The Plastic and Functional Changes in Hippocampal Neurons During Pregnancy, Delivery and Postpartum are Reversed by Offspring Deprivation

Abstract

Background: Pregnancy and lactation are governed by hormones and neurophysiological processes, including differential expression of trophic factors, functional and structural synaptic plasticity, and neurogenesis in different brain areas. Objectives: The aim of the study was to evaluate the number of neurotrophic factors, synaptic plasticity, and neurogenesis in the hippocampus of rats during pregnancy, lactation, as well as in dams that were deprived of their pups one week after birth or treated with Finasteride or Clomiphene. Methods: Adult female Sprague Dawley CD rats were treated with finasteride (25 mg/kg, subcutaneously) or clomiphene (5 mg/kg, intragastrically) from day 12 to 18 of pregnancy. Dams during pregnancy, lactation, and those deprived of their pups, which were sacrificed 7 days after delivery, were used to study Brain-Derived Neurotrophic Factor (BDNF) and Activity-regulated Cytoskeletal (Arc) protein expression, dendritic spine density (DSD), and cell proliferation in the hippocampus. Results: BDNF, Arc, and DSD markedly increased after 21 days of pregnancy (the time of delivery), an effect that lasted for 21 days during lactation and was abolished by physiological weaning (21 days after delivery). The modifications in the mentioned parameters were associated with a dramatic reduction of neurosteroid content when compared to estrus females. In contrast, after 21 days of pregnancy, an increase in cell proliferation and a decrease during the first three weeks of postpartum were observed. Finasteride and clomifene failed to modify the changes in BDNF and Arc content elicited by pregnancy and delivery. Pups deprivation induced a rapid reduction in the amount of BDNF, Arc, and DSD while increasing cell proliferation. Conclusion: In rats, the changes in plastic properties of hippocampal neurons during pregnancy, lactation, and pups deprivation may play a crucial role in the modulation of maternal care.