Sex-dependent changes of hippocampal synaptic plasticity and cognitive performance in C57BL/6J mice exposed to neonatal repeated maternal separation

Talani, Giuseppe; Biggio, Francesca; Gorule, Ashish Avinash; Licheri, Valentina; Saolini, Eleonora; Colombo, Daniele; Sarigu, Gabriele; Petrella, Michele; Vedele, Francescangelo; Biggio, Giovanni; Sanna, Enrico

doi:10.1016/j.neuropharm.2022.109301

Cited by 12 publications

(10 citation statements)

References 85 publications

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“…Previous studies have suggested that there are sex differences in the effects of early life stress on behavioral phenotype of offspring rodents. For example, one study showed that cognitive decline and synaptic dysfunction were observed in male offspring mice suffered from maternal separation, but not in female offspring mice ( Talani et al, 2023 ). Other study found that prenatal restraint stress significantly increased anxiety-like behavior in male offspring mice and attenuated it in female offspring mice ( Zuena et al, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Wei

et al. 2023

Front. Aging Neurosci.

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Early-life stress disrupts central nervous system development and increases the risk of neuropsychiatric disorder in offspring based on rodent studies. Maternal sleep deprivation (MSD) in rodents has also been associated with depression and cognitive decline in adult offspring. However, it is not known whether these issues persist into old age. Environmental enrichment is a non-pharmacological intervention with proven benefits in improving depression and cognitive impairment; however, it is unclear whether these benefits hold for aging mice following MSD exposure. The aim of this study was to explore the effects of MSD on depression and cognition in elderly offspring CD-1 mice and to determine whether long-term environmental enrichment could alleviate these effects by improving neuroinflammation and synaptic plasticity. The offspring mice subjected to MSD were randomly assigned to either a standard environment or an enriched environment. At 18 months of age, the forced swimming and tail suspension tests were used to evaluated depression-like behaviors, and the Morris water maze test was used to evaluate cognitive function. The expression levels of hippocampal proinflammatory cytokines and synaptic plasticity-associated proteins were also measured. MSD increased depression-like behaviors and impaired cognition function in aging CD-1 offspring mice. These effects were accompanied by upregulated interleukin (IL)-1β, IL-6, and tumor necrosis factor-α expression, and downregulated brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density-95, and synaptophysin expression in the hippocampus. All of these changes were reversed by long-term exposure to an enriched environment. These findings suggest that MSD exerts long-term effects on the behaviors of offspring in mice, leading to depression and cognitive impairment in older age. Importantly, long-term environmental enrichment could counteract the behavior difficulties induced by MSD through improving hippocampal proinflammatory cytokines and synaptic plasticity-associated proteins.

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Section: Discussionmentioning

confidence: 99%

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

Zhang

Wei

et al. 2023

Front. Aging Neurosci.

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“…Early adverse life experience during neurodevelopmental periods is a well-recognized risk factor for several psychiatric disorders. , One consistent consequence of ELS is cognitive deficits. − Previous studies have found that mice subjected to ELS exhibit substantial cognitive impairment in hippocampus-dependent learning and memory tasks, such as the spatial object recognition test, compared to the controls. − Therefore, the ELS animal model has been valuable for investigating treatments targeting cognitive deficits in psychiatric disorders. In this study, we examined the cognitive impairment in MS mice through behavioral tests.…”

Section: Discussionmentioning

confidence: 99%

Activation of GPR55 Ameliorates Maternal Separation-Induced Learning and Memory Deficits by Augmenting 5-HT Synthesis in the Dorsal Raphe Nucleus of Juvenile Mice

