Chronobiotic effect of melatonin in experimental optic neuritis. (January 2021)

• Record Type: Journal Article
• Authors: Aranda, Marcos L.; Narvaez, Omar; Altschuler, Florencia; Calanni, Juan S.; González Fleitas, María F.; Sande, Pablo H.; Dorfman, Damián; Concha, Luis; Rosenstein, Ruth E.
• Is Part Of: Neuropharmacology. Volume 182(2021)
• Publication Date: 2021-01
• Subjects: Optic neuritis -- Non-image forming visual system -- Melanopsin -- Pupil light reflex -- Locomotor activity -- Melatonin; CSD constrained spherical deconvolution -- CTB cholera toxin β-subunit -- DTI diffusion tensor imaging -- DWI diffusion weighted images -- EAE experimental autoimmune encephalomyelitis -- FA fractional anisotropy -- IFVS image-forming visual system -- ipRGCs intrinsically photosensitive retinal ganglion cells -- LGN lateral geniculate nucleus -- LPS bacterial lipopolysaccharide -- MS multiple sclerosis -- NIFVS non-image-forming visual system -- ON optic neuritis -- OPN olivary pretectal nucleus -- PLR pupil light reflex -- RGCs retinal ganglion cells -- SC superior colliculus -- SCN suprachiasmatic nucleus -- VEPs visual evoked potentials; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2020.108401
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Optic neuritis (ON) is an inflammatory condition of the optic nerve, which leads to retinal ganglion cell (RGC) loss. A subset of RGCs expressing the photopigment melanopsin regulates non-image-forming visual system (NIFVS) functions such as pupillary light reflex (PLR) and circadian rhythms. Melatonin is a chronobiotic agent able to regulate the circadian system. We analyzed the effect of ON on the NIFVS, and the effect of melatonin on the NIFVS alterations induced by ON. For this purpose, optic nerves from male Wistar rats received vehicle or bacterial lipopolysaccharide (LPS), and one group of animals received a subcutaneous pellet of melatonin or a sham procedure. The NIFVS was analyzed in terms of: i) blue light-evoked PLR, ii) the communication between the retina and the suprachiasmatic nuclei (by anterograde transport, and ex vivo magnetic resonance images), iii) locomotor activity rhythm, and iv) Brn3a(+) and melanopsin(+) RGC number (by immunohistochemistry). Experimental ON significantly decreased the blue light-evoked PLR, induced a misconnection between the retina and the suprachiasmatic nuclei, decreased Brn3a(+) RGCs, but not melanopsin(+) RGC number. A bilateral injection of LPS significantly increased the light (but not dark) phase locomotor activity, rhythm periodicity, and time of offset activity. Melatonin prevented the decrease in blue light-evoked PLR, and locomotor activity rhythm alterations induced by ON. These results support that ON provoked alterations of the circadian physiology, and that melatonin could restore the circadian system misalignment. Highlights: Optic neuritis leads to retinal ganglion cell loss and visual dysfunction. Melatonin is a chronobiotic agent able to regulate the circadian system. Optic neuritis alters the pupillary reflex and locomotor activity rhythm. Melatonin prevents optic neuritis-induced circadian alterations. Melatonin could restore the circadian system misalignment induced by optic neuritis.