The effect of IL-1β on synaptophysin expression and electrophysiology of hippocampal neurons through the PI3K/Akt/mTOR signaling pathway in a rat model of mesial temporal lobe epilepsy

Xiao, Zunqi; Peng, Jing; Wu, Liwen; Arafat, Ahmed; Yin, Fei

doi:10.1080/01616412.2017.1312070

Cited by 21 publications

(13 citation statements)

References 53 publications

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“…Synaptophysin (Syn) and postsynaptic density protein 95 (PSD-95) are an important marker of synaptic plasticity in the brain. Syn is located in presynaptic vesicles and is closely related to the structure and function of synapses (28). PSD-95 is extensively studied in synaptic plasticity (29).…”

Section: Introductionmentioning

confidence: 99%

Exercise Intervention Promotes the Growth of Synapses and Regulates Neuroplasticity in Rats With Ischemic Stroke Through Exosomes

et al. 2021

Front. Neurol.

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Background: Stroke is the leading cause of death and disability. Exercise produces neuroprotection by improving neuroplasticity. Exercise can induce exosome production. According to several studies, exosomes are involved in repairing brain function, but the relationship and mechanism of exercise, exosomes, and neuroprotection have not been elucidated. This study intends to explore the relationship and potential mechanism by observing the changes in the exosome level, infarct volume, neurological function and behavioral scores, synapses, and corticospinal tract (CST).Methods: Rats were randomly divided into four groups: a sham operation (SHAM) group, middle cerebral artery occlusion (MCAO) with sedentary intervention (SED-MCAO) group, MCAO with exercise intervention (EX-MCAO) group, and MCAO with exercise intervention and exosome injection (EX-MCAO-EXO) group. The exercise intervention was started 1 day after MCAO and lasted for 4 weeks. All rats were assessed using the modified neurological severity score (mNSS). The levels of exosomes in serum and brain, gait analysis, and magnetic resonance scan were performed 1 and 4 weeks after the intervention. After 4 weeks of intervention, the number of synapses, synaptophysin (Syn), and postsynaptic density protein 95(PSD-95) expression was detected.Results: After 4 weeks of intervention, (1) the EX-MCAO and EX-MCAO-EXO groups showed higher serum exosome (pEX−MCAO = 0.000, pEX−MCAO−EXO = 0.000) and brain exosome (pEX−MCAO = 0.001, pEX−MCAO−EXO = 0.000) levels than the SED-MCAO group, of which the EX-MCAO group had the highest serum exosome (p = 0.000) and the EX-MCAO-EXO group had the highest brain exosome (p = 0.03) levels. (2) The number of synapses in the EX-MCAO (p = 0.032) and EX-MCAO-EXO groups (p = 0.000) was significantly higher than that in the SED-MCAO group. The EX-MCAO-EXO group exhibited a greater number of synapses than the EX-MCAO (p = 0.000) group. (3) The synaptic plasticity-associated proteins were expressed significantly higher in the EX-MCAO (pSyn = 0.010, pPSD−95 = 0.044) and EX-MCAO-EXO (pSyn = 0.000, pPSD−95 = 0.000) groups than in the SED-MCAO group, and the EX-MCAO-EXO group (pSyn = 0.000, pPSD−95 = 0.046) had the highest expression. (4) Compared with the SED-MCAO group, the EX-MCAO group had significantly improved infarct volume ratio (p = 0.000), rFA value (p = 0.000), and rADC (p = 0.000). Compared with the EX-MCAO group, the EX-MCAO-EXO group had a significantly improved infarct volume ratio (p = 0.000), rFA value (p = 0.000), and rADC value (p = 0.001). (5) Compared with the SED-MCAO group, the EX-MCAO group (p = 0.001) and EX-MCAO-EXO group (p = 0.000) had significantly lower mNSS scores and improved gait. (6) The brain exosome levels were negatively correlated with the mNSS score, infarct volume ratio, and rADC value and positively correlated with the rFA value, Syn, and PSD-95 expression. The serum and brain exosome levels showed a positive correlation.Conclusions: Exercise intervention increases the serum exosome level in MCAO rats, which are recruited into the brain, leading to improved synaptic growth and CST integrity, a reduced infarct volume, and improved neurological function and gait.

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Section: Introductionmentioning

confidence: 99%

Exercise Intervention Promotes the Growth of Synapses and Regulates Neuroplasticity in Rats With Ischemic Stroke Through Exosomes

et al. 2021

Front. Neurol.

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“…Moreover, these changes could lead to the infiltration of inflammatory cells from the periphery to the brain, which can aggravate inflammation and promote hyperexcitability, excitotoxicity, and epileptogenesis ( Figure 2 ) ( 43 ). IL-1β can also stimulate synaptophysin expression and epileptiform discharges via the PI3K/Akt/mTOR signaling pathway to induce seizure generation in an animal model with temporal lobe epilepsy ( 53 ). Furthermore, the IL-1β/IL-1R1 signaling pathway promotes glial activation, proliferation, and cytokine release, which leads to an amplified inflammatory response and increases the risk of seizures and brain damage ( 54 ).…”

Section: Mechanisms Underlying Il-1β/il-1r1-mediated Neuroimmune Infl...mentioning

confidence: 99%

Role of HMGB1/TLR4 and IL-1β/IL-1R1 Signaling Pathways in Epilepsy

et al. 2022

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Epilepsy is a chronic disorder of the nervous system characterized by recurrent seizures. Inflammation is one of the six major causes of epilepsy, and its role in the pathogenesis of epilepsy is gaining increasing attention. Two signaling pathways, the high mobility group box-1 (HMGB1)/toll-like receptor 4 (TLR4) and interleukin-1β (IL-1β)/interleukin-1 receptor 1 (IL-1R1) pathways, have become the focus of research in recent years. These two signaling pathways have potential as biomarkers in the prediction, prognosis, and targeted therapy of epilepsy. This review focuses on the association between epilepsy and the neuroinflammatory responses mediated by these two signaling pathways. We hope to contribute further in-depth studies on the role of HMGB1/TLR4 and IL-1β/IL-1R1 signaling in epileptogenesis and provide insights into the development of specific agents targeting these two pathways.

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“…The phosphorylation of NMDAR will then increase the Ca 2+ influx in neurons [41]. In hippocampal neurons, IL-1β could increase synaptophysin (SYN) expression by stimulating the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) /mammalian target of rapamycin (mTOR) pathway, and SYN has been found to be related to recurrent seizures in a lithium-pilocarpine-induced MTLE rat model [42]. On the other hand, the activation of IL-1R1 may result in the fast onset of MyD88dependent, ceramide-mediated activation of the Srcfamily tyrosine kinases in the preoptic area/anterior hypothalamus, which can influence the A-type K + currents in neurons and consequently reduce the synaptic release of GABA [39].…”

Section: Cytokines: Multiple Players In Epileptogenesismentioning

confidence: 99%

“…There are numerous upstream modulators of mTOR, including PI3K, AKT (PKB), and epidermal growth factor receptor (EGFR) [112]. As noted above, some inflammatory mediators (such as IL-1β and ROS) can function through the mTOR pathway in epileptogenesis, and IL-1β has been found to participate in epilepsy by activating mTOR upstream regulators [35,42]. The mTOR pathway is critical for biological processes of the CNS, including cortical development, axonal and dendritic morphology, immune responses, neurotransmitter expression, ion channel expression, synaptic plasticity, cognition, and behavior [113,114].…”

Section: Rosmentioning

confidence: 99%

The role of inflammation in epileptogenesis

Meng

Yao

2020

Acta Epileptologica

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Epilepsy is a chronic neurological disorder that has an extensive impact on a patient’s life. Accumulating evidence has suggested that inflammation participates in the progression of spontaneous and recurrent seizures. Pro-convulsant incidences can stimulate immune cells, augment the release of pro-inflammatory cytokines, elicit neuronal excitation as well as blood-brain barrier (BBB) dysfunction, and finally trigger the generation or recurrence of seizures. Understanding the pathogenic roles of inflammatory mediators, including inflammatory cytokines, cells, and BBB, in epileptogenesis will be beneficial for the treatment of epilepsy. In this systematic review, we performed a literature search on the PubMed database using the following keywords: “epilepsy” or “seizures” or “epileptogenesis”, and “immunity” or “inflammation” or “neuroinflammation” or “damage-associated molecular patterns” or “cytokines” or “chemokines” or “adhesion molecules” or “microglia” or “astrocyte” or “blood-brain barrier”. We summarized the classic inflammatory mediators and their pathogenic effects in the pathogenesis of epilepsy, based on the most recent findings from both human and animal model studies.

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The effect of IL-1β on synaptophysin expression and electrophysiology of hippocampal neurons through the PI3K/Akt/mTOR signaling pathway in a rat model of mesial temporal lobe epilepsy

Cited by 21 publications

References 53 publications

Exercise Intervention Promotes the Growth of Synapses and Regulates Neuroplasticity in Rats With Ischemic Stroke Through Exosomes

Exercise Intervention Promotes the Growth of Synapses and Regulates Neuroplasticity in Rats With Ischemic Stroke Through Exosomes

Role of HMGB1/TLR4 and IL-1β/IL-1R1 Signaling Pathways in Epilepsy

The role of inflammation in epileptogenesis

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