Short-term memory impairment following recovery from systemic inflammation induced by lipopolysaccharide in mice DOI Creative Commons
Kohei Morimoto, S. WATANUKI, Ryota Eguchi

и другие.

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Окт. 18, 2023

The relationship between neuroinflammation and mental disorders has been recognized investigated for over 30 years. Diseases of systemic or peripheral inflammation, such as sepsis, peritonitis, infection, are associated with increased risk neuroinflammation. To elucidate the pathogenesis, administration lipopolysaccharide (LPS) in mice is often used. LPS-injected exhibit behavioral abnormalities glial activation. However, these studies unlikely to recapitulate clinical pathophysiology human patients, most focus on acute inflammatory response symptoms occurring within 24 h LPS injection. In this study, we effects following recovery from investigate mechanisms pathogenesis. Several tests were performed mice, assess neuroinflammation, time course morphological change expression factors neurons, astrocytes, microglia investigated. At 7 days post-LPS injection, exhibited short-term memory impairment accompanied by suppression neuronal activity increases morphologically immature spines. Glial cells transiently activated hippocampus concomitant upregulation microglial phagocytosis marker CD68 3 after Here show that transient cell activation phase affects behavior symptoms. These findings provide novel insights using LPS-induced inflammation model will contribute development treatments etiology.

Язык: Английский

Cytokines as emerging regulators of central nervous system synapses DOI Creative Commons
Frauke Zipp, Stefan Bittner, Dorothy P. Schafer

и другие.

Immunity, Год журнала: 2023, Номер 56(5), С. 914 - 925

Опубликована: Май 1, 2023

Язык: Английский

Процитировано

85
The Key Drivers of Brain Injury by Systemic Inflammatory Responses after Sepsis: Microglia and Neuroinflammation DOI Creative Commons

Yuewen Xin,

Mi Tian, Shuixiang Deng

и другие.

Molecular Neurobiology, Год журнала: 2022, Номер 60(3), С. 1369 - 1390

Опубликована: Ноя. 29, 2022

Abstract Sepsis is a leading cause of intensive care unit admission and death worldwide. Most surviving patients show acute or chronic mental disorders, which are known as sepsis-associated encephalopathy (SAE). Although accumulating studies in the past two decades focused on pathogenesis SAE, systematic review retrospective exclusively focuses inflammatory mechanisms SAE has been lacking yet. This summarizes recent advance field neuroinflammation sheds light activation microglia SAE. Activation predominates neuroinflammation. As gene expression profile changes, heterogeneous characterizations throughout all stages Here, we summarize systemic inflammation following sepsis also relationship microglial diversity Moreover, collection neuroinflammation-related dysfunction reviewed to illustrate possible for In addition, promising pharmacological non-pharmacological therapeutic strategies, especially those target microglia, concluded final part this review. Collectively, clarification vital between SAE-related disorders would significantly improve our understanding pathophysiological therefore provide potential targets therapies aimed at inhibiting

Язык: Английский

Процитировано

44
Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortex DOI Creative Commons
Yong He, Yue Wang,

Heming Yu

и другие.

Pharmacological Research, Год журнала: 2023, Номер 191, С. 106717 - 106717

Опубликована: Март 21, 2023

Neuroinflammation is tightly associated with onset of depression. The nuclear receptor related 1 protein (Nurr1, also called Nr4a2), its roles in dopaminergic neurons well understood, which can alleviate inflammation. Nevertheless, potential effects Nr4a2 on neuroinflammation depression still remains unclear. Chronic lipopolysaccharides (LPS) stress induced depressive-behaviors were confirmed via behavioral tests. Differentially expressed genes detected by using RNA-sequencing. anterior cingulate cortex (ACC) tissues collected for biochemical experiments. Golgi-Cox staining and virus labeling used to evaluate the dendritic spines. We applied fluoxetine (FLX) amodiaquine dihydrochloride (AQ, a highly selective agonist Nr4a2) mice. Overexpression experiments performed injecting AAV-Nr4a2-EGFP into ACC. Chemogenetic activation CamkII hM3Dq virus. Mice treated LPS displayed depressive- anxiety-like behaviors. reduction FosB rescued pretreatment FLX or AQ. More importantly, LPS-induced behavior deficits mice alleviated treatment pharmacological expression Nr4a2. Meanwhile, enhancing level could improve spines loss neuron morphological changes microglia. ACC reversed behaviors caused administration. Activation robustly increase deficits. Our findings demonstrate that may regulate depressive-like alleviating impairment morphology function microglia chronic neuroinflammation.

