Related Experiment Video
Updated: Aug 7, 2026
Experimental Demyelination and Remyelination of Murine Spinal Cord by Focal Injection of Lysolecithin
Published on: March 26, 2015
RXR agonist, 9-cis-13,14-dihydroretinoic acid (9CDHRA), reduces damage and protects from demyelination in
Gabriella E Parrilla1, Roshana Vander Wall1, Nitin Chitranshi1
1Department of Clinical Medicine, Faculty of Medicine, Health and Human Sciences, Macquarie University, Wallumattagal Campus, 75 Talavera Road, Macquarie Park, NSW 2109, Australia.
Abstract:
Neurodegenerative and demyelinating disease, such as multiple sclerosis (MS) are at the forefront of medical research and the discovery of new drugs and therapeutics. One phenomenon of degeneration seen in these diseases is transsynaptic degeneration (TSD), where damage from one axon spreads to the other axons that are connected to it synaptically. It has previously been found that demyelination occurs prior to neuronal loss in an experimental form of induced TSD. Retinoid-x receptor (RXR) agonists have been shown to promote remyelination. Therefore, this study aimed to reveal the effects of a novel endogenous RXR-γ agonist, 9-cis-13,14-dihydroretinoic acid (9CDHRA), on preventing or restoring the effects of TSD. 9CDHRA was administered to mice following optic nerve crush (ONC) procedures, and electrophysiology (visual evoked potential, VEP) and histological (immunofluorescent) assessments were performed. It was found that 9CDHRA treatment effectively delayed glial activation and reduced the presence of apoptosis at the site of injury and further anterogradely in the visual system, including the lateral geniculate nucleus (LGN) and primary visual cortex (V1). Most notably, 9CDHRA was able to maintain myelin levels following ONC, and effectively protected from demyelination. This was corroborated by VEP recordings with improved P1 latency. The promising findings regarding the injury attenuating and myelin protecting properties of 9CDHRA necessitates further investigations into the potential therapeutic uses of this compound.
Insights
A novel compound, 9-cis-13,14-dihydroretinoic acid (9CDHRA), protected against demyelination and neuronal loss in a mouse model of transsynaptic degeneration (TSD). This offers potential for treating neurodegenerative diseases like multiple sclerosis (MS).
Area of Science:
- Neuroscience
- Pharmacology
- Ophthalmology
Background:
- Transsynaptic degeneration (TSD) is a key process in neurodegenerative diseases like multiple sclerosis (MS).
- Demyelination precedes neuronal loss in experimental TSD.
- Retinoid-X-receptor (RXR) agonists show potential for promoting remyelination.
Purpose of the Study:
- To investigate the therapeutic potential of 9-cis-13,14-dihydroretinoic acid (9CDHRA), an endogenous RXR-γ agonist, in preventing or restoring TSD effects.
- To evaluate 9CDHRA's impact on demyelination and neuronal survival following optic nerve crush (ONC).
Main Methods:
- Administration of 9CDHRA to mice after optic nerve crush (ONC).
- Electrophysiological assessment using visual evoked potential (VEP).
- Histological analysis including immunofluorescence staining.
Main Results:
- 9CDHRA treatment delayed glial activation and reduced apoptosis in the visual system.
- 9CDHRA effectively maintained myelin levels and prevented demyelination post-ONC.
- VEP recordings showed improved P1 latency, indicating functional protection.
Conclusions:
- 9CDHRA demonstrates significant injury-attenuating and myelin-protecting properties in a TSD model.
- The findings support further investigation of 9CDHRA as a therapeutic agent for neurodegenerative and demyelinating conditions.
- 9CDHRA shows promise in preserving visual system integrity following injury.
