Hippocampal expression and distribution of CB1 receptors in the Amazonian rodent Proechimys: An animal model of resistance to epilepsy

Abstract

Proechimys, a rodent living in the Amazon region, has shown resistance to developing chronic epilepsy when submitted to different experimental models. Recently, many studies have attributed a potent anticonvulsant action to cannabinoid receptor CB1. This study investigated the distribution and expression of the CB1 receptor in the hippocampal formation of Proechimys using immunohistochemistry and Western blotting techniques. Results were compared with values obtained from adult Wistar rats. The immunoreactivity for CB1 was evident throughout the Ammon's horn and in the hilar region of both animal species. However, the distribution of these receptors was higher in the stratum lucidum of CA3 and in the hilar region of Proechimys. In addition, higher expression of CB1 receptors was observed in the Proechimys hippocampus. These data could explain, at least partially, the natural resistance of this animal species to developing spontaneous seizures following epileptogenic precipitating events.

Statistical parametric mapping reveals regional alterations in cannabinoid CB1 receptor distribution and G‐protein activation in the 3D reconstructed epileptic rat brain

“…However, recent studies in the mouse pilocarpine model have found that CB 1 receptors increase on glutamatergic and GABAergic synapses (Karlocai et al, 2011); therefore, the nature of these changes has yet to be fully elucidated. Nonetheless, the cannabinoid system has been implicated in the hippocampus in several other seizure models (Chen et al, 2003(Chen et al, , 2007Araujo et al, 2010), and potential clinical relevance has been corroborated with findings that changes in the endocannabinoid system occur in the hippocampus of patients with epilepsy (Ludanyi et al, 2008;Romigi et al, 2010).…”

Endocannabinoids and diacylglycerol kinase activity

“…Pharmacological studies have shown that it is the type 1 cannabanoid receptor that is linked to epileptic events [20]. The natural resistance of certain species to epileptic seizures has been suggested to be a consequence of their high level of expression of type 1 cannabanoid receptors [21]. The formation of 2-AG resulting in the activation of type 1 cannabanoid receptors will be affected by the activity of DGKε that reduces the fraction of SAG converted to 2-AG.…”

Equipotent Inhibition of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase – Dual Targets of the Endocannabinoid System to Protect against Seizure Pathology

“…Related to this response to injury, FAAH inhibition enhanced the salutary effects of cannabinergic signaling in the rat hippocampus, mediated predominantly via CB1 receptors [1,14,34,35]. It has been suggested that CB1 receptor activation reduces excessive glutamatergic signaling and excitotoxic progression thereby protecting hippocampal cells from cytoskeletal and synaptic damage [13,14,32,33,36]. These findings suggest a key role of endocannabinoids in attenuating excitotoxicity in the brain.…”