Cargando…
Antiseizure Effects of Cannabidiol Leading to Increased Peroxisome Proliferator-Activated Receptor Gamma Levels in the Hippocampal CA3 Subfield of Epileptic Rats
We evaluated the effects of cannabidiol (CBD) on seizures and peroxisome proliferator-activated receptor gamma (PPARγ) levels in an animal model of temporal lobe epilepsy (TLE). Adult male Sprague-Dawley rats were continuously monitored by video-electrocorticography up to 10 weeks after an intraperi...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147091/ https://www.ncbi.nlm.nih.gov/pubmed/35631322 http://dx.doi.org/10.3390/ph15050495 |
_version_ | 1784716722948800512 |
---|---|
author | Costa, Anna-Maria Russo, Fabiana Senn, Lara Ibatici, Davide Cannazza, Giuseppe Biagini, Giuseppe |
author_facet | Costa, Anna-Maria Russo, Fabiana Senn, Lara Ibatici, Davide Cannazza, Giuseppe Biagini, Giuseppe |
author_sort | Costa, Anna-Maria |
collection | PubMed |
description | We evaluated the effects of cannabidiol (CBD) on seizures and peroxisome proliferator-activated receptor gamma (PPARγ) levels in an animal model of temporal lobe epilepsy (TLE). Adult male Sprague-Dawley rats were continuously monitored by video-electrocorticography up to 10 weeks after an intraperitoneal kainic acid (15 mg/kg) injection. Sixty-seven days after the induction of status epilepticus and the appearance of spontaneous recurrent seizures in all rats, CBD was dissolved in medium-chain triglyceride (MCT) oil and administered subcutaneously at 120 mg/kg (n = 10) or 12 mg/kg (n = 10), twice a day for three days. Similarly, the vehicle was administered to ten epileptic rats. Brain levels of PPARγ immunoreactivity were compared to those of six healthy controls. CBD at 120 mg/kg abolished the seizures in 50% of rats (p = 0.033 vs. pre-treatment, Fisher’s exact test) and reduced total seizure duration (p < 0.05, Tukey Test) and occurrence (p < 0.05). PPARγ levels increased with CBD in the hippocampal CA1 subfield and subiculum (p < 0.05 vs. controls, Holm–Šidák test), but only the highest dose increased the immunoreactivity in the hippocampal CA3 subfield (p < 0.001), perirhinal cortex, and amygdala (p < 0.05). Overall, these results suggest that the antiseizure effects of CBD are associated with upregulation of PPARγ in the hippocampal CA3 region. |
format | Online Article Text |
id | pubmed-9147091 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91470912022-05-29 Antiseizure Effects of Cannabidiol Leading to Increased Peroxisome Proliferator-Activated Receptor Gamma Levels in the Hippocampal CA3 Subfield of Epileptic Rats Costa, Anna-Maria Russo, Fabiana Senn, Lara Ibatici, Davide Cannazza, Giuseppe Biagini, Giuseppe Pharmaceuticals (Basel) Article We evaluated the effects of cannabidiol (CBD) on seizures and peroxisome proliferator-activated receptor gamma (PPARγ) levels in an animal model of temporal lobe epilepsy (TLE). Adult male Sprague-Dawley rats were continuously monitored by video-electrocorticography up to 10 weeks after an intraperitoneal kainic acid (15 mg/kg) injection. Sixty-seven days after the induction of status epilepticus and the appearance of spontaneous recurrent seizures in all rats, CBD was dissolved in medium-chain triglyceride (MCT) oil and administered subcutaneously at 120 mg/kg (n = 10) or 12 mg/kg (n = 10), twice a day for three days. Similarly, the vehicle was administered to ten epileptic rats. Brain levels of PPARγ immunoreactivity were compared to those of six healthy controls. CBD at 120 mg/kg abolished the seizures in 50% of rats (p = 0.033 vs. pre-treatment, Fisher’s exact test) and reduced total seizure duration (p < 0.05, Tukey Test) and occurrence (p < 0.05). PPARγ levels increased with CBD in the hippocampal CA1 subfield and subiculum (p < 0.05 vs. controls, Holm–Šidák test), but only the highest dose increased the immunoreactivity in the hippocampal CA3 subfield (p < 0.001), perirhinal cortex, and amygdala (p < 0.05). Overall, these results suggest that the antiseizure effects of CBD are associated with upregulation of PPARγ in the hippocampal CA3 region. MDPI 2022-04-19 /pmc/articles/PMC9147091/ /pubmed/35631322 http://dx.doi.org/10.3390/ph15050495 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Costa, Anna-Maria Russo, Fabiana Senn, Lara Ibatici, Davide Cannazza, Giuseppe Biagini, Giuseppe Antiseizure Effects of Cannabidiol Leading to Increased Peroxisome Proliferator-Activated Receptor Gamma Levels in the Hippocampal CA3 Subfield of Epileptic Rats |
title | Antiseizure Effects of Cannabidiol Leading to Increased Peroxisome Proliferator-Activated Receptor Gamma Levels in the Hippocampal CA3 Subfield of Epileptic Rats |
title_full | Antiseizure Effects of Cannabidiol Leading to Increased Peroxisome Proliferator-Activated Receptor Gamma Levels in the Hippocampal CA3 Subfield of Epileptic Rats |
title_fullStr | Antiseizure Effects of Cannabidiol Leading to Increased Peroxisome Proliferator-Activated Receptor Gamma Levels in the Hippocampal CA3 Subfield of Epileptic Rats |
title_full_unstemmed | Antiseizure Effects of Cannabidiol Leading to Increased Peroxisome Proliferator-Activated Receptor Gamma Levels in the Hippocampal CA3 Subfield of Epileptic Rats |
title_short | Antiseizure Effects of Cannabidiol Leading to Increased Peroxisome Proliferator-Activated Receptor Gamma Levels in the Hippocampal CA3 Subfield of Epileptic Rats |
title_sort | antiseizure effects of cannabidiol leading to increased peroxisome proliferator-activated receptor gamma levels in the hippocampal ca3 subfield of epileptic rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147091/ https://www.ncbi.nlm.nih.gov/pubmed/35631322 http://dx.doi.org/10.3390/ph15050495 |
work_keys_str_mv | AT costaannamaria antiseizureeffectsofcannabidiolleadingtoincreasedperoxisomeproliferatoractivatedreceptorgammalevelsinthehippocampalca3subfieldofepilepticrats AT russofabiana antiseizureeffectsofcannabidiolleadingtoincreasedperoxisomeproliferatoractivatedreceptorgammalevelsinthehippocampalca3subfieldofepilepticrats AT sennlara antiseizureeffectsofcannabidiolleadingtoincreasedperoxisomeproliferatoractivatedreceptorgammalevelsinthehippocampalca3subfieldofepilepticrats AT ibaticidavide antiseizureeffectsofcannabidiolleadingtoincreasedperoxisomeproliferatoractivatedreceptorgammalevelsinthehippocampalca3subfieldofepilepticrats AT cannazzagiuseppe antiseizureeffectsofcannabidiolleadingtoincreasedperoxisomeproliferatoractivatedreceptorgammalevelsinthehippocampalca3subfieldofepilepticrats AT biaginigiuseppe antiseizureeffectsofcannabidiolleadingtoincreasedperoxisomeproliferatoractivatedreceptorgammalevelsinthehippocampalca3subfieldofepilepticrats |