Axonal transport rate decreased at the onset of optic neuritis in EAE mice

Lin, Tsen-Hsuan; Kim, Joong Hee; Pérez-Torres, Carlos J.; Chiang, Chia‐Wen; Trinkaus, Kathryn; Cross, Anne H.; Song, Sheng‐Kwei

doi:10.1016/j.neuroimage.2014.06.009

Cited by 38 publications

(35 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In rodents, most (~98%) RGC axons project contralaterally to the SC . A defective axonal transport was described in mice with EAE‐ON . In agreement, LPS‐induced ON provoked a “misconnection” between the retina and the SC, whereas melatonin prevented the deficit in the anterograde transport from the retina to its main synaptic target in rodents.…”

Section: Discussionmentioning

confidence: 64%

Neuroprotective effect of melatonin in experimental optic neuritis in rats

Aranda

Fleitas

Laurentiis

et al. 2016

Journal of Pineal Research

View full text Add to dashboard Cite

Optic neuritis (ON) is an inflammatory, demyelinating, and neurodegenerative condition of the optic nerve, which might induce permanent vision loss. Currently, there are no effective therapies for this disorder. We have developed an experimental model of primary ON in rats through a single microinjection of 4.5 μg of bacterial lipopolysaccharide (LPS) into the optic nerve. Since melatonin acts as a pleiotropic therapeutic agent in various neurodegenerative diseases, we analyzed the effect of melatonin on LPS-induced ON. For this purpose, LPS or vehicle were injected into the optic nerve from adult male Wistar rats. One group of animals received a subcutaneous pellet of 20 mg melatonin at 24 hr before vehicle or LPS injection, and another group was submitted to a sham procedure. Melatonin completely prevented the decrease in visual evoked potentials (VEPs), and pupil light reflex (PLR), and preserved anterograde transport of cholera toxin β-subunit from the retina to the superior colliculus. Moreover, melatonin prevented microglial reactivity (ED1-immunoreactivity, P < 0.01), astrocytosis (glial fibrillary acid protein-immunostaining, P < 0.05), demyelination (luxol fast blue staining, P < 0.01), and axon (toluidine blue staining, P < 0.01) and retinal ganglion cell (Brn3a-immunoreactivity, P < 0.01) loss, induced by LPS. Melatonin completely prevented the increase in nitric oxide synthase 2, cyclooxygenase-2 levels (Western blot) and TNFα levels, and partly prevented lipid peroxidation induced by experimental ON. When the pellet of melatonin was implanted at 4 days postinjection of LPS, it completely reversed the decrease in VEPs and PLR. These data suggest that melatonin could be a promising candidate for ON treatment.

show abstract

Section: Discussionmentioning

confidence: 64%

Neuroprotective effect of melatonin in experimental optic neuritis in rats

Aranda

Fleitas

Laurentiis

et al. 2016

Journal of Pineal Research

View full text Add to dashboard Cite

show abstract

“…Visual acuity, utilized to measure visual function in parallel to clinical signs, was assessed with the Virtual Optometry System (Optomotry, Cerebral Mechanics, Inc., Canada) as previously described [23]. In short, mice were presented with virtual rotating columns displayed on four LCD screens.…”

Section: Methodsmentioning

confidence: 99%

Diffusion MRI quantifies early axonal loss in the presence of nerve swelling

Lin

Chiang

Pérez-Torres

et al. 2017

J Neuroinflammation

Self Cite

View full text Add to dashboard Cite

BackgroundMagnetic resonance imaging markers have been widely used to detect and quantify white matter pathologies in multiple sclerosis. We have recently developed a diffusion basis spectrum imaging (DBSI) to distinguish and quantify co-existing axonal injury, demyelination, and inflammation in multiple sclerosis patients and animal models. It could serve as a longitudinal marker for axonal loss, a primary cause of permanent neurological impairments and disease progression.MethodsEight 10-week-old female C57BL/6 mice underwent optic nerve DBSI, followed by a week-long recuperation prior to active immunization for experimental autoimmune encephalomyelitis (EAE). Visual acuity of all mice was assessed daily. Longitudinal DBSI was performed in mouse optic nerves at baseline (naïve, before immunization), before, during, and after the onset of optic neuritis. Tissues were perfusion fixed after final in vivo scans. The correlation between DBSI detected pathologies and corresponding immunohistochemistry markers was quantitatively assessed.ResultsIn this cohort of EAE mice, monocular vision impairment occurred in all animals. In vivo DBSI detected, differentiated, and quantified optic nerve inflammation, demyelination, and axonal injury/loss, correlating nerve pathologies with visual acuity at different time points of acute optic neuritis. DBSI quantified, in the presence of optic nerve swelling, ~15% axonal loss at the onset of optic neuritis in EAE mice.ConclusionsOur findings support the notion that axonal loss could occur early in EAE mice. DBSI detected pathologies in the posterior visual pathway unreachable by optical coherence tomography and without confounding inflammation induced optic nerve swelling. DBSI could thus decipher the interrelationship among various pathological components and the role each plays in disease progression. Quantification of the rate of axonal loss could potentially serve as the biomarker to predict treatment outcome and to determine when progressive disease starts.

show abstract

“…As a calcium analog, Mn 2+ enters neurons via voltage-gated calcium channels (Drapeau and Nachshen, 1984;Narita et al, 1990;Sloot and Gramsbergen, 1994;Lu et al, 2007), where it travels within vesicles along microtubules by fast axonal transport (Merritt et al, 1989;Takeda et al, 1998;Silva et al, 2004;Smith et al, 2007;Zhang et al, 2010) in a process that is at least partially dependent on the motor protein kinesin (Bearer et al, 2