Evaluation of the dentate gyrus in adult mice exposed to acetaminophen (paracetamol) on postnatal day 10

Abstract

Acetaminophen (AAP; or paracetamol) is a widely used nonprescription drug with antipyretic and analgesic properties. Alarmingly, there is an increasing body of evidence showing that developmental exposure to AAP is associated with adverse behavioural outcomes later in life. We have previously shown that relevant doses of AAP in 10‐day‐old mice affected memory, learning and locomotor activity in the adult animals. Interestingly, the neurons of the dentate gyrus (DG) have a relatively late time of origin as they are generated during the first two weeks of postnatal life in rodents. Since the generation of these cells, which are important for memory processing, coincides with our AAP exposure, we aim to investigate if the cytoarchitecture of the DG is affected by postnatal day 10 AAP treatment. In addition, we investigate if markers for differentiation and migration in the hippocampus were affected by the same treatment. We did not observe any visual effects in adult DG cytoarchitecture, nor any changes of markers for differentiation/migration in the hippocampus in 24 hr after exposure. Even though a large effect size was estimated on adult DG thickness following AAP exposure, the estimated 95% CIs around the differences of the means reveal no significant effect. Hence, larger sample sizes are warranted to clarify if neonatal AAP exposure affects adult DG thickness in mice.

Implication of Hippocampal Neurogenesis in Autism Spectrum Disorder: Pathogenesis and Therapeutic Implications

“…It is well documented that the first 2 weeks after birth in mice, equivalent to the period from the last trimester of pregnancy to the first few years after birth in humans, is the critical period for DG development [ 164 ]. It has been indicated that early postnatal treatment potentially repairs the structure, which is associated with continuous symptom alleviation [ 165 ].…”

Inhibition of Adult Neurogenesis in Male Mice after Repeated Exposure to Paracetamol Overdose

“…A large body of evidence suggests the role of APAP overdose in neurodevelopmental impairment [15][16][17]. Nevertheless, few studies relate adult neurogenesis to paracetamol overdose toxicity.…”