Transcriptomic analysis reveals new hippocampal gene networks induced by prolactin

Prolactin (Prl) is a pleiotropic hormone with multiple functions in several tissues and organs, including the brain. In the hippocampus, Prl has been implicated in several functions, including neuroprotection against excitotoxicity in lactating rats and in Prl-treated ovariectomized animals. However, the molecular mechanisms involved in Prl actions in the hippocampus have not been completely elucidated. The aim of this study was to analyse the hippocampal transcriptome of female Prl-treated ovariectomized rats. Transcriptomic analysis by RNASeq revealed 162 differentially expressed genes throughout 24 h of Prl treatment. Gene Ontology analysis of those genes showed that 37.65% were involved in brain processes that are regulated by the hippocampus, such as learning, memory and behaviour, as well as new processes that we did not foresee, such as glial differentiation, axogenesis, synaptic transmission, postsynaptic potential, and neuronal and glial migration. Immunodetection analysis demonstrated that Prl significantly modified microglial morphology, reduced the expression of Cd11b/c protein, and altered the content and location of the neuronal proteins Tau, Map2 and Syp, which are involved in axogenic and synaptic functions. This novel delineation of Prl activity in the hippocampus highlights its importance as a neuroactive hormone, opens a new avenue for understanding its actions and supports its participation in neuronal plasticity of this brain area. Overall design: We performed time course experiments during a period of 24 h of PRL treatment in adult ovariectomized rats (Rattus norvegicus) to obtain total hippocampus. The experimental groups were divided into Control (Solution salina 0.9%), and PRL (500µg/kg) treated during 3, 6 and 24 hours. Total RNA isolated from the hippocampus of each animal was sequenced by using the Hi-seq500 Illumina Platform in three biological replicates of each experimental group. A total of 365,050,464 reads, with an average of 30.4 million reads (paired end 2x72 bp long), were obtained for each of the four of the treated groups. Up to 93.5% of the reads were successfully mapped to transcripts in the NCBI, Rnor 6.0 as genome reference