PUBLICATION
Novel Zebrafish EAE model: A quick in vivo screen for multiple sclerosis
- Authors
- Kulkarni, P., Yellanki, S., Medishetti, R., Sriram, D., Saxena, U., Yogeeswari, P.
- ID
- ZDB-PUB-170121-8
- Date
- 2017
- Source
- Multiple sclerosis and related disorders 11: 32-39 (Journal)
- Registered Authors
- Kulkarni, Pushkar
- Keywords
- Drug Discovery, Experimental autoimmune encephalomyelitis (EAE), Fingolimod (Gilenya), Multiple Sclerosis (MS), Myelin oligodendrocyte glycoprotein (MOG), Zebrafish
- MeSH Terms
-
- Animals
- Dexamethasone/pharmacology
- Dimethyl Fumarate/pharmacology
- Drug Evaluation, Preclinical/methods*
- Encephalomyelitis, Autoimmune, Experimental/drug therapy*
- Encephalomyelitis, Autoimmune, Experimental/pathology
- Encephalomyelitis, Autoimmune, Experimental/physiopathology
- Fingolimod Hydrochloride/pharmacology
- Immunologic Factors/pharmacology
- Phenotype
- Sulfonamides/pharmacology
- Thiazoles/pharmacology
- Video Recording
- Zebrafish*
- PubMed
- 28104252 Full text @ Mult Scler Relat Disord
Citation
Kulkarni, P., Yellanki, S., Medishetti, R., Sriram, D., Saxena, U., Yogeeswari, P. (2017) Novel Zebrafish EAE model: A quick in vivo screen for multiple sclerosis. Multiple sclerosis and related disorders. 11:32-39.
Abstract
Introduction Pre-clinical drug discovery for multiple sclerosis (MS) is a labor intensive activity to perform in rodent models. This is owing to the long duration of disease induction and observation of treatment effects in an experimental autoimmune encephalomyelitis (EAE) model. We propose a novel adult zebrafish based model which offers a quick and simple protocol that can used to screen candidates as a step between in vitro experiments and rodent studies. The experiments conducted for this manuscript were to standardize a suitable model of EAE in adult zebrafish and validate it using known modulators.
Methods The EAE model was developed by disease induction with myelin oligodendrocyte glycoprotein - 35-55 (MOG) and observation of survival, clinical signs and body weight changes. We have validated this model using fingolimod. We have further performed detailed validation using dimethyl fumarate, dexamethasone and SR1001, which are known modulators of rodent EAE.
Results The immunization dose for the disease induction was observed to be 0.6mg/ml of MOG in CFA (Complete Freund's adjuvant), injected subcutaneously (s.c.) near spinal vertebrae. In the validation study with fingolimod, we have demonstrated the modulation of disease symptoms, which were also confirmed by histopathological evaluation. Furthermore, detailed validation with three other known drugs showed that our observations concur with those reported in conventional rodent models.
Discussion We have standardized and validated the adult zebrafish EAE model. This model can help get a quick idea of in vivo activity of drugs in a week using very low quantities of candidate compounds. Further work will be required to define this model particularly as it is found that zebrafish may not express a MOG homologue.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping