Neurobehavioral, neurochemical and synaptic plasticity perturbations during postnatal life of rats exposed to chloroquine in-utero

Neurobehavioral, neurochemical and synaptic plasticity perturbations during postnatal life of rats exposed to chloroquine in-utero

Author by Olayemi Joseph Olajide

Journal/Publisher: Sciencedirect (elsevier)

Volume/Edition: 86

Language: English

Pages: 1 - 14

Abstract

Despite reports that quinoline antimalarials including chloroquine (Chq) exhibit idiosyncratic neuropsychiatric
effects even at low doses, the drug continues to be in widespread use during pregnancy. Surprisingly, very few
studies have examined the potential neurotoxic action of Chq exposure at different points of gestation or how this
phenomenon may affect neurophysiological well-being in later life. We therefore studied behavior, and the
expression of specific genes and neurochemicals modulating crucial neural processes in offspring of rats exposed
to prophylactic dose of Chq during different stages of gestation. Pregnant rats were injected 5 mg/kg/day (3
times) of Chq either during early- (first week), mid- (second week), late- (third week), or throughout- (all weeks)
gestation, while controls received PBS injection. Behavioral characterization of offspring between postnatal days
15–20 in the open field, Y-maze, elevated plus and elevated zero mazes revealed that Chq evoked anxiogenic
responses and perturbed spatial memory in rats, although locomotor activity was generally unaltered. In the
prefrontal cortex (PFC), hippocampus and cerebellum of rats prenatally exposed to Chq, RT-qPCR analysis
revealed decreased mRNA expression of presynaptic marker synaptophysin, which was accompanied by downregulation
of postsynaptic marker PSD95. Synaptic marker PICK1 expression was also downregulated in the
hippocampus but was unperturbed in the PFC and cerebellum. In addition to recorded SOD downregulation in
cortical and hippocampal lysates, induction of oxidative stress in rats prenatally exposed to Chq was corroborated
by lipid peroxidation as evinced by increased MDA levels. Offspring of rats infused with Chq at midgestation
and weekly treatment throughout gestation were particularly susceptible to neurotoxic changes,
especially in the hippocampus. Interestingly, Chq did not cause histopathological changes in any of the brain
areas. Taken together, our findings causally link intrauterine exposure to Chq with postnatal behavioral
impairment and neurotoxic changes in rats.


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