PUBLICATION
Concurrent endoplasmic reticulum stress and demyelination in DEHP-exposed zebrafish larvae at the early developmental stages
- Authors
- Jindal, G., Mangla, A., Javed, M., Saifi, M.A., Mazahir, I., Mudgal, P., Raisuddin, S.
- ID
- ZDB-PUB-251121-10
- Date
- 2025
- Source
- Comparative biochemistry and physiology. Toxicology & pharmacology : CBP : 110394110394 (Journal)
- Registered Authors
- Keywords
- Apoptosis, DEHP, ER stress, Neuroinflammation, Scototaxis assay
- MeSH Terms
-
- Animals
- Apoptosis/drug effects
- Brain/drug effects
- Brain/metabolism
- Demyelinating Diseases*/chemically induced
- Demyelinating Diseases*/metabolism
- Demyelinating Diseases*/pathology
- Diethylhexyl Phthalate*/toxicity
- Endoplasmic Reticulum Stress*/drug effects
- Larva/drug effects
- Larva/growth & development
- Larva/metabolism
- Spinal Cord/drug effects
- Spinal Cord/metabolism
- Water Pollutants, Chemical*/toxicity
- Zebrafish*/growth & development
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 41265544 Full text @ Comp. Biochem. Physiol. C Toxicol. Pharmacol.
Citation
Jindal, G., Mangla, A., Javed, M., Saifi, M.A., Mazahir, I., Mudgal, P., Raisuddin, S. (2025) Concurrent endoplasmic reticulum stress and demyelination in DEHP-exposed zebrafish larvae at the early developmental stages. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. :110394110394.
Abstract
Di-ethylhexyl phthalate (DEHP) is an endocrine disruptor with established neurotoxic as well as potential neurodegenerative effects. The myelin sheath plays a crucial role in maintaining the health of the nervous system, whereas demyelination contributes to the onset of brain diseases. This study investigated the effect of DEHP on neurological development with special reference to endoplasmic reticulum (ER) stress, inflammation, and concurrently with demyelination and cellular apoptotic development in zebrafish larvae. Results indicated that DEHP exposure can lead to demyelination through ER stress and inflammation, as evident from decreased expression of myelin basic protein (Mbp) in both the brain and spinal cord of zebrafish larvae analyzed through immunofluorescent assay. The mRNA expression of axon marker nfl significantly increased, while tuba1a was decreased with DEHP exposure. ER stress markers such as inositol-requiring enzyme 1 alpha (Ire1), activating transcription factor 4 (Atf4), binding immunoglobulin protein (Bip), phosphorylated e-IF2 alpha (p-eIF2α), CCAAT/enhancer-binding protein homologous protein (Chop), and inflammatory markers (nuclear factor kappa B subunit p65; Nf-κb p65), ionized calcium-binding adaptor molecule 1 (Iba1), and glial fibrillary acid protein (Gfap), were significantly upregulated on exposure to DEHP, analyzed by western blotting. Scototaxis, a behavioral assay, was also altered in DEHP-treated larvae. Oxidative stress markers like superoxide dismutase (SOD), catalase, and monoamine oxidase (MAO) were also elevated. Apoptotic cells were observed in DEHP-treated zebrafish larvae using acridine orange staining. Overall, the DEHP exposure to zebrafish larvae caused myelin sheath degeneration and axonal dysfunction due to the generation of ER stress and inflammation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping