HIPPOCAMPAL ALTERATIONS AND COGNITIVE IMPAIRMENT IN SWISS ALBINO MICE EXPOSED TO PRENATAL ZIDOVUDINE

Abstract

Introduction: Exposure to drugs in utero may induce developmental alterations,
including impaired growth, birth defects, and altered brain development. Zidovudine
(ZDV) with a chemical name AZT, is a thymidine analog, exhibits teratogenic and
neurotoxic effects. Nevertheless, it remains an essential nucleoside reverse
transcriptase inhibitor utilized in HAART for HIV-infected mothers to prevent
maternal-to-child transmission of HIV. Objective: This study aimed to identify
prenatal zidovudine-induced histopathological changes in the hippocampus and the
associated cognitive alterations in Swiss albino mice. Methods: Pregnant Swiss
albino mice were divided into two groups: Control and Treated, with six mice per
group. The treated group was orally administered ZDV at a dose of 50 mg/kg bwt
from gestation day 6th to 15th. Three pregnant mice from each group were allowed to
deliver and pups at 8 weeks were subjected to Morris Water Maze test to analyze the
cognitive changes. The remaining three pregnant mice from both the control and
treated groups were sacrificed on the 18th day of gestation and fetuses were
subjected for hippocampal histopathology using H&E staining. Results: The Morris
water maze test revealed impairment of spatial learning and memory in the prenatal
treated group. Microscopic examination of the hippocampus revealed degeneration
and reduction of the migrating neuroblast cells. A substantial reduction in the density
of neuroblast cells by enhanced apoptosis leads to empty spaces giving a spongy
appearence in the hippocampus. Conclusion: The findings of this research
demonstrate that prenatal ZDV exposure induces profound alterations in
hippocampal structure, resulting in spatial learning and memory defects.
Consequently, ZDV administration during pregnancy should be approached with
caution.