Interplay between inflammation and neural plasticity: Both immune activation and suppression impair LTP and BDNF expression

Golia, M; Poggini, S.; Alboni, Silvia; Garofalo, Stefano; Albanese, N. Ciano; Viglione, Aurelia; Ajmone‐Cat, Maria Antonietta; St-Pierre, Abygaël; Brunello, Nicoletta; Limatola, Cristina; Branchi, Igor; Maggi, Laura

doi:10.1016/j.bbi.2019.07.003

Cited by 94 publications

(61 citation statements)

References 97 publications

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“…LPS may affect synaptic plasticity through different mechanisms. Previous studies have shown that LTP magnitude in hippocampal slices is acutely reduced after in vitro application of LPS [19,60], as well as 3 h after in vivo administration of a high dose of LPS (0.83 mg/kg) [4]; while a lower dose of LPS (0.33 mg/kg) does not affect LTP magnitude [4]. The authors suggested that high doses of LPS potently stimulate the release of IL-1 and TNF, which suppress LTP induction by inhibiting either presynaptic or postsynaptic calcium channels [19].…”

Section: Discussionmentioning

confidence: 99%

“…Clarke R. Raymond showed that moderate stimulation, similar to that used in our LTP induction protocol, typically induces a form of LTP dependent on the activation of NMDARs but uniquely sensitive to the IP3 receptor (IP3R) blockade. IP3Rs are primarily activated by Ins (1,4,5)P3 generated by phospholipase C (PLC)-linked group I mGluRs [18]. The coexistence of distinct activity-dependent systems of synaptic plasticity based on discrete Ca 2+ sources, such as NMDARs and mGluRs, has been recently described in the same synapses [33].…”

Section: Discussionmentioning

confidence: 99%

“…The administration of bacterial lipopolysaccharide (LPS) in different doses is commonly used as a model of bacterial infection [3]. By binding to toll-like receptor 4, LPS promotes pro-inflammatory gene expression in the cells of the immune and nervous systems, including the expression of cytokines such as interleukin-1β (IL-1β), interleukin 6 (IL-6), or tumor necrosis factor alpha (TNF-α), as well as the Pharmaceuticals 2020, 13 decreased expression of transforming growth factor beta (TGF-β), a cytokine with immunosuppressive and anti-inflammatory properties [4][5][6][7]. The administration of low doses of LPS in rats in early postnatal ontogenesis induced the accumulation of IL-6 in the juvenile period [8]; and later, in adulthood, the same doses resulted in impaired behavior in the fear conditioning test [2], and in the Morris water maze [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…The application of LPS in high doses in vivo and in vitro decreases the magnitude of LTP [4,19], most likely through an increase in pro-inflammatory cytokines [20]. It has been shown that LTP can either be promoted or prevented through the interference of TNF-α and IL-1β in the pathways controlling the molecular and structural synaptic changes indicative of LTP [20].…”

Section: Introductionmentioning

confidence: 99%

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Administration of Bacterial Lipopolysaccharide during Early Postnatal Ontogenesis Induces Transient Impairment of Long-Term Synaptic Plasticity Associated with Behavioral Abnormalities in Young Rats

et al. 2020

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Infectious diseases in early postnatal ontogenesis often result in cognitive impairments, particularly learning and memory. The essential foundation of learning and memory is long-term synaptic plasticity, which depends on N-methyl-D-aspartate (NMDA) receptors. In the present study, bacterial infection was modeled by treating rat pups with bacterial lipopolysaccharide (LPS, 25 µg/kg) three times, during either the first or the third week of life. These time points are critical for the maturation of NMDA receptors. We assessed the effects of LPS treatments on the properties of long-term potentiation (LTP) in the CA1 hippocampus of young (21-23 days) and adolescent (51-55 days) rats. LTP magnitude was found to be significantly reduced in both groups of young rats, which also exhibited investigative and motor behavior disturbances in the open field test. No changes were observed in the main characteristics of synaptic transmission, although the LTP induction mechanism was disturbed. In rats treated with LPS during the third week, the NMDA-dependent form of LTP was completely suppressed, and LTP switched to the Type 1 metabotropic glutamate receptor (mGluR1)-dependent form. These impairments of synaptic plasticity and behavior were temporary. In adolescent rats, no difference was observed in LTP properties between the control and experimental groups. Lastly, the investigative and motor behavior parameters in both groups of adult rats were similar.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Administration of Bacterial Lipopolysaccharide during Early Postnatal Ontogenesis Induces Transient Impairment of Long-Term Synaptic Plasticity Associated with Behavioral Abnormalities in Young Rats

et al. 2020

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“…These data indicate that miR-7 deficiency aggravates the pathology of BTI. It is well known that astrocytes and microglia play an important role in brain inflammation [28][29][30]. To further investigate the effect of miR-7 deficiency on the pathology of BTI, we observed the possible changes on astrocytes and microglia in brain tissue and found that the number of astrocytes and microglia were elevated in miR-7 def BTI model ( Fig.…”

Section: Mir-7 Deficiency Aggravates the Pathology Of Btimentioning

confidence: 92%

MicroRNA-7, synergizes with RORα, negatively controls the pathology of brain tissue inflammation

Yue

Zhao

Chen

et al. 2020

J Neuroinflammation

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Background: Accumulating evidence has documented that microRNA-7 (miR-7) plays an important role in the pathology of various diseases. However, the potential role of miR-7 in brain tissue inflammation (BTI) remains unclear. Methods: We detected the expression of miR-7 in LPS-induced murine BTI model and observed the possible effects of miR-7 deficiency on the pathology of BTI. To elucidate the mechanism, the target gene of miR-7 was screened out by Gene chip assay and its potential roles in BTI were evaluated by Western blot, immunofluorescence, and RNAi assay, respectively.Results: MiR-7 was upregulated in brain tissue in BTI mice and its deficiency could significantly aggravate the pathology of brain tissue. Moreover, RORα, a new target molecule of miR-7, was upregulated in brain tissue from miR-7 deficiency BTI mice. Of note, downregulation of RORα could remarkably exacerbate the pathology of brain tissue and elevate the transduction of NF-κB and ERK1/2 signaling pathways in brain tissue from miR-7 deficiency BTI mice. Furthermore, RORα and miR-7 were dominantly co-expressed in neurons of BTI mice. Finally, RORα synergized with miR-7 to control the inflammatory reaction of neuronal cells in response to LPS stimulation.Conclusions: MiR-7 expression is upregulated in BTI model. Moreover, miR-7 synergizes with its target gene RORα to control the inflammation reaction of neurons, thereby orchestrating the pathology of BTI.

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Nerolidol rescues hippocampal injury of diabetic rats through inhibiting NLRP3 inflammasome and regulation of MAPK/AKT pathway

Lei,

Li,

Liu

et al. 2024

BioFactors

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Despite the observation of diabetes‐induced brain tissue damage and impaired learning and memory, the underlying mechanism of damage remains elusive, and effective, targeted therapeutics are lacking. Notably, the NLRP3 inflammasome is highly expressed in the hippocampus of diabetic individuals. Nerolidol, a naturally occurring compound with anti‐inflammatory and antioxidant properties, has been identified as a potential therapeutic option for metabolic disorders. However, the ameliorative capacity of nerolidol on diabetic hippocampal injury and its underlying mechanism remain unclear. Network pharmacology and molecular docking was used to predict the signaling pathways and therapeutic targets of nerolidol for the treatment of diabetes. Then established a diabetic rat model using streptozotocin (STZ) combined with a high‐fat diet and nerolidol was administered. Morris water maze to assess spatial learning memory capacity. Hematoxylin and eosin and Nissl staining was used to detect neuronal damage in the diabetic hippocampus. Transmission electron microscopy was used to detect the extent of damage to mitochondria, endoplasmic reticulum (ER) and synapses. Immunofluorescence was used to detect GFAP, IBA1, and NLRP3 expression in the hippocampus. Western blot was used to detect apoptosis (Bcl‐2, BAX, and Cleaved‐Caspase‐3); synapses (postsynaptic densifying protein 95, SYN1, and Synaptophysin); mitochondria (DRP1, OPA1, MFN1, and MFN2); ER (GRP78, ATF6, CHOP, and caspase‐12); NLRP3 inflammasome (NLRP3, ASC, and caspase‐1); inflammatory cytokines (IL‐18, IL‐1β, and TNF‐α); AKT (P‐AKT); and mitogen‐activated protein kinase (MAPK) pathway (P‐ERK, P‐p38, and P‐JNK) related protein expression. Network pharmacology showed that nerolidol's possible mechanisms for treating diabetes are the MAPK/AKT pathway and anti‐inflammatory effects. Animal experiments demonstrated that nerolidol could improve blood glucose, blood lipids, and hippocampal neuronal damage in diabetic rats. Furthermore, nerolidol could improve synaptic, mitochondrial, and ER damage in the hippocampal ultrastructure of diabetic rats by potentially affecting synaptic, mitochondrial, and ER‐related proteins. Further studies revealed that nerolidol decreased neuroinflammation, NLRP3 and inflammatory factor expression in hippocampal tissue while also decreasing MAPK pathway expression and enhancing AKT pathway expression. However, nerolidol improves hippocampal damage in diabetic rats cannot be shown to improve cognitive function. In conclusion, our study reveals for the first time that nerolidol can ameliorate hippocampal damage, neuroinflammation, synaptic, ER, and mitochondrial damage in diabetic rats. Furthermore, we suggest that nerolidol may inhibit NLRP3 inflammasome and affected the expression of MAPK and AKT. These findings provide a new experimental basis for the use of nerolidol to ameliorate diabetes‐induced brain tissue damage and the associated disease.

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Interplay between inflammation and neural plasticity: Both immune activation and suppression impair LTP and BDNF expression

Cited by 94 publications

References 97 publications

Administration of Bacterial Lipopolysaccharide during Early Postnatal Ontogenesis Induces Transient Impairment of Long-Term Synaptic Plasticity Associated with Behavioral Abnormalities in Young Rats

Administration of Bacterial Lipopolysaccharide during Early Postnatal Ontogenesis Induces Transient Impairment of Long-Term Synaptic Plasticity Associated with Behavioral Abnormalities in Young Rats

MicroRNA-7, synergizes with RORα, negatively controls the pathology of brain tissue inflammation

Nerolidol rescues hippocampal injury of diabetic rats through inhibiting NLRP3 inflammasome and regulation of MAPK/AKT pathway

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