Язык: Английский

Процитировано

33
Real-time mechanisms of exacerbated synaptic remodeling by microglia in acute models of systemic inflammation and tauopathy DOI Creative Commons
Carla Cangalaya, Susanne Wegmann, Wei‐Lun Sun

и другие.

Brain Behavior and Immunity, Год журнала: 2023, Номер 110, С. 245 - 259

Опубликована: Март 9, 2023

Remodeling of synapses by microglia is essential for synaptic plasticity in the brain. However, during neuroinflammation and neurodegenerative diseases, can induce excessive loss, although precise underlying mechanisms are unknown. To directly observe microglia-synapse interactions under inflammatory conditions, we performed vivo two-photon time-lapse imaging after bacterial lipopolysaccharide administration to model systemic inflammation, or inoculation Alzheimer's disease (AD) brain extracts disease-associated neuroinflammatory microglial response. Both treatments prolonged microglia-neuron contacts, decreased basal surveillance promoted remodeling response stress induced focal single-synapse photodamage. Spine elimination correlated with expression complement system/phagocytic proteins occurrence filopodia. Microglia were observed contacting spines, then stretching phagocytosing spine head Thus, stimuli exacerbated through contact spines 'tagged'

Язык: Английский

Процитировано

20
The impact of ammonia and microcystin-LR on neurobehavior and glutamate/gamma-aminobutyric acid balance in female zebrafish (Danio rerio): ROS and inflammation as key pathways DOI

Ya He,

Kang Ou-Yang,

Hui Yang

и другие.

The Science of The Total Environment, Год журнала: 2024, Номер 920, С. 170914 - 170914

Опубликована: Фев. 12, 2024

Язык: Английский

Процитировано

8
Hippocampal GPR35 is involved in the depression-like behaviors induced by inflammation and mediates the antidepressant effects of fluoxetine in mice DOI

Kang Xu,

Zhi Xie, Yan Yang

и другие.

Brain Behavior and Immunity, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

1
Bifidobacterium breve Bif11 supplementation improves depression-related neurobehavioural and neuroinflammatory changes in the mouse DOI
Gunuputi Sushma, Bhupesh Vaidya, Shikha Sharma

и другие.

Neuropharmacology, Год журнала: 2023, Номер 229, С. 109480 - 109480

Опубликована: Март 1, 2023

Язык: Английский

Процитировано

17
LPS priming before plaque deposition impedes microglial activation and restrains Aβ pathology in the 5xFAD mouse model of Alzheimer’s disease DOI Creative Commons
Yiyi Yang, Marta García-Cruzado,

Hairuo Zeng

и другие.

Brain Behavior and Immunity, Год журнала: 2023, Номер 113, С. 228 - 247

Опубликована: Июль 11, 2023

Microglia have an innate immunity memory (IIM) with divergent functions in different animal models of neurodegenerative diseases, including Alzheimer's disease (AD). AD is characterized by chronic neuroinflammation, neurodegeneration, tau tangles and β-amyloid (Aβ) deposition. Systemic inflammation has been implicated contributing to the progression AD. Multiple reports demonstrated unique microglial signatures mouse patients. However, proteomic profiles microglia modified IIM not well-documented model. Therefore, present study, we investigate whether lipopolysaccharide (LPS)-induced pre-clinical stage alters responses shapes neuropathology. We accomplished this priming 5xFAD wild-type (WT) mice LPS injection at 6 weeks (before robust development plaques). 140 days later, evaluated morphology, activation, barrier around Aβ, Aβ deposition both primed unprimed mice. Priming induced decreased soma size reduced colocalization PSD95 Synaptophysin retrosplenial cortex. appeared increase phagocytosis resulting fewer Thioflavin S+ fibrils dentate gyrus. RIPA-soluble 40 42 were significantly Primed-5xFAD leading a smaller MOAB2+ plaques prefrontal also found that Aβ-associated less activated number. After priming, observed improved performance 5xFAD. To further elucidate molecular mechanism underlying these changes, performed quantitative analysis bone marrow monocytes. A specific pattern proteome was revealed These results suggest imprint display distinctive phenotype highlight potential for beneficial adaption when intervention occurs

Язык: Английский

Процитировано

17
Microglia modulate TNFα‐mediated synaptic plasticity DOI Creative Commons
Dimitrios Kleidonas, M. Kirsch, Geoffroy Andrieux

и другие.

Glia, Год журнала: 2023, Номер 71(9), С. 2117 - 2136

Опубликована: Май 19, 2023

The pro-inflammatory cytokine tumor necrosis factor α (TNFα) tunes the capacity of neurons to express synaptic plasticity. It remains, however, unclear how TNFα mediates positive (=change) and negative (=stability) feedback mechanisms. We assessed effects on microglia activation transmission onto CA1 pyramidal mouse organotypic entorhino-hippocampal tissue cultures. mediated changes in excitatory inhibitory neurotransmission a concentration-dependent manner, where low concentration strengthened glutamatergic via accumulation GluA1-only-containing AMPA receptors higher increased inhibition. latter induced as well. However, activated, homeostatic adjustment synapses, that is, an initial increase strength at 3 h returned baseline within 24 h, while increased. In microglia-depleted cultures, strengthening triggered by high levels persisted impact was still observed dependent its concentration. These findings underscore essential role TNFα-mediated They suggest mediate homeostasis, mechanisms, which may affect ability further plasticity, thereby emphasizing importance gatekeepers change stability.

Язык: Английский

Процитировано

16
Overexpression of Sirt6 ameliorates sleep deprivation induced-cognitive impairment by modulating glutamatergic neuron function DOI Creative Commons

Jinpiao Zhu,

Chang Chen,

Zhen Li

и другие.

Neural Regeneration Research, Год журнала: 2023, Номер 18(11), С. 2449 - 2458

Опубликована: Март 11, 2023

Sleep benefits the restoration of energy metabolism and thereby supports neuronal plasticity cognitive behaviors. Sirt6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator because it modulates various transcriptional regulators metabolic enzymes. The aim this study was to investigate influence on cerebral function after chronic sleep deprivation (CSD). We assigned C57BL/6J mice control or two CSD groups subjected them AAV2/9-CMV-EGFP AAV2/9-CMV-Sirt6-EGFP infection in prelimbic cortex (PrL). then assessed functional connectivity (FC) using resting-state MRI, neuron/astrocyte kinetics analysis; dendritic spine densities sparse-labeling; miniature excitatory postsynaptic currents (mEPSCs) action potential (AP) firing rates whole-cell patch-clamp recordings. In addition, we evaluated cognition via comprehensive set behavioral tests. Compared with controls, significantly decreased (P < 0.05) PrL CSD, accompanied by deficits FC between accumbens nucleus, piriform cortex, motor somatosensory olfactory tubercle, insular cerebellum. overexpression reversed CSD-induced impairment reduced FC. Our analysis [1-13C] glucose [2-13C] acetate showed Glu4 GABA2 synthesis, which could be fully restored forced expression. Furthermore, decreases AP well frequency amplitude mEPSCs pyramidal neurons. These data indicate can improve regulating PrL-associated network, metabolism, glutamatergic neurotransmission. Thus, activation may have novel strategy for treating disorder-related diseases.

Язык: Английский

Процитировано

14