Neuroinflammaging underlies emotional disturbances and circadian rhythm disruption in young male senescence-accelerated mouse prone 8 mice

Ito, Naoki; Takemoto, Hiroaki; Hasegawa, Ayana; Sugiyama, Chika; Honma, K.; Nagai, Takayuki; Kobayashi, Yoshinori; Odaguchi, Hiroshi

doi:10.1016/j.exger.2020.111109

Cited by 9 publications

(11 citation statements)

References 72 publications

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“…Once activated, microglia undergo morphological changes, and produce pro-inflammatory cytokines, including IL-1β ( Tanaka et al, 2006 ; Imamura et al, 2011 ). Ito et al recently demonstrated that microglia in 17-week-old SAMP8 under physiological condition were primed and that neuroinflammatory response to lipopolysaccharide was significantly greater in SAMP8 than in SAMR1 ( Ito et al, 2020 ). Therefore, it is reasonable that microglia were activated in the SAMP8 + CLP group in our study.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1β Modulates Synaptic Transmission and Synaptic Plasticity During the Acute Phase of Sepsis in the Senescence-Accelerated Mouse Hippocampus

Hoshino

Uchinami

Uchida

et al. 2021

Front. Aging Neurosci.

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BackgroundAging and pre-existing cognitive impairment are considered to be independent risk factors for sepsis-associated encephalopathy. This study aimed to investigate the manner in which aging and pre-existing cognitive dysfunction modified neuroinflammation, synaptic plasticity, and basal synaptic transmission during the acute phase of sepsis using Senescence-Accelerated Mice Prone 8 (SAMP8) and Senescence-Accelerated Resistant Mice 1 (SAMR1).MethodsWe used 6-month-old SAMP8 and SAMR1. Sepsis was induced using cecal ligation and puncture (CLP). The animal’s hippocampi and blood were collected for subsequent investigations 24 h after surgery.ResultsLong-term potentiation (LTP) was impaired in the Shaffer-collateral (SC)-CA1 pathway of the hippocampus in SAMP8 without surgery compared to the age-matched SAMR1, which was reflective of cognitive dysfunction in SAMP8. CLP impaired the SC-CA1 LTP in SAMR1 compared to the sham-operated controls, but not in SAMP8. Moreover, CLP decreased the input-output curve and increased the paired-pulse ratio in SAMP8, suggesting the reduced probability of basal synaptic transmission due to sepsis. Immunohistochemical analysis revealed that CLP elevated IL-1β levels, especially in the hippocampi of SAMP8 with microglial activation. In vivo peripheral IL-1 receptor antagonist (IL-1ra) administration in the septic SAMP8 revealed that the neuroinflammation was not correlated with the peripheral elevation of IL-1β. Ex vivo IL-1ra administration to the hippocampus ameliorated LTP impairment in SAMR1 and the reduction in basal transmission in SAMP8 after sepsis.ConclusionsThe mechanism of the modulation of synaptic transmission and synaptic plasticity by the acute stage of sepsis differed between SAMR1 and SAMP8. These changes were related to centrally derived IL-1 receptor-mediated signaling and were accompanied by microglial activation, especially in SAMP8.

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Section: Discussionmentioning

confidence: 99%

Interleukin-1β Modulates Synaptic Transmission and Synaptic Plasticity During the Acute Phase of Sepsis in the Senescence-Accelerated Mouse Hippocampus

Hoshino

Uchinami

Uchida

et al. 2021

Front. Aging Neurosci.

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“…Recent studies have also reported that neuroinflammation plays an important role in the pathology of emotional disorders, including depression [ 16 – 20 ]. This suggests a close link between neuroinflammaging and depression, as demonstrated by our recent finding that neuroinflammaging underlies emotional disturbances in a senescence-accelerated mouse model [ 21 ]. Several animal and human studies have reported that existing antidepressants attenuate neuroinflammation [ 22 – 25 ], but because antidepressants affect the metabolism of glucose [ 26 ], lipids [ 27 ], and other drugs [ 28 – 31 ] and may lead to exacerbation of diseases comorbid with depression, attention should be paid to long-term antidepressant treatment in older individuals with polypharmacy.…”

Section: Introductionmentioning

confidence: 64%

“…The decrease in Arg1 expression was significantly increased by treatment with Kampo formulas (Bonferroni’s post-hoc test, P < 0.01). The ratio of NLRP3 to Arg1, which represents the balance between pro- and anti-inflammatory phenotypes [ 21 ], was significantly increased in the water-administered SAMP8 mice as compared with the water-administered SAMR1 mice ( Figure 3D , left; Bonferroni’s post-hoc test, P < 0.05). This increase was significantly reduced in SAMP8 mice treated with Kampo formulas (Bonferroni’s post-hoc test, P < 0.01), suggesting that Kampo formulas abrogate hippocampal neuroinflammation in SAMP8 mice aged 19 weeks.…”

