proliferation in the Neurogenic Niche of the Hippocampus

Division of Medical Sciences

Date & location

• Thursday, December 12, 2024
• 9:00 A.M.
• Virtual Defence

Examining Committee

Supervisory Committee

• Dr. Brian Christie, Division of Medical Sciences, University of Victoria (Supervisor)
• Dr. Jennifer Thomas, Department of Psychology, San Diego State University (Outside Member)

External Examiner

• Dr. Hector Caruncho, Division of Medical Sciences, UVic

Chair of Oral Examination

• Dr. Terri Lacourse, Department of Biology, UVic

Abstract

Alcohol exposure to a developing fetus can produce a wide variety of deleterious and transient effects; these effects present as a collection of symptoms and in clinical populations, are referred to as Fetal Alcohol Spectrum Disorders (FASDs). With prevalence rates of around 7 in 1000 cases, globally, FASDs are among the leading causes of neurodevelopmental damage. The amount and timing of alcohol use are factors that play into the severity and type of damage seen in patients with an FASD. Symptom types can range from craniofacial abnormalities to central nervous system (CNS) dysfunction. The third trimester of fetal development contains a growth spurt for the hippocampus, a region of the brain responsible for learning and memory processes and during this time, it is particularly susceptible to teratogenic insult. Additionally, the hippocampus contains one of the few neurogenic niches in the peri-adolescent brain, within the subgranular zone (SGZ) of the dentate gyrus (DG). As a result, it is expected that alcohol exposure during this period will disrupt neurogenic processes, but whether this effect is transient remains unclear. In recent years, professionals have moved towards novel approaches for the treatment of FASDs involving choline and aerobic exercise as effective treatment options; research is ongoing. Choline is an essential nutrient that plays a vital role in many neural and bodily processes including cell membrane synthesis, methylation, and neurotransmission. Aerobic exercise involves sustained, rhythmic physical activity and improves cardiovascular endurance through an increase in heart rate and oxygen flow to muscles. Previous work has demonstrated choline as an effective treatment to counter the aberrant effects of prenatal alcohol exposure (PAE) on the developing brain, particularly in hippocampal-dependent behaviours and similarly, it has been reported that aerobic exercise can enhance neurogenesis in the hippocampus and counteract deficits caused by PAE. To determine the effects of each of these treatments on the first stage of neurogenesis, cellular proliferation, a postnatal binge model of ethanol exposure with postnatal choline supplementation and juvenile chronic moderately-paced forced running was employed, and animals were sacrificed during the peri-adolescent period (PD36). Corresponding tissue was subject to immunohistological staining against bromodeoxyuridine (BrdU) and Ki67, and cell-positive densities for each stain were determined. Results showed no significant variations in the densities of proliferating cells of any treatment (ethanol exposure or choline supplementation) except forced running, which showed significant increases in Ki67 cell densities only. Similarly, two-way combinations of treatments and all three treatments showed no significant differences. Although this study provides insight into the relationship between hippocampal neurogenesis and ethanol, choline, and aerobic exercise, it is limited by methodological constraints which may influence the generalizability of the findings.