Back to Search
Start Over
Exploring the Effect of Endoplasmic Reticulum Stress Inhibition by 4-Phenylbutyric Acid on AMPA-Induced Hippocampal Excitotoxicity in Rat Brain
- Source :
- Neurotoxicity Research. 35:83-91
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- Excessive stimulation of ionotropic glutamate receptor is associated with glutamate-mediated excitotoxicity, thereby causing oxidative imbalance and mitochondrial dysfunction, resulting in the excitotoxic death of neurons. Eminent role of endoplasmic reticulum under glutamate-induced excitotoxicity has been highlighted in numerous literatures which have been observed to trigger endoplasmic reticulum stress (ER stress) as well as regulating oxidative stress. However, combating ER stress in excitotoxic neurons can provide a novel approach to alleviate the mitochondrial dysfunctioning and ROS generation. Therefore, we propose to investigate the cross-communication of α-amino-3-hydroxy-5-methyl-4-isoxzole-propionate (AMPA) excitotoxicity-induced oxidative injury with ER stress by employing ER stress inhibitor-4-phenlybutyric acid (4-PBA). Male SD rats were divided into four groups viz sham group (group 1), AMPA (10 mM)-induced excitotoxic group (group 2), curative group of AMPA-induced excitotoxic animals given 4-PBA at a dose of 100 mg/kg body weight (group 3), and alone 4-PBA treatment group (100 mg/kg body weight) (group 4). Animals were sacrificed after 15 days of treatment, and hippocampi were analyzed for histopathological examination, ROS, inflammatory markers, mitochondrial dysfunction, and ER stress markers. AMPA-induced excitotoxicity exhibited a significant increase in the levels of ROS, upregulated ER stress markers, inflammation markers, and compromised mitochondrial functioning in the hippocampus. However, 4-PBA administration significantly curtailed the AMPA-induced excitotoxic insult. This study suggests that targeting ER stress with a chemical chaperone can provide a better therapeutic intervention for neurological disorders involving excitotoxicity, and thus, it opens a new avenue to screen chemical chaperones for the therapeutic modalities.
- Subjects :
- Male
X-Box Binding Protein 1
0301 basic medicine
Cardiolipins
Excitotoxicity
Antineoplastic Agents
Inflammation
AMPA receptor
Pharmacology
Toxicology
medicine.disease_cause
Hippocampus
Statistics, Nonparametric
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Excitatory Amino Acid Agonists
Animals
Medicine
RNA, Messenger
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Heat-Shock Proteins
Membrane Potential, Mitochondrial
Electron Transport Complex I
business.industry
General Neuroscience
Endoplasmic reticulum
Endoplasmic Reticulum Stress
Activating Transcription Factor 4
Phenylbutyrates
Mitochondria
Rats
030104 developmental biology
Gene Expression Regulation
Unfolded protein response
Ionotropic glutamate receptor
medicine.symptom
Chemical chaperone
Reactive Oxygen Species
business
030217 neurology & neurosurgery
Oxidative stress
Subjects
Details
- ISSN :
- 14763524 and 10298428
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Neurotoxicity Research
- Accession number :
- edsair.doi.dedup.....2f9d716242c9beec63ff9de8b7a60039