Exercise Reverses Behavioral and Synaptic Abnormalities after Maternal Inflammation

Andoh, Megumi; Shibata, Kazuki; Okamoto, Kazuki; Onodera, Junya; Morishita, Kohei; Miura, Yuki; Ikegaya, Yuji; Koyama, Ryuta

doi:10.1016/j.celrep.2019.05.015

Cited by 60 publications

(59 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, embryonic inflammation and adolescent stress are shown to inhibit dendritic growth, induce neuronal remodeling and impaired synaptic transmission and plasticity, and lead to cognitive impairment in the aged mice ( Lesuis et al, 2019 ; Tellez-Merlo et al, 2019 ; Wang et al, 2020 ). In contrast, an adolescent EE can partly reverse behavioral and synaptic abnormalities resulting from embryonic inflammation ( Andoh et al, 2019 ). Under normal circumstances, Staufen is implicated in the transport and regulation of dendritic mRNA, so downregulation of Staufen expression can lead to a significant reduction in the number of dendritic spines and miniature excitatory postsynaptic currents, which are generally assumed to contribute to impaired synaptic plasticity ( Goetze et al, 2006 ; Popper et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…resulting from embryonic inflammation (Andoh et al, 2019). Under normal circumstances, Staufen is implicated in the transport and regulation of dendritic mRNA, so downregulation of Staufen expression can lead to a significant reduction in the number of dendritic spines and miniature excitatory postsynaptic currents, which are generally assumed to contribute to impaired synaptic plasticity (Goetze et al, 2006;Popper et al, 2018).…”

Section: The Association Between Altered Staufen Expression and Cognimentioning

confidence: 99%

See 1 more Smart Citation

Effects of Embryonic Inflammation and Adolescent Psychosocial Environment on Cognition and Hippocampal Staufen in Middle-Aged Mice

Zhang

et al. 2020

Front. Aging Neurosci.

View full text Add to dashboard Cite

Accumulating evidence has indicated that embryonic inflammation could accelerate age-associated cognitive impairment, which can be attributed to dysregulation of synaptic plasticity-associated proteins, such as RNA-binding proteins (RBPs). Staufen is a double-stranded RBP that plays a critical role in the modulation of synaptic plasticity and memory. However, relatively few studies have investigated how embryonic inflammation affects cognition and neurobiology during aging, or how the adolescent psychosocial environment affects inflammation-induced remote cognitive impairment. Consequently, the aim of this study was to investigate whether these adverse factors can induce changes in Staufen expression, and whether these changes are correlated with cognitive impairment. In our study, CD-1 mice were administered lipopolysaccharides (LPS, 50 µg/kg) or an equal amount of saline (control) intraperitoneally during days 15-17 of gestation. At 2 months of age, male offspring were randomly exposed to stress (S), an enriched environment (E), or not treated (CON) and then assigned to five groups: LPS, LPS+S, LPS+E, CON, and CON+S. Mice were evaluated at 3-month-old (young) and 15-month-old (middle-aged). Cognitive function was assessed using the Morris water maze test, while Staufen expression was examined at both the protein and mRNA level using immunohistochemistry/western blotting and RNAscope technology, respectively. The results showed that the middle-aged mice had worse cognitive performance and higher Staufen expression than young mice. Embryonic inflammation induced cognitive impairment and increased Staufen expression in the middle-aged mice, whereas adolescent stress/an enriched environment would accelerated/mitigated these effects. Meanwhile, Staufen expression was closely correlated with cognitive performance. Our findings suggested embryonic inflammation can accelerate age-associated learning and memory impairments, and these effects may be related to the Staufen expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: The Association Between Altered Staufen Expression and Cognimentioning

confidence: 99%

Effects of Embryonic Inflammation and Adolescent Psychosocial Environment on Cognition and Hippocampal Staufen in Middle-Aged Mice

Zhang

et al. 2020

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…Seizure-like EEG signals have also been confirmed to occur in the cerebral cortex and hippocampus in AD model mice [7]. Furthermore, neuronal activity is increased in animal models of multiple sclerosis (MS), Parkinson's disease (PD) and autism spectrum disorders (ASDs), brain diseases that are sometimes accompanied by epileptic seizures [8][9][10][11][12]. Thus, it is likely that synaptic E/I imbalance is the main cause of epilepsy, but whether glial cells are involved has not yet been clarified.…”

Section: Introductionmentioning

confidence: 99%

Synaptic Pruning by Microglia in Epilepsy

Andoh

Ikegaya

Koyama

2019

JCM

Self Cite

View full text Add to dashboard Cite

Structural and functional collapse of the balance between excitatory (E) and inhibitory (I) synapses, i.e., synaptic E/I balance, underlies the pathogeneses of various central nervous system (CNS) disorders. In epilepsy, the synaptic E/I balance tips toward excitation; thus, most of the existing epileptic remedies have focused on how to directly suppress the activity of neurons. However, because as many as 30% of patients with epilepsy are drug resistant, the discovery of new therapeutic targets is strongly desired. Recently, the roles of glial cells in epilepsy have gained attention because glial cells manipulate synaptic structures and functions in addition to supporting neuronal survival and growth. Among glial cells, microglia, which are brain-resident immune cells, have been shown to mediate inflammation, neuronal death and aberrant neurogenesis after epileptic seizures. However, few studies have investigated the involvement of synaptic pruning—one of the most important roles of microglia—in the epileptic brain. In this review, we propose and discuss the hypothesis that synaptic pruning by microglia is enhanced in the epileptic brain, drawing upon the findings of previous studies. We further discuss the possibility that aberrant synaptic pruning by microglia induces synaptic E/I imbalance, promoting the development and aggravation of epilepsy.

show abstract

“…It has also been reported that neuronal activity modulates synaptic properties through microglial activation both in physiological and pathological conditions . Our neuronal culture includes few microglia, thus, it can be assumed that neuronal activity directly affects synapse density.…”

Section: Resultsmentioning

confidence: 99%

Induced neuronal activity does not attenuate amyloid beta‐induced synaptic loss in vitro

Kono

Kim

Nagata

et al. 2019

Neuropsychopharm Rep

Self Cite

View full text Add to dashboard Cite

Neuropsychopharmacology Reports. 2019;39:306-311. wileyonlinelibrary.com/journal/nppr | INTRODUC TI ONAlzheimer's disease (AD), which is the most common cause of dementia, is a progressive neurodegenerative disorder that significantly affects patients' cognitive function and their quality of life. In the brains of AD patients, accumulated amyloid beta (Aβ) is one of the major pathological characteristics of AD. 1 Aβ has been linked to cognitive dysfunction in AD patients 2 partly because Aβ induces abnormalities in synaptic function and structure, including the loss of synapses. 3,4 In the healthy brain, specifically during development, neuronal activity plays a key role in regulating the formation and elimination of synapses. 5 It has also been suggested that, in the AD brain, synapse density is influenced by neuronal activity. 6 However, confirmation of a direct link between neuronal activity and Aβ-induced synapse loss is lacking. Here, we directly investigated whether neuronal activity modulates Aβ-induced synapse loss using primary cultures of hippocampal neurons. | ME THODSHippocampal neuronal cultures were prepared from postnatal day 1 B57BL6/J mice (SLC, Shizuoka, Japan) as previously described. 7 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractAim: The accumulation of amyloid beta (Aβ) is one of the characteristics of Alzheimer's disease. The excessive accumulation of Aβ has been suggested to result in a decrease in the number of synapses. Although the number of synapses is generally modulated by neuronal activity, whether neuronal activity affects Aβ-induced synapse loss remains unknown. Therefore, we addressed this question using a primary culture of hippocampal neurons. Method:The neuronal activity of cultured hippocampal neurons from mouse pups was increased using the chemogenetic technique designer receptors exclusively activated by designer drugs (DREADD). The cultured neurons were treated with Aβ, and synapse density was assessed by immunocytochemistry.Results: Aβ decreased the synapse density probably by decreasing postsynapse. On the other hand, enhanced neuronal activity did not affect the synapse density significantly. However, there was a trend that enhanced neuronal activity increased especially presynapse density. Conclusion:We found that enhanced neuronal activity did not affect Aβ-induced synapse loss in vitro. K E Y W O R D SAlzheimer's disease, amyloid beta, hippocampus, neuronal activity, synapse | 307 KONO et al.

show abstract

Exercise Reverses Behavioral and Synaptic Abnormalities after Maternal Inflammation

Cited by 60 publications

References 51 publications

Effects of Embryonic Inflammation and Adolescent Psychosocial Environment on Cognition and Hippocampal Staufen in Middle-Aged Mice

Effects of Embryonic Inflammation and Adolescent Psychosocial Environment on Cognition and Hippocampal Staufen in Middle-Aged Mice

Synaptic Pruning by Microglia in Epilepsy

Induced neuronal activity does not attenuate amyloid beta‐induced synaptic loss in vitro

Contact Info

Product

Resources

About