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

Abstract

IntroductionResearch suggests that prenatal inflammatory exposure could accelerate age-related cognitive decline that may be resulted from neuroinflammation and synaptic dysfunction during aging. Environmental enrichment (EE) may mitigate the cognitive and synaptic deficits. Neurite growth-promoting factor 2 (NGPF2) and postsynaptic density protein 95 (PSD-95) play critical roles in neuroinflammation and synaptic function, respectively.MethodsWe examined whether this adversity and EE exposure can cause alterations in Ngpf2 and Psd-95 expression. In this study, CD-1 mice received intraperitoneal injection of lipopolysaccharide (50 μg/kg) or normal saline from gestational days 15–17. After weaning, half of the male offspring under each treatment were exposed to EE. The Morris water maze was used to assess spatial learning and memory at 3 and 15 months of age, whereas quantitative real-time polymerase chain reaction and Western blotting were used to measure hippocampal mRNA and protein levels of NGPF2 and PSD-95, respectively. Meanwhile, serum levels of IL-6, IL-1β, and TNF-α were determined by enzyme-linked immunosorbent assay.ResultsThe results showed that aged mice exhibited poor spatial learning and memory ability, elevated NGPF2 mRNA and protein levels, and decreased PSD-95 mRNA and protein levels relative to their young counterparts during natural aging. Embryonic inflammatory exposure accelerated age-related changes in spatial cognition, and in Ngpf2 and Psd-95 expression. Additionally, the levels of Ngpf2 and Psd-95 products were significantly positively and negatively correlated with cognitive dysfunction, respectively, particularly in prenatal inflammation-exposed aged mice. Changes in serum levels of IL-6, IL-1β, and TNF-α reflective of systemic inflammation and their correlation with cognitive decline during accelerated aging were similar to those of hippocampal NGPF2. EE exposure could partially restore the accelerated decline in age-related cognitive function and in Psd-95 expression, especially in aged mice.DiscussionOverall, the aggravated cognitive disabilities in aged mice may be related to the alterations in Ngpf2 and Psd-95 expression and in systemic state of inflammation due to prenatal inflammatory exposure, and long-term EE exposure may ameliorate this cognitive impairment by upregulating Psd-95 expression.

Long-term environmental enrichment overcomes depression, learning, and memory impairment in elderly CD-1 mice with maternal sleep deprivation exposure

“…The present study demonstrated that long-term EE exposure improved MSD-induced depression and cognitive impairment in elderly mice. This result is consistent with the findings of our previous studies that EE alleviated the age-related cognitive impairment induced by prenatal inflammatory exposure ( Ni et al, 2022 ; Zhang Z. Z. et al, 2022 ).…”

“…The present study demonstrated that long-term EE exposure improved MSD-induced depression and cognitive impairment in elderly mice. This result is consistent with the findings of our previous studies that EE alleviated the age-related cognitive impairment induced by prenatal inflammatory exposure (Ni et al, 2022;. Collectively, these findings suggest that MSD results in behavioral difficulties in offspring that can persist into old age, which could be reversed by long-term EE.…”

“…Previous studies suggested that the expression levels of BDNF and inflammatory cytokines in the peripheral blood are related to the degree of depression and cognitive impairment of patients (Gelle et al, 2021;He et al, 2021). Our recent studies showed that upregulated expression of proinflammatory cytokines and downregulated expression of synaptic proteins are associated with age-related cognitive impairment (Ni et al, 2022;. Similarly, we found significant correlations between the expression levels of proinflammatory cytokines or synaptic plasticity-associated proteins and indicators of the tail suspension test, forced swimming test, and MWM test.…”

“…Previous studies suggested that the expression levels of BDNF and inflammatory cytokines in the peripheral blood are related to the degree of depression and cognitive impairment of patients ( Gelle et al, 2021 ; He et al, 2021 ). Our recent studies showed that upregulated expression of proinflammatory cytokines and downregulated expression of synaptic proteins are associated with age-related cognitive impairment ( Ni et al, 2022 ; Zhang Z. Z. et al, 2022 ).…”

Melatonin improves maternal sleep deprivation‐induced learning and memory impairment, inflammation, and synaptic dysfunction in murine male adult offspring

“…It is reported that chronic restraint stress from GD 12 to 18 increases anxiety‐ and depression‐like behaviors in rat offspring (Lei et al., 2020). Our previous studies document that prenatal inflammation exposure significantly aggravates aging‐related learning and memory dysfunction (Ni et al., 2022; Zhuang et al., 2021). In the present study, the MSD‐induced mice displayed increased escape latency and distance during the learning phase and a decreased time and distance percent in the target quadrant during the memory phase, suggesting cognitive impairment induced by MSD.…”