TY - JOUR
T1 - Behavioral and Molecular Responses to Exogenous Cannabinoids During Pentylenetetrazol-Induced Convulsions in Male and Female Rats
AU - Zirotti Rosenberg, Antonella
AU - Méndez-Ruette, Maxs
AU - Gorziglia, Mario
AU - Alzerreca, Benjamín
AU - Cabello, Javiera
AU - Kaufmann, Sofía
AU - Rambousek, Lukas
AU - Iturriaga Jofré, Andrés
AU - Wyneken, Ursula
AU - Lafourcade, Carlos A.
N1 - Publisher Copyright:
Copyright © 2022 Zirotti Rosenberg, Méndez-Ruette, Gorziglia, Alzerreca, Cabello, Kaufmann, Rambousek, Iturriaga Jofré, Wyneken and Lafourcade.
PY - 2022/8/9
Y1 - 2022/8/9
N2 - Epilepsy is a disabling, chronic brain disease,affecting ~1% of the World’s population, characterized by recurrent seizures (sudden, uncontrolled brain activity), which may manifest with motor symptoms (e.g., convulsions) or non-motor symptoms. Temporal lobe epilepsies (TLE) compromising the hippocampus are the most common form of focal epilepsies. Resistance in ~1/3 of epileptic patients to the first line of treatment, i.e., antiepileptic drugs (AEDs), has been an important motivation to seek alternative treatments. Among these, the plant Cannabis sativa (commonly known as marihuana) or compounds extracted from it (cannabinoids) have gained widespread popularity. Moreover, sex differences have been proposed in epilepsy syndromes and in cannabinoid action. In the hippocampus, cannabinoids interact with the CB1R receptor whose membrane levels are regulated by β-Arrestin2, a protein that promotes its endocytosis and causes its downregulation. In this article, we evaluate the modulatory role of WIN 55,212-2 (WIN), a synthetic exogenous cannabinoid on behavioral convulsions and on the levels of CB1R and β-Arrestin2 in female and male adolescent rats after a single injection of the proconvulsant pentylenetetrazol (PTZ). As epilepsies can have a considerable impact on synaptic proteins that regulate neuronal toxicity, plasticity, and cognition, we also measured the levels of key proteins markers of excitatory synapses, in order to examine whether exogenous cannabinoids may prevent such pathologic changes after acute seizures. We found that the exogenous administration of WIN prevented convulsions of medium severity in females and males and increased the levels of phosphorylated CaMKII in the hippocampus. Furthermore, we observed a higher degree of colocalization between CB1R and β-Arrestin2 in the granule cell layer.
AB - Epilepsy is a disabling, chronic brain disease,affecting ~1% of the World’s population, characterized by recurrent seizures (sudden, uncontrolled brain activity), which may manifest with motor symptoms (e.g., convulsions) or non-motor symptoms. Temporal lobe epilepsies (TLE) compromising the hippocampus are the most common form of focal epilepsies. Resistance in ~1/3 of epileptic patients to the first line of treatment, i.e., antiepileptic drugs (AEDs), has been an important motivation to seek alternative treatments. Among these, the plant Cannabis sativa (commonly known as marihuana) or compounds extracted from it (cannabinoids) have gained widespread popularity. Moreover, sex differences have been proposed in epilepsy syndromes and in cannabinoid action. In the hippocampus, cannabinoids interact with the CB1R receptor whose membrane levels are regulated by β-Arrestin2, a protein that promotes its endocytosis and causes its downregulation. In this article, we evaluate the modulatory role of WIN 55,212-2 (WIN), a synthetic exogenous cannabinoid on behavioral convulsions and on the levels of CB1R and β-Arrestin2 in female and male adolescent rats after a single injection of the proconvulsant pentylenetetrazol (PTZ). As epilepsies can have a considerable impact on synaptic proteins that regulate neuronal toxicity, plasticity, and cognition, we also measured the levels of key proteins markers of excitatory synapses, in order to examine whether exogenous cannabinoids may prevent such pathologic changes after acute seizures. We found that the exogenous administration of WIN prevented convulsions of medium severity in females and males and increased the levels of phosphorylated CaMKII in the hippocampus. Furthermore, we observed a higher degree of colocalization between CB1R and β-Arrestin2 in the granule cell layer.
KW - beta arrestin-2
KW - cannabinoids
KW - dentate gyrus
KW - epilepsy
KW - hippocampus
KW - seizures
UR - http://www.scopus.com/inward/record.url?scp=85136584035&partnerID=8YFLogxK
U2 - 10.3389/fnmol.2022.868583
DO - 10.3389/fnmol.2022.868583
M3 - Article
C2 - 36147210
AN - SCOPUS:85136584035
SN - 1662-5099
VL - 15
SP - 868583
JO - Frontiers in Molecular Neuroscience
JF - Frontiers in Molecular Neuroscience
M1 - 868583
ER -