Section: Resultsmentioning

confidence: 99%

“…In the present study, LPS injection was used to evaluate neuroinflammatory priming with aging [ 21 , 78 – 80 ]. Several findings have been reported that expression of TLR4, which is a well-known innate immune receptor for LPS, is elevated with aging [ 81 , 82 ].…”

Section: Discussionmentioning

confidence: 99%

“…To evaluate this hypothesis, we examined whether KS and NKS exerted antidepressant-like effects and neuroinflammation-suppressive effects in senescence-accelerated mouse prone 8 (SAMP8) mice, which show depressive- and anxiety-like behaviors, circadian rhythm disruption, and neuroinflammation associated with aging [ 21 ]. Furthermore, we compared the effects of KS and NKS with those of another Kampo formula, hachimijiogan (HJG), which has traditionally been used to treat several aging-related disorders, including cognitive impairments [ 50 , 51 ] and irritable bladder [ 52 ].…”

Section: Introductionmentioning

confidence: 99%

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Kampo formulas alleviate aging-related emotional disturbances and neuroinflammation in male senescence-accelerated mouse prone 8 mice

Ito

Maruko

Oshima

et al. 2022

Aging

Self Cite

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Aging-induced neuroinflammation, also known as neuroinflammaging, plays a pivotal role in emotional disturbances, including depression and anxiety, in older individuals, thereby leading to cognitive dysfunction. Although numerous studies have focused on therapeutic strategies for cognitive impairment in older individuals, little research has been performed on treating its preceding emotional disturbances. Here, we examined whether Kampo formulas (kososan [KS], nobiletin-rich kososan [NKS], and hachimijiogan [HJG]) can ameliorate aging-induced emotional disturbances and neuroinflammation in mice. The depression-like behaviors observed in SAMP8 mice, relative to normally aging SAMR1 mice, were significantly prevented by treatment with Kampo formulas for 13 weeks. Western blot analysis revealed that hippocampal neuroinflammation was significantly abrogated by Kampo formulas. KS and NKS also significantly attenuated the hippocampal neuroinflammatory priming induced by lipopolysaccharide (LPS, 0.33 mg/kg, i.p. ) challenge in SAMP8 mice. Hippocampal IL-1β, IL-6, and MCP-1 levels were significantly decreased in NKS-treated SAMP8 mice. KS and NKS showed significantly reduced tau accumulation in the brains of SAMP8 mice. RNA-sequencing revealed that each Kampo formula led to unique dynamics of hippocampal gene expression and appeared to abrogate hippocampal inflammatory responses. HJG significantly blocked the LPS-induced increase in serum IL-6 and MCP-1. These results suggest that Kampo formulas would be useful for treating aging-induced depression, in part by regulating neuroinflammatory pathways. This finding may pave the way for the development of therapeutic strategies for aging-related emotional disturbances, which may contribute to the prevention of cognitive dysfunction in older individuals.

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Subsequent maternal sleep deprivation aggravates cognitive impairment by modulating hippocampal neuroinflammatory responses and synaptic function in maternal isoflurane‐exposed offspring mice

Zhang,

Wei,

Jing

et al. 2024

Brain and Behavior

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IntroductionPregnant women may need to undergo non‐obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane‐induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO‐induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO.MethodsPregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00–18:00 h) during GD15–21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti‐inflammatory markers and synaptic function‐related proteins were assessed using molecular biology methods.ResultsThe results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐alpha and a reduction in the hippocampal levels of IL‐10, synaptophysin, post‐synaptic density‐95, growth‐associated protein‐43, and brain‐derived neurotrophic factor.ConclusionOur findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.

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Neuroinflammaging underlies emotional disturbances and circadian rhythm disruption in young male senescence-accelerated mouse prone 8 mice

Cited by 9 publications

References 72 publications

Interleukin-1β Modulates Synaptic Transmission and Synaptic Plasticity During the Acute Phase of Sepsis in the Senescence-Accelerated Mouse Hippocampus

Interleukin-1β Modulates Synaptic Transmission and Synaptic Plasticity During the Acute Phase of Sepsis in the Senescence-Accelerated Mouse Hippocampus

Kampo formulas alleviate aging-related emotional disturbances and neuroinflammation in male senescence-accelerated mouse prone 8 mice

Subsequent maternal sleep deprivation aggravates cognitive impairment by modulating hippocampal neuroinflammatory responses and synaptic function in maternal isoflurane‐exposed offspring mice

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