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

Alejando Fuerte-Hortigón,Jaime Gonçalves,Ricardo Gómez-Nieto,Dolores E López,Laura Zeballos,Rubén Masa

doi:10.3389/fnbeh.2021.613798

Abstract

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.

Highlights

The endocannabinoid system consists of specific cannabinoid receptors, their endogenous ligands and the enzymatic systems of their biosynthesis and degradation (Svízenská et al, 2008)
We found strong and intense CB1R-immunolabeling in the following brain areas: cerebellum, substantia nigra, motor cortex, hippocampus, endopiriform nucleus, subtalamic nuclei, globus pallidus and olfactory bulb
We showed the immunohistochemical and gene expression analysis of the GASH/Sal model, comparing it with control hamsters and with what has already been described in the literature

Summary

Introduction

The endocannabinoid system consists of specific cannabinoid receptors, their endogenous ligands and the enzymatic systems of their biosynthesis and degradation (Svízenská et al, 2008). Endocannabinoids inhibit retrograde release of some neurotransmitters such as γ-aminobutyric acid, glutamate and serotonin (Pazos et al, 2005), since they regulate the aperture/closing of ion channels (Childers and Breivogel, 1998; Qian et al, 2017) in both excitatory (glutamatergic) and inhibitory (GABAergic) synapses (Julian et al, 2003), in response to an increase in the intracellular Ca2+ concentration (Ohno-Shosaku and Kano, 2014; Kendall and Yudowski, 2016) These regulatory effects are primarily mediated by two G-protein-coupled receptors: cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 (CB2R) (Marcu and Schechter, 2016; Lu and Potter, 2017). CB1Rs are highly expressed in brain areas responsible for mood regulation, motor co-ordination, cognition and pain such as the hippocampus, olfactory regions, caudate putamen, accumbens nucleus, substantia nigra, globus pallidus, periaqueductal gray matter, dorsal horn of the medulla, cingulate gyrus, neocortex, amygdala, hypothalamus, and solitary nucleus (Tsou et al, 1998; Svízenská et al, 2008; Hu and Mackie, 2015)

Methods

Results

Discussion

Conclusion