A Long-Term Enriched Environment Ameliorates the Accelerated Age-Related Memory Impairment Induced by Gestational Administration of Lipopolysaccharide: Role of Plastic Mitochondrial Quality Control

Abstract

Studies have shown that gestational inflammation accelerates age-related memory impairment in mother mice. An enriched environment (EE) can improve age-related memory impairment, whereas mitochondrial dysfunction has been implicated in the pathogenesis of brain aging. However, it is unclear whether an EE can counteract the accelerated age-related memory impairment induced by gestational inflammation and whether this process is associated with the disruption of mitochondrial quality control (MQC) processes. In this study, CD-1 mice received daily intraperitoneal injections of lipopolysaccharide (LPS, 50 μg/kg) or normal saline (CON group) during gestational days 15–17 and were separated from their offspring at the end of normal lactation. The mothers that received LPS were divided into LPS group and LPS plus EE (LPS-E) treatment groups based on whether the mice were exposed to an EE until the end of the experiment. At 6 and 18 months of age, the Morris water maze test was used to evaluate spatial learning and memory abilities. Quantitative reverse transcription polymerase chain reaction and Western blot were used to measure the messenber RNA (mRNA) and protein levels of MQC-related genes in the hippocampus, respectively. The results showed that all the aged (18 months old) mice underwent a striking decline in spatial learning and memory performances and decreased mRNA/protein levels related to mitochondrial dynamics (Mfn1/Mfn2, OPA1, and Drp1), biogenesis (PGC-1α), and mitophagy (PINK1/parkin) in the hippocampi compared with the young (6 months old) mice. LPS treatment exacerbated the decline in age-related spatial learning and memory and enhanced the reduction in the mRNA and protein levels of MQC-related genes but increased the levels of PGC-1α in young mice. Exposure to an EE could alleviate the accelerated decline in age-related spatial learning and memory abilities and the accelerated changes in MQC-related mRNA or protein levels resulting from LPS treatment, especially in aged mice. In conclusion, long-term exposure to an EE can counteract the accelerated age-related spatial cognition impairment modulated by MQC in CD-1 mother mice that experience inflammation during pregnancy.

Environmental Enrichment Protects Against Cognition Deficits Caused by Sepsis-Associated Encephalopathy

“…This is likely caused by effects of EE on neuroplastic responses to injury. The finding that an EE can reduce the cognition impairment of SAE is in accord with similar observations in animals with other forms of brain dysfunction [43][44][45][46][47][48]. Healthy environments also afford similar benefits to humans.…”

Environmental Enrichment Reverses Maternal Sleep Deprivation-Induced Anxiety-Like Behavior and Cognitive Impairment in CD-1 Mice

“…Several findings have indicated that EE improves activity-dependent synaptic plasticity, LTP, social interaction, and spatial learning and memory in models of Alzheimer’s disease, brain injury, Parkinson’s disease, and schizophrenia (Murueta-Goyena et al, 2019 ). Our lab has also shown that long-term EE attenuates the exacerbated age-related cognitive impairment induced by lipopolysaccharide exposure during pregnancy (Zhuang et al, 2021 ).…”

“…The Western blotting procedure was performed as previously described (Zhuang et al, 2021 ). Hippocampal tissue was lysed in RIRA lysis buffer, and protein concentrations were determined using a BCA Protein Assay Kit.…”

Environmental enrichment improves declined cognition induced by prenatal inflammatory exposure in aged CD-1 mice: Role of NGPF2 and PSD-95

“…However, escape latency can be affected by the swimming speed of mice. Because the swimming distance can better reflect the learning ability of aged mice in the learning phase ( Zhang et al, 2020 ), the swimming distance was preferentially used as an indicator of learning performance of mice in the present study, and the percentage of swimming distance and time in the target quadrant was recorded to evaluate the level of memory consolidation, as per previous studies ( Wu et al, 2020 ; Zhuang et al, 2021 ).…”