Long-Term Environmental Enrichment Relieves Dysfunctional Cognition and Synaptic Protein Levels Induced by Prenatal Inflammation in Older CD-1 Mice

A mounting body of evidence suggests that prenatal inflammation may enhance the rate of age-associated cognitive decline and may involve aberrant amounts of synaptic proteins in the hippocampus, including synaptotagmin-1 (Syt1) and activity-regulated cytoskeleton-associated protein (Arc). However, l...

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Main Authors: Zhe-Zhe Zhang, Li-Ping Zeng, Jing Chen, Yong-Fang Wu, Ya-Tao Wang, Lan Xia, Qi-Gang Yang, Fang Wang, Gui-Hai Chen
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2022/1483101
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author Zhe-Zhe Zhang
Li-Ping Zeng
Jing Chen
Yong-Fang Wu
Ya-Tao Wang
Lan Xia
Qi-Gang Yang
Fang Wang
Gui-Hai Chen
author_facet Zhe-Zhe Zhang
Li-Ping Zeng
Jing Chen
Yong-Fang Wu
Ya-Tao Wang
Lan Xia
Qi-Gang Yang
Fang Wang
Gui-Hai Chen
author_sort Zhe-Zhe Zhang
collection DOAJ
description A mounting body of evidence suggests that prenatal inflammation may enhance the rate of age-associated cognitive decline and may involve aberrant amounts of synaptic proteins in the hippocampus, including synaptotagmin-1 (Syt1) and activity-regulated cytoskeleton-associated protein (Arc). However, little is known about the specific impact of adolescent environmental enrichment (EE) on age-associated cognitive decline and the changes in synaptic proteins caused by prenatal inflammation. In this study, CD-1 mice in late pregnancy were given intraperitoneal doses of lipopolysaccharide (LPS, 50 μg/kg) or normal saline. Offspring arising from LPS dams were divided into a LPS group and a LPS plus EE (LPS-E) group. The LPS-E mice were exposed to EE from 2 months of age until the end of the experiment (3 or 15 months old). The Morris water maze (MWM) was used to assess the spatial learning and memory capacities of experimental mice, while western blotting and RNA-scope were used to determine the expression levels of Arc and Syt1 in the hippocampus at the protein and mRNA levels, respectively. Analysis revealed that at 15 months of age, the control mice experienced a reduction in cognitive ability and elevated expression levels of Arc and Syt1 genes when compared to control mice at 3 months of age. The LPS-E group exhibited better cognition and lower protein and mRNA levels of Arc and Syt1 than mice in the LPS group of the same age. However, the enriched environment mitigated but did not counteract, the effects of prenatal inflammation on cognitive and synaptic proteins when tested at either 3 or 15 months of age. Our findings revealed that long-term environmental enrichment improved the expression levels of synaptic proteins in CD-1 mice and that this effect was linked to the dysfunctional cognition caused by prenatal inflammation; this process may also be involved in the reduction of hippocampal Arc and Syt1 gene expression.
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spelling doaj-art-bf3940d0ab094cf98e0cf4c1544ac0ce2025-02-03T01:22:27ZengWileyNeural Plasticity1687-54432022-01-01202210.1155/2022/1483101Long-Term Environmental Enrichment Relieves Dysfunctional Cognition and Synaptic Protein Levels Induced by Prenatal Inflammation in Older CD-1 MiceZhe-Zhe Zhang0Li-Ping Zeng1Jing Chen2Yong-Fang Wu3Ya-Tao Wang4Lan Xia5Qi-Gang Yang6Fang Wang7Gui-Hai Chen8Department of Neurology (Sleep Disorders)Department of Neurology (Sleep Disorders)Department of Neurology (Sleep Disorders)Department of Neurology (Sleep Disorders)Department of Neurology (Sleep Disorders)Department of NeurologyDepartment of Neurology or Department of Critical CareDepartment of Neurology or Department of Critical CareDepartment of Neurology (Sleep Disorders)A mounting body of evidence suggests that prenatal inflammation may enhance the rate of age-associated cognitive decline and may involve aberrant amounts of synaptic proteins in the hippocampus, including synaptotagmin-1 (Syt1) and activity-regulated cytoskeleton-associated protein (Arc). However, little is known about the specific impact of adolescent environmental enrichment (EE) on age-associated cognitive decline and the changes in synaptic proteins caused by prenatal inflammation. In this study, CD-1 mice in late pregnancy were given intraperitoneal doses of lipopolysaccharide (LPS, 50 μg/kg) or normal saline. Offspring arising from LPS dams were divided into a LPS group and a LPS plus EE (LPS-E) group. The LPS-E mice were exposed to EE from 2 months of age until the end of the experiment (3 or 15 months old). The Morris water maze (MWM) was used to assess the spatial learning and memory capacities of experimental mice, while western blotting and RNA-scope were used to determine the expression levels of Arc and Syt1 in the hippocampus at the protein and mRNA levels, respectively. Analysis revealed that at 15 months of age, the control mice experienced a reduction in cognitive ability and elevated expression levels of Arc and Syt1 genes when compared to control mice at 3 months of age. The LPS-E group exhibited better cognition and lower protein and mRNA levels of Arc and Syt1 than mice in the LPS group of the same age. However, the enriched environment mitigated but did not counteract, the effects of prenatal inflammation on cognitive and synaptic proteins when tested at either 3 or 15 months of age. Our findings revealed that long-term environmental enrichment improved the expression levels of synaptic proteins in CD-1 mice and that this effect was linked to the dysfunctional cognition caused by prenatal inflammation; this process may also be involved in the reduction of hippocampal Arc and Syt1 gene expression.http://dx.doi.org/10.1155/2022/1483101
spellingShingle Zhe-Zhe Zhang
Li-Ping Zeng
Jing Chen
Yong-Fang Wu
Ya-Tao Wang
Lan Xia
Qi-Gang Yang
Fang Wang
Gui-Hai Chen
Long-Term Environmental Enrichment Relieves Dysfunctional Cognition and Synaptic Protein Levels Induced by Prenatal Inflammation in Older CD-1 Mice
Neural Plasticity
title Long-Term Environmental Enrichment Relieves Dysfunctional Cognition and Synaptic Protein Levels Induced by Prenatal Inflammation in Older CD-1 Mice
title_full Long-Term Environmental Enrichment Relieves Dysfunctional Cognition and Synaptic Protein Levels Induced by Prenatal Inflammation in Older CD-1 Mice
title_fullStr Long-Term Environmental Enrichment Relieves Dysfunctional Cognition and Synaptic Protein Levels Induced by Prenatal Inflammation in Older CD-1 Mice
title_full_unstemmed Long-Term Environmental Enrichment Relieves Dysfunctional Cognition and Synaptic Protein Levels Induced by Prenatal Inflammation in Older CD-1 Mice
title_short Long-Term Environmental Enrichment Relieves Dysfunctional Cognition and Synaptic Protein Levels Induced by Prenatal Inflammation in Older CD-1 Mice
title_sort long term environmental enrichment relieves dysfunctional cognition and synaptic protein levels induced by prenatal inflammation in older cd 1 mice
url http://dx.doi.org/10.1155/2022/1483101
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