Transcriptomic analysis reveals new hippocampal gene networks induced by prolactin

Erika Alejandra Cabrera-Reyes,Mauricio Rodríguez-Dorantes,Edgar Ricardo Vázquez-Martínez,América Vanoye–Carlo,Nadia Alejandra Rivero-Segura,Marco Cerbón,Omar Collazo-Navarrete

doi:10.1038/s41598-019-50228-7

Abstract

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.

Highlights

Prolactin is a pleiotropic hormone in vertebrates with more than 300 described functions that fall into five major categories: reproduction, brain processes and behaviour, growth and development, water and electrolyte balance, and immunomodulation[1]
The results of the current study indicate that Prl administration induces transcriptional activity in the hippocampi of OVX female rats
The greatest number of differentially expressed genes was observed after 3 h of Prl treatment, and the differentially expressed genes were related to restructuring, remodelling, proliferation and neuronal development processes, indicating neuronal plasticity

Summary

Introduction

Prolactin is a pleiotropic hormone in vertebrates with more than 300 described functions that fall into five major categories: reproduction, brain processes and behaviour, growth and development, water and electrolyte balance, and immunomodulation[1]. Physiological behaviours regulated by the hippocampus are complex and implicated in several brain processes, including storage and consolidation of spatial and declarative memory and acquisition and retrieval of information[4]. In this regard, Prl improves memory, cognition and learning[5,6,7,8]. It has been demonstrated that prolactin treatment induces changes in the expression of the prolactin receptor and reduces the excitotoxicity generated by glutamate in primary hippocampal neuronal cultures[20]. Given that Prl regulates several brain processes, especially those that depend on the hippocampus, the present study aimed to elucidate the transcriptional effects of Prl in the hippocampus by means of transcriptomic analysis

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Conclusion