Sun,

Du,

Zhang

et al. 2024

ACS Omega

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Maternal separation (MS) represents a profound early life stressor with enduring impacts on neuronal development and adult cognitive function in both humans and rodents. MS is associated with persistent dysregulations in neurotransmitter systems, including the serotonin (5-HT) pathway, which is pivotal for mood stabilization and stress-coping mechanisms. Although the novel cannabinoid receptor, GPR55, is recognized for its influence on learning and memory, its implications on the function and synaptic dynamics of 5-HT neurons within the dorsal raphe nucleus (DRN) remain to be elucidated. In this study, we sought to discern the repercussions of GPR55 activation on 5-HT synthesis within the DRN of adult C57BL/6J mice that experienced MS. Concurrently, we analyzed potential alterations in excitatory synaptic transmission, long-term synaptic plasticity, and relevant learning and memory outcomes. Our behavioral assessments indicated a marked amelioration in MS-induced learning and memory deficits following GPR55 activation. In conjunction with this, we noted a substantial decrease in 5-HT levels in the MS model, while GPR55 activation stimulated tryptophan hydroxylase 2 synthesis and fostered the release of 5-HT. Electrophysiological patch-clamp analyses highlighted the ability of GPR55 activation to alleviate MS-induced cognitive deficits by modulating the frequency and magnitude of miniature excitatory postsynaptic currents within the DRN. Notably, this cognitive enhancement was underpinned by the phosphorylation of both NMDA and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. In summary, our findings underscore the capacity of GPR55 to elevate 5-HT synthesis and modify synaptic transmissions within the DRN of juvenile mice, positing GPR55 as a promising therapeutic avenue for ameliorating MS-induced cognitive impairment.

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“…Several studies have reported that early‐life stress has a sex‐dependent effect on offspring mice. For example, repeated maternal separation impaired synaptic plasticity and cognitive function in male offspring mice, but not in female offspring mice (Talani et al., 2023). Prenatal restraint stress increased anxiety‐like behavior in offspring male rats and ameliorated anxiety‐like behavior and cognitive impairment in female rats (Zuena et al., 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have reported that early-life stress has a sexdependent effect on offspring mice. For example, repeated maternal separation impaired synaptic plasticity and cognitive function in male offspring mice, but not in female offspring mice (Talani et al, 2023).…”

Section: An Enriched Environment Reversed Changes In Synaptic Plastic...mentioning

confidence: 96%

An enriched environment improves maternal sleep deprivation‐induced cognitive deficits and synaptic plasticity via hippocampal histone acetylation

Zhang

Wei

et al. 2023

Brain and Behavior

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Introduction Growing evidence clearly demonstrates that maternal rodents exposure to sleep deprivation (SD) during late pregnancy impairs learning and memory in their offspring. Epigenetic mechanisms, particularly histone acetylation, are known to be involved in synaptic plasticity, learning, and memory. We hypothesize that the cognitive decline induced by SD during late pregnancy is associated with histone acetylation dysfunction, and this effect could be reversed by an enriched environment (EE). Methods In the present study, pregnant CD‐1 mice were exposed to SD during the third trimester of pregnancy. After weaning, all offspring were randomly assigned to two subgroups in either a standard environment or an EE. When offspring were 3 months old, the Morris water maze was used to evaluate hippocampal‐dependent learning and memory ability. Molecular biological techniques, including western blot and real‐time fluorescence quantitative polymerase chain reaction, were used to examine the histone acetylation pathway and synaptic plasticity markers in the hippocampus of offspring. Results The results showed that the following were all reversed by EE treatment: maternal SD (MSD)‐induced cognitive deficits including spatial learning and memory; histone acetylation dysfunction including increased histone deacetylase 2 (HDAC2) and decreased histone acetyltransferase (CBP), and the acetylation levels of H3K9 and H4K12; synaptic plasticity dysfunction including decreased brain‐derived neurotrophic factor; and postsynaptic density protein‐95. Conclusions Our findings suggested that MSD could damage learning ability and memory in offspring via the histone acetylation pathway. This effect could be reversed by EE treatment.

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Sex-dependent changes of hippocampal synaptic plasticity and cognitive performance in C57BL/6J mice exposed to neonatal repeated maternal separation

Cited by 12 publications

References 85 publications

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

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

Activation of GPR55 Ameliorates Maternal Separation-Induced Learning and Memory Deficits by Augmenting 5-HT Synthesis in the Dorsal Raphe Nucleus of Juvenile Mice

An enriched environment improves maternal sleep deprivation‐induced cognitive deficits and synaptic plasticity via hippocampal histone acetylation

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