The GABAergic System and Endocannabinoids in Epilepsy and Seizures: What Can We Expect from Plant Oils?

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2022 Jun 10

PMID 35684543

Authors

Fabio Rodrigues de Oliveira

Nagila Monteiro da Silva

Moises Hamoy

Maria Elena Crespo-Lopez

Irlon Maciel Ferreira

Edilene Oliveira da Silva

Barbarella de Matos Macchi

Jose Luiz Martins do Nascimento

Affiliations

Soon will be listed here.

Abstract

Seizures and epilepsy are some of the most common serious neurological disorders, with approximately 80% of patients living in developing/underdeveloped countries. However, about one in three patients do not respond to currently available pharmacological treatments, indicating the need for research into new anticonvulsant drugs (ACDs). The GABAergic system is the main inhibitory system of the brain and has a central role in seizures and the screening of new ACD candidates. It has been demonstrated that the action of agents on endocannabinoid receptors modulates the balance between excitatory and inhibitory neurotransmitters; however, studies on the anticonvulsant properties of endocannabinoids from plant oils are relatively scarce. The Amazon region is an important source of plant oils that can be used for the synthesis of new fatty acid amides, which are compounds analogous to endocannabinoids. The synthesis of such compounds represents an important approach for the development of new anticonvulsant therapies.

Citing Articles

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References

Ravizza T, Boer K, Redeker S, Spliet W, van Rijen P, Troost D . The IL-1beta system in epilepsy-associated malformations of cortical development. Neurobiol Dis. 2006; 24(1):128-43. DOI: 10.1016/j.nbd.2006.06.003. View

Fezza F, Marrone M, Avvisati R, Di Tommaso M, Lanuti M, Rapino C . Distinct modulation of the endocannabinoid system upon kainic acid-induced in vivo seizures and in vitro epileptiform bursting. Mol Cell Neurosci. 2014; 62:1-9. DOI: 10.1016/j.mcn.2014.07.003. View

Shneker B, Fountain N . Assessment of acute morbidity and mortality in nonconvulsive status epilepticus. Neurology. 2003; 61(8):1066-73. DOI: 10.1212/01.wnl.0000082653.40257.0b. View

Garcia-Fernandez M . [Epileptic spasms in infants. Beyond hypsarrhythmia]. Rev Neurol. 2017; 64(s03):S55-S59. View

Kandratavicius L, Balista P, Lopes-Aguiar C, Ruggiero R, Umeoka E, Garcia-Cairasco N . Animal models of epilepsy: use and limitations. Neuropsychiatr Dis Treat. 2014; 10:1693-705. PMC: 4164293. DOI: 10.2147/NDT.S50371. View

Boonen J, Bronselaer A, Nielandt J, Veryser L, De Tre G, De Spiegeleer B . Alkamid database: Chemistry, occurrence and functionality of plant N-alkylamides. J Ethnopharmacol. 2012; 142(3):563-90. DOI: 10.1016/j.jep.2012.05.038. View

Battista N, Di Tommaso M, Bari M, Maccarrone M . The endocannabinoid system: an overview. Front Behav Neurosci. 2012; 6:9. PMC: 3303140. DOI: 10.3389/fnbeh.2012.00009. View

Marsicano G, Lutz B . Neuromodulatory functions of the endocannabinoid system. J Endocrinol Invest. 2006; 29(3 Suppl):27-46. View

Loscher W . Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure. 2011; 20(5):359-68. DOI: 10.1016/j.seizure.2011.01.003. View

10.

Cravatt B, Demarest K, Patricelli M, Bracey M, Giang D, Martin B . Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci U S A. 2001; 98(16):9371-6. PMC: 55427. DOI: 10.1073/pnas.161191698. View

11.

Jan Y, Jan L . Function of GB1 and GB2 subunits in G protein coupling of GABA(B) receptors. Proc Natl Acad Sci U S A. 2001; 98(25):14649-54. PMC: 64736. DOI: 10.1073/pnas.251554498. View

12.

Wang J, Ueda N . Role of the endocannabinoid system in metabolic control. Curr Opin Nephrol Hypertens. 2007; 17(1):1-10. DOI: 10.1097/MNH.0b013e3282f29071. View

13.

Wu C, Li C, Song H, Zhang H, Yang J, Wang Y . Selective effect of oleamide, an endogenous sleep-inducing lipid amide, on pentylenetetrazole-induced seizures in mice. J Pharm Pharmacol. 2003; 55(8):1159-62. DOI: 10.1211/0022357021431. View

14.

Savinainen J, Saario S, Laitinen J . The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2-arachidonoylglycerol signalling through cannabinoid receptors. Acta Physiol (Oxf). 2011; 204(2):267-76. PMC: 3320662. DOI: 10.1111/j.1748-1716.2011.02280.x. View

15.

Kubrusly R, Gunter A, Sampaio L, Martins R, Schitine C, Trindade P . Neuro-glial cannabinoid receptors modulate signaling in the embryonic avian retina. Neurochem Int. 2017; 112:27-37. DOI: 10.1016/j.neuint.2017.10.016. View

16.

Stafstrom C, Carmant L . Seizures and epilepsy: an overview for neuroscientists. Cold Spring Harb Perspect Med. 2015; 5(6). PMC: 4448698. DOI: 10.1101/cshperspect.a022426. View

17.

Oliveira F, Rodrigues K, Hamoy M, Sarquis I, Hamoy A, Lopez M . Fatty Acid Amides Synthesized from Andiroba Oil ( Aublet.) Exhibit Anticonvulsant Action with Modulation on GABA-A Receptor in Mice: A Putative Therapeutic Option. Pharmaceuticals (Basel). 2020; 13(3). PMC: 7151664. DOI: 10.3390/ph13030043. View

18.

Terlau J, Yang J, Khastkhodaei Z, Seidenbecher T, Luhmann H, Pape H . Spike-wave discharges in absence epilepsy: segregation of electrographic components reveals distinct pathways of seizure activity. J Physiol. 2020; 598(12):2397-2414. DOI: 10.1113/JP279483. View

19.

Katona I, Freund T . Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat Med. 2008; 14(9):923-30. DOI: 10.1038/nm.f.1869. View

20.

Loscher W . Animal Models of Seizures and Epilepsy: Past, Present, and Future Role for the Discovery of Antiseizure Drugs. Neurochem Res. 2017; 42(7):1873-1888. DOI: 10.1007/s11064-017-2222-z. View