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.催乳素（Prolactin，Prl）是一种多效性激素，可在包括大脑在内的诸多组织与器官中发挥多样生物学功能。在海马体中，催乳素已被证实参与多项生理过程，例如在泌乳大鼠以及经催乳素处理的去卵巢动物中，发挥抗兴奋性毒性的神经保护作用。然而，催乳素在海马体中发挥调控作用的分子机制尚未完全阐明。本研究旨在分析经催乳素处理的去卵巢雌性大鼠的海马转录组。通过RNASeq开展的转录组学分析显示，在催乳素处理后的24小时内，共鉴定得到162个差异表达基因。针对上述基因的基因本体（Gene Ontology，GO）分析结果表明，其中37.65%的基因参与海马体调控的大脑生理过程，如学习、记忆与行为调控；同时还涵盖了此前未被预见的全新生物学进程，包括胶质细胞分化、轴突发生、突触传递、突触后电位以及神经元与神经胶质细胞迁移。免疫检测分析证实，催乳素可显著改变小胶质细胞形态，下调Cd11b/c蛋白的表达水平，并调控参与轴突发生与突触功能的神经元蛋白Tau、Map2及Syp的含量与定位。本研究对催乳素在海马体中的活性进行了全新的阐释，凸显了其作为神经活性激素的重要生物学意义，为深入解析其作用机制开辟了新的研究方向，同时也为其参与该脑区神经元可塑性的结论提供了支持依据。