Anticonvulsant-like effect of thromboxane receptor agonist U-46619 against pentylenetetrazol-induced seizures

Freitas, Mayara Lutchemeyer de; Mello, Fernanda Kulinski; Souza, Thaíze Lopes de; Grauncke, Ana Claudia Beck; Fighera, Michele Rechia; Royes, Luiz Fernando Freire; Furian, Ana Flávia; Oliveira, Mauro Schneider

doi:10.1016/j.eplepsyres.2018.08.003

Cited by 3 publications

(3 citation statements)

References 37 publications

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“…In contrast, none of the non-DREADD WT control animals showed any HA-tag label in PV+ cells. The labeling of PV+ cells in this study was consistent with that of other published studies (del Río and DeFelipe, 1994;Tamamaki et al, 2003;Dávid et al, 2007;Fishell, 2007;Xu et al, 2010). The efficacy and specificity of this double transgenic approach for expressing DREADD receptors in feed-forward inhibitory PV+ interneurons was higher than that reported for viral-mediated DREADD expression in PV-Cre animals.…”

Section: Discussionsupporting

confidence: 91%

Chemogenetic Activation of Feed-Forward Inhibitory Parvalbumin-Expressing Interneurons in the Cortico-Thalamocortical Network During Absence Seizures

Panthi

Leitch

2021

Front. Cell. Neurosci.

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Parvalbumin-expressing (PV+) interneurons are a subset of GABAergic inhibitory interneurons that mediate feed-forward inhibition (FFI) within the cortico-thalamocortical (CTC) network of the brain. The CTC network is a reciprocal loop with connections between cortex and thalamus. FFI PV+ interneurons control the firing of principal excitatory neurons within the CTC network and prevent runaway excitation. Studies have shown that generalized spike-wave discharges (SWDs), the hallmark of absence seizures on electroencephalogram (EEG), originate within the CTC network. In the stargazer mouse model of absence epilepsy, reduced FFI is believed to contribute to absence seizure genesis as there is a specific loss of excitatory α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at synaptic inputs to PV+ interneurons within the CTC network. However, the degree to which this deficit is directly related to seizure generation has not yet been established. Using chemogenetics and in vivo EEG recording, we recently demonstrated that functional silencing of PV+ interneurons in either the somatosensory cortex (SScortex) or the reticular thalamic nucleus (RTN) is sufficient to generate absence-SWDs. Here, we used the same approach to assess whether activating PV+ FFI interneurons within the CTC network during absence seizures would prevent or reduce seizures. To target these interneurons, mice expressing Cre recombinase in PV+ interneurons (PV-Cre) were bred with mice expressing excitatory Gq-DREADD (hM3Dq-flox) receptors. An intraperitoneal dose of pro-epileptic chemical pentylenetetrazol (PTZ) was used to induce absence seizure. The impact of activation of FFI PV+ interneurons during seizures was tested by focal injection of the “designer drug” clozapine N-oxide (CNO) into either the SScortex or the RTN thalamus. Seizures were assessed in PVCre/Gq-DREADD animals using EEG/video recordings. Overall, DREADD-mediated activation of PV+ interneurons provided anti-epileptic effects against PTZ-induced seizures. CNO activation of FFI either prevented PTZ-induced absence seizures or suppressed their severity. Furthermore, PTZ-induced tonic-clonic seizures were also reduced in severity by activation of FFI PV+ interneurons. In contrast, administration of CNO to non-DREADD wild-type control animals did not afford any protection against PTZ-induced seizures. These data demonstrate that FFI PV+ interneurons within CTC microcircuits could be a potential therapeutic target for anti-absence seizure treatment in some patients.

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Section: Discussionsupporting

confidence: 91%

Chemogenetic Activation of Feed-Forward Inhibitory Parvalbumin-Expressing Interneurons in the Cortico-Thalamocortical Network During Absence Seizures

Panthi

Leitch

2021

Front. Cell. Neurosci.

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“…The animals were randomly divided into different groups of eight mice each, and curcumin was injected intraperitoneally into the mice daily after recovery from anesthesia. Some mice were administered a contralateral intracerebroventricular injection of a solution containing either U-46619 (10 mM) (Freitas et al, 2018) or dimethyl sulphoxide (DMSO) at 1 hr before curcumin injection.…”

Section: Experimental Tbi Modelmentioning

confidence: 99%

“…Additionally, U‐46619 has been used in various brain tissue studies. It was shown to increase the latency of myoclonic seizures and tonic–clonic seizures induced by pentylenetetrazol (Freitas et al, 2018). U‐46619 reverses the inhibitory effect of recombinant CC16 on NLRP3/CASPASE‐1‐induced apoptosis in the septic brain of neonatal rats (Zhou et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Curcumin suppress inflammatory response in traumatic brain injury via p38/MAPK signaling pathway

Duan

Yang

et al. 2022

Phytotherapy Research

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Traumatic brain injury (TBI) is a common disease worldwide with a high mortality and disability rate and is closely related to the inflammatory response. However, the molecular mechanisms during the pathophysiological responses are not completely understood. This study was conducted to investigate the protective effect of curcumin on TBI and the molecular mechanisms of the p38/MAPK signal pathway. We found that curcumin remarkably ameliorated secondary brain injury after TBI, including effects on the neurological severity score and inflammation. After injection of curcumin, the neurological function score of mice decreased significantly. Curcumin exhibited antiinflammatory pharmacological effects, as reflected by inhibition of inflammatory factors (e.g., interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF]α). Additionally, curcumin notably reduced the expression of p-p38 according to western blotting and immunohistochemical analyses. In conclusion, curcumin remarkably alleviated posttraumatic inflammation and thus shows potential for treating inflammation associated with TBI.

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G protein-coupled receptors in acquired epilepsy: Druggability and translatability

Nguyen

Jiang

2019

Progress in Neurobiology

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Anticonvulsant-like effect of thromboxane receptor agonist U-46619 against pentylenetetrazol-induced seizures

Cited by 3 publications

References 37 publications

Chemogenetic Activation of Feed-Forward Inhibitory Parvalbumin-Expressing Interneurons in the Cortico-Thalamocortical Network During Absence Seizures

Chemogenetic Activation of Feed-Forward Inhibitory Parvalbumin-Expressing Interneurons in the Cortico-Thalamocortical Network During Absence Seizures

Curcumin suppress inflammatory response in traumatic brain injury via p38/MAPK signaling pathway

G protein-coupled receptors in acquired epilepsy: Druggability and translatability

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