Morphological and molecular correlates of altered hearing sensitivity in the genetically audiogenic seizure-prone hamster GASH/Sal

Sánchez-Benito, David; Hyppolito, Miguel Ângelo; Alvarez-Morujo, A; López, Dolores E.; Gómez-Nieto, Ricardo

doi:10.1016/j.heares.2020.107973

Cited by 11 publications

(18 citation statements)

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“…As occurred in other AGS rodent models, activation of the auditory pathway is required for seizure development in the GASH/Sal model (Garcia-Cairasco, 2002;Muñoz et al, 2017). In fact, the innate AGS susceptibility of the GASH/Sal model lies in an upward spread of abnormal glutamatergic transmission throughout the primary acoustic pathway to the inferior colliculus, a critical integration center in the auditory midbrain that is considered the epileptogenic region (Sánchez-Benito et al, 2020). Furthermore, recent studies have found disrupted gene expression profiles in the inferior colliculus of the GASH/Sal under free-seizure conditions and after sound-induced seizures that are associated with seizure susceptibility and altered regulation of neuronal excitability (López-López et al, 2017;Damasceno et al, 2020;Díaz-Casado et al, 2020;Díaz-Rodríguez et al, 2020).…”

Section: Introductionmentioning

confidence: 92%

Behavioral and Molecular Effects Induced by Cannabidiol and Valproate Administration in the GASH/Sal Model of Acute Audiogenic Seizures

Cabral-Pereira

Sánchez-Benito

Díaz-Rodríguez

et al. 2021

Front. Behav. Neurosci.

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Despite evidence that supports cannabidiol (CBD) as an anticonvulsant agent, there remains controversy over the antiseizure efficacy, possible adverse effects, and synergistic interactions with classic antiepileptics such as valproate (VPA). The genetic audiogenic seizure hamster from the University of Salamanca (GASH/Sal) is a reliable experimental model of generalized tonic–clonic seizures in response to intense sound stimulation. The present study examines the behavioral and molecular effects of acute and chronic intraperitoneal administrations of VPA (300 mg/kg) and CBD (100 mg/kg) on the GASH/Sal audiogenic seizures, as well as the coadministration of both drugs. The GASH/Sal animals were examined prior to and after the corresponding treatment at 45 min, 7 days, and 14 days for seizure severity and neuroethology, open-field behaviors, body weight variations, and various hematological and biochemical parameters. Furthermore, the brain tissue containing the inferior colliculus (so-called epileptogenic nucleus) was processed for reverse transcription–quantitative polymerase chain reaction analysis to determine the treatment effects on the gene expression of neuronal receptors associated with drug actions and ictogenesis. Our results indicated that single dose of VPA helps prevent the animals from getting convulsions, showing complete elimination of seizures, whereas 7 days of chronic VPA treatment had few effects in seizure behaviors. Acute CBD administration showed subtle attenuation of seizure behaviors, increasing seizure latency and decreasing the duration of the convulsion phase, but without entirely seizure abolition. Chronic CBD treatments had no significant effects on sound-induced seizures, although some animals slightly improved seizure severity. Acute and chronic CBD treatments have no significant adverse effects on body weight, hematological parameters, and liver function, although locomotor activity was reduced. The combination of VPA and CBD did not alter the therapeutic outcome of the VPA monotherapy, showing no apparent synergistic effects. As compared to sham animals, chronic treatments with CBD caused abnormal mRNA expression levels for Trpv1, Adora1, Slc29a1, and Cnr1 genes, whereas no differences in gene expression were found for Htr1a and Sigmar1. Our study shed light on the behavioral and molecular effects of CBD and VPA on the GASH/Sal model and constituted the basis to develop further studies on the pharmacological effects of CBD and its interactions with other anticonvulsants.

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Section: Introductionmentioning

confidence: 92%

Behavioral and Molecular Effects Induced by Cannabidiol and Valproate Administration in the GASH/Sal Model of Acute Audiogenic Seizures

Cabral-Pereira

Sánchez-Benito

Díaz-Rodríguez

et al. 2021

Front. Behav. Neurosci.

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“…All tissues harvested were put into storage at −80 • C until use. The RT-qPCR approach was identical to that used previously by our group (e.g., Damasceno et al, 2020;Sánchez-Benito et al, 2020). RNA from samples was extracted in accordance with the protocol of TRIzol TM Reagent (#15596026, Invitrogen).…”

Section: Quantitative Reverse Transcription Pcr (Rt-qpcr)mentioning

confidence: 99%

“…Brain tissue used for immunohistochemistry (3 control and 4 GASH/Sal hamsters) was processed in accordance with the routine protocols used in the laboratory (Sánchez-Benito et al, 2020). Briefly, after injection of a lethal dose of sodium pentobarbital (60 mg.kg −1 ) and the subsequent perfusion through the heart with 4% paraformaldehyde in 0.1 M phosphate buffer saline (PBS), brains were removed from the skull, cryoprotected by immersion in 30% sucrose, and coronal sections were cut with a freezing sliding microtome at 40 µm thickness.…”

Section: Brain Tissue Processing and Immunostainingmentioning

confidence: 99%

“…The CB1R was visualized following the indirect method of immunohistochemical staining described by Sánchez-Benito et al (2020). A primary polyclonal antibody anti-CB1R obtained in rabbit (CB1-Rb-Af380, Frontier Institute, Hokkaido, Japan) which binds to the C-terminal (NM007726) of the mouse protein CB1R was used since there was no primary antibody Anti-CB1R available specific for GASH/Sal hamster.…”

Section: Brain Tissue Processing and Immunostainingmentioning

confidence: 99%

“…To visualize the morphological features of immunostained cells, we used brain embedded in paraffin wax (2 control and 2 GASH/Sal hamsters) before cutting into coronal sections of 6 µm thickness, according to the protocols routinely used in our laboratory (Sánchez-Benito et al, 2020). Then, sections were mounted onto slides and followed the immunohistological staining procedure to visualize the CB1R protein at optical and confocal laser scanning microscopes.…”

Section: Brain Tissue Processing and Immunostainingmentioning

confidence: 99%

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Distribution of the Cannabinoid Receptor Type 1 in the Brain of the Genetically Audiogenic Seizure-Prone Hamster GASH/Sal

Fuerte-Hortigón

Gonçalves

et al. 2021

Front. Behav. Neurosci.

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The endocannabinoid system modulates epileptic seizures by regulating neuronal excitability. It has become clear that agonist activation of central type I cannabinoid receptors (CB1R) reduces epileptogenesis in pre-clinical animal models of epilepsy. The audiogenic seizure-prone hamster GASH/Sal is a reliable experimental model of generalized tonic-clonic seizures in response to intense sound stimulation. However, no studies hitherto had investigated CB1R in the GASH/Sal. Although the distribution of CB1R has been extensively studied in mammalian brains, their distribution in the Syrian golden hamster brain also remains unknown. The objective of this research is to determine by immunohistochemistry the differential distribution of CB1R in the brains of GASH/Sal animals under seizure-free conditions, by comparing the results with wild-type Syrian hamsters as controls. CB1R in the GASH/Sal showed a wide distribution in many nuclei of the central nervous system. These patterns of CB1R-immunolabeling are practically identical between the GASH/Sal model and control animals, varying in the intensity of immunostaining in certain regions, being slightly weaker in the GASH/Sal than in the control, mainly in brain regions associated with epileptic networks. The RT-qPCR analysis confirms these results. In summary, our study provides an anatomical basis for further investigating CB1R in acute and kindling audiogenic seizure protocols in the GASH/Sal model as well as exploring CB1R activation via exogenously administered cannabinoid compounds.

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Genetic models of audiogenic seizures: What they are and how cannabinoids and Cannabis-derived compounds can be used to alleviate their symptoms—An updated narrative

Lazarini-Lopes¹,

Servilha-Menezes²,

Silva-Júnior³

et al. 2023

Medicinal Usage of Cannabis and Cannabinoids

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Morphological and molecular correlates of altered hearing sensitivity in the genetically audiogenic seizure-prone hamster GASH/Sal

Cited by 11 publications

References 87 publications

Behavioral and Molecular Effects Induced by Cannabidiol and Valproate Administration in the GASH/Sal Model of Acute Audiogenic Seizures

Behavioral and Molecular Effects Induced by Cannabidiol and Valproate Administration in the GASH/Sal Model of Acute Audiogenic Seizures

Distribution of the Cannabinoid Receptor Type 1 in the Brain of the Genetically Audiogenic Seizure-Prone Hamster GASH/Sal

Genetic models of audiogenic seizures: What they are and how cannabinoids and Cannabis-derived compounds can be used to alleviate their symptoms—An updated narrative

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