Prolactin Reduces Hippocampal Parvalbumin and GABAA Receptor Expression in Female Mice

Abstract

Introduction: Parvalbumin (PV)-positive cells are strategic elements of neuronal networks capable of influencing memory and learning processes. However, it is not known whether pituitary hormones may be related to PV expression in the hippocampus - a part of the limbic system with important functions in learning and memory.

Objective: Since previous studies indicate that prolactin (PRL) plays a significant role in hippocampal-dependent learning and synaptic plasticity, we hypothesized that a rise in PRL levels can modify PV expression in the hippocampus.

Methods: We employed biochemical, immunohistochemistry, and densitometry techniques - as well as a behavioural assay - in a hyperprolactinemia model using subcutaneous osmotic pumps in female mice.

Results: PRL treatment via osmotic pump induced an increase in PRL receptor (PRLR) expression in most regions of the hippocampus analysed by Western blotting and immunohistochemistry methods. Fluorescent densitometry analysis revealed that PV expression decreases in the same layers in the hippocampus following PRL treatment, while double labelling immunostaining indicated close localization of PV and PRLR in PV-positive interneurons. In addition, we found that PRL induced a reduction in the β2/3 subunit of GABAA receptor (GABAAR) expression that was linearly correlated with the reduction in PV expression. This reduction in the β2/3 subunit of GABAAR expression was maintained in trained animals in which PRL treatment improved the learning of a spatial memory task.

Conclusions: These data show, for the first time, that an increase in PRL level is associated with changes in key constituent elements of inhibitory circuits in the hippocampus and may be of relevance for the alterations in cognitive function reported in hyperprolactinemia.

Keywords: Hyperprolactinemia; Inhibition; Parvalbumin-positive interneurons; β2/3 subunit of GABAA receptors.