Endocannabinoid-dependent protection against kainic acid-induced long-term alteration of brain oscillations in guinea pigs

Shubina, Liubov; Алиев, Р. Р.; Kitchigina, Valentina F.

doi:10.1016/j.brainres.2017.02.003

Cited by 18 publications

(11 citation statements)

References 127 publications

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“…These data together attribute the AM5206 protective response, which specifically targets FAAH to modulate endogenous cannabinoid signaling (Naidoo et al 2011). Noteworthy, evidence of protective responses by the endocannabinoid pathway was also shown in other studies of excitotoxicity (Karanian et al 2005b;Sagar et al 2010;Naidoo et al 2011Naidoo et al , 2012Shubina et al 2017).…”

Section: Resultssupporting

confidence: 53%

Inhibitor of Endocannabinoid Deactivation Protects Against In Vitro and In Vivo Neurotoxic Effects of Paraoxon

et al. 2017

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The anticholinesterase paraoxon (Pxn) is related to military nerve agents that increase acetylcholine levels, trigger seizures, and cause excitotoxic damage in the brain. In rat hippocampal slice cultures, high-dose Pxn was applied resulting in a presynaptic vulnerability evidenced by a 64% reduction in synapsin IIb (syn IIb) levels, whereas the postsynaptic protein GluR1 was unchanged. Other signs of Pxn-induced cytotoxicity include the oxidative stress-related production of stable 4-hydroxynonenal (4-HNE)-protein adducts. Next, the Pxn toxicity was tested for protective effects by the fatty acid amide hydrolase (FAAH) inhibitor AM5206, a compound linked to enhanced repair signaling through the endocannabinoid pathway. The Pxn-mediated declines in syn IIb and synaptophysin were prevented by AM5206 in the slice cultures. To test if the protective results in the slice model translate to an in vivo model, AM5206 was injected i.p. into rats, followed immediately by subcutaneous Pxn administration. The toxin caused a pathogenic cascade initiated by seizure events, leading to presynaptic marker decline and oxidative changes in the hippocampus and frontal cortex. AM5206 exhibited protective effects including the reduction of seizure severity by 86%, and improving balance and coordination measured 24 h post-insult. As observed in hippocampal slices, the FAAH inhibitor also prevented the Pxn-induced loss of syn IIb in vivo. In addition, the AM5206 compound reduced the 4-HNE modifications of proteins and the β1 integrin activation events both in vitro and in vivo. These results indicate that Pxn exposure produces oxidative and synaptic toxicity that leads to the behavioral deficits manifested by the neurotoxin. In contrast, the presence of FAAH inhibitor AM5206 offsets the pathogenic cascade elicited by the Pxn anticholinesterase.

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Section: Resultssupporting

confidence: 53%

Inhibitor of Endocannabinoid Deactivation Protects Against In Vitro and In Vivo Neurotoxic Effects of Paraoxon

et al. 2017

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“…In accordance with our results, some studies have shown neuroprotective effects of AM404 on different models. AM404 has been found to protect against neuronal death in an animal model of ischemia (Zani et al, 2007) and epilepsy (Shubina et al, 2017). Huang et al (2019) demonstrated the treatment with AM404 significantly induced neuroprotection in hippocampal neuronal culture.…”

Section: Discussionmentioning

confidence: 97%

“…Moreover, AM404 has been described to attenuate seizures from epilepsy models using pentylenetetrazole (PTZ; Manna and Umathe, 2012) or kainic acid (Shubina et al, 2015(Shubina et al, , 2017. Manna and Umathe (2012) further demonstrated that in an epilepsy model using PTZ, the protective effects of AM404 involved CB1 but not TRPV1 receptors.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of AM404 Against NMDA-Induced Hippocampal Excitotoxicity

Saliba

Bonifacino

Serchov

et al. 2019

Front. Cell. Neurosci.

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Different studies have demonstrated that inflammation and alterations in glutamate neurotransmission are two events contributing to the pathophysiology of neurodegenerative or neurological disorders. There are evidences that N-arachidonoylphenolamine (AM404), a cannabinoid system modulator and paracetamol metabolite, modulates inflammation and exerts neuroprotective effects on Huntington's (HD) and Parkinson's diseases (PD), and ischemia. However, the effects of AM404 on the production of inflammatory mediators and excitotoxicity in brain tissue stimulated with N-methyl-D-aspartic acid (NMDA) are not elucidated. In this present study, we investigated the effects of AM404 on the production of inflammatory mediators and neuronal cell death induced by NMDA in organotypic hippocampal slices cultures (OHSC) using qPCR, western blot (WB), and immunohistochemistry. Moreover, to comprehend the mechanism of excitotoxicity, we evaluated the effects of AM404 on glutamate release in hippocampal synaptosomes and the NMDA-induced calcium responses in acute hippocampal slices. Our results showed that AM404 led to a significant decrease in cell death induced by NMDA, through a mechanism possibly involving the reduction of glutamate release and the calcium ions responses. Furthermore, it decreased the expression of the interleukin (IL)-1β. This study provides new significant insights about the anti-inflammatory and neuroprotection effects of AM404 on NMDA-induced excitotoxicity. To understand the effects of AM404 in these processes might contribute to the therapeutic potential of AM404 in diseases with involvement of neuroinflammation and neurodegeneration and might lead to a possible future treatment of neurodegenerative diseases.

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“…The correct balance of neuronal activation is necessary for normal brain function and to avoid the harsh effects of excitotoxicity. Indeed, the ECS is a neuromodulatory system that has been proposed as neuroprotective [53][54][55]. For example, following epileptiform producing injections of kainic acid, mice that did not express CB1 receptors in principal glutamatergic neurons (Glu-CB1-KO mice) suffered from more severe seizures than wild-type mice [53,54].…”

Section: Glutamatergic Transmissionmentioning

confidence: 99%

Cannabinoid control of hippocampal functions: the where matters

et al. 2021

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In the brain, hippocampal circuits are crucial for cognitive performance (e.g., memory) and deeply affected in pathological conditions (e.g., epilepsy, Alzheimer). Specialized molecular mechanisms regulate different cell types underlying hippocampal circuitries functions. Among them, cannabinoid receptors exhibit various roles depending on the cell type (e.g., neuron, glial cell) or subcellular organelle (e.g., mitochondria). Determining the site of action and precise mechanisms triggered by cannabinoid receptor activation at a local cellular and subcellular level helps us understand hippocampal pathophysiological states. In doing so, past and current research have advanced our knowledge of cannabinoid functions and proposed novel routes for potential therapeutics. By outlining these data in this work, we aim to showcase current findings and highlight the pathophysiological impact of the cannabinoid receptor type 1 (CB1) localization/ activation in hippocampal circuits.

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Endocannabinoid-dependent protection against kainic acid-induced long-term alteration of brain oscillations in guinea pigs

Cited by 18 publications

References 127 publications

Inhibitor of Endocannabinoid Deactivation Protects Against In Vitro and In Vivo Neurotoxic Effects of Paraoxon

Inhibitor of Endocannabinoid Deactivation Protects Against In Vitro and In Vivo Neurotoxic Effects of Paraoxon

Neuroprotective Effect of AM404 Against NMDA-Induced Hippocampal Excitotoxicity

Cannabinoid control of hippocampal functions: the where matters

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