Environmental Enrichment Protects Against Sepsis-Associated Encephalopathy-Induced Learning and Memory Deficits by Enhancing the Synthesis and Release of Vasopressin in the Supraoptic Nucleus

Abstract

Background: As a severe complication of sepsis, sepsis-associated encephalopathy (SAE) usually manifests as impaired learning and memory ability in survivors. Previous studies have reported that environmental enrichment (EE) can increase the learning and memory ability in different brain injury models. However, there has been no research on the possible positive effect of EE on SAE. Aim: The present study aimed to test the effect of EE on SAE-induced impairment of learning and memory and its related mechanisms. Methods: A Morris water maze test (MWM) was used to evaluate the learning and memory ability of SAE rats that received EE housing or not. The expression of vasopressin (VP) was assessed using immunofluorescence microscopy and enzyme-linked immunosorbent assays (ELISAs). The synthesis of VP in the supraoptic nucleus (SON) was determined using quantitative real-time reverse transcription-PCR analysis. Moreover, inflammatory markers and brain-derived neurotrophic factor (BDNF) were detected using ELISA. Results: The results showed that SAE induced a decreased learning and memory ability, while EE reversed this impairment. EE also enhanced the synthesis and secretion of VP in the SON. Blocking the action of VP in the hippocampus interrupted the EE-induced amelioration of learning and memory impairment. Moreover, EE induced changes to the levels of BDNF and cytokines in the hippocampus and these effects were mediated by VP binding to the VP receptor 1a. Conclusion: Our findings demonstrated that the enhanced synthesis and secretion of VP in the SON are a key determinant responsible for EE-induced alleviation of learning and memory deficits caused by SAE.