Prenatal Exposure to Cannabinoids Decreases the Expression of Polysialylated-Neural Cell Adhesion Molecule (PSA-NCAM)

Abstract

The use of cannabis during pregnancy has continued to rise in recent years despite recent studies in humans showing that prenatal exposure can elicit developmental delays and long-lasting cognitive deficits. Using a rodent model, this preclinical study investigates the consequences of prenatal cannabis exposure to Delta-9-tetrahydrocannabinol (THC) on offspring development, including the day of fur development and eye-opening, spontaneous righting reflex on postnatal days 5, 8 or 11 and rate of bodyweight gain. We also examined the protein expression of Neural Cell Adhesion Molecule (NCAM) and Polysialylated-NCAM (PSA-NCAM), which is required for neurogenesis, neuronal pathfinding, learning and memory and has been shown in our previous studies to be linked to synaptic plasticity deficits in offspring exposed to a cannabinoid agonist prenatally. THC- exposed offspring did not differ on the day of fur development and eye-opening. Spontaneous right reflex was significantly shorter on postnatal day 5 but returned to that of vehicle-exposed pups on postnatal days 8 and 11. Bodyweight was slightly decreased for THC-exposed offspring during early development but did not differ from vehicle-exposed offspring by postnatal day 45. THC-exposed offspring exhibited reduced hippocampal protein expression of PSA-NCAM during adolescence. These findings suggest prenatal exposure to THC can have long-term detrimental effects on the expression of PSA attached to NCAM, which is developmentally regulated and may provide one possible mechanism for the cognitive deficits associated with prenatal cannabinoid exposure.

Keywords: Prenatal; Cannabinoid; Developmental; Glutamate; Marijuana; Adolescence; Cannabis

Abbreviations: THC: Delta-9-tetrahydrocannabinol; NCAM: Neural Cell Adhesion Molecule; PSA-NCAM: Polysialylated- NCAM; PCE: Prenatal Cannabinoid Exposure; LTP: Long-Term Potentiation; GD: Gestational Day; PND: Postnatal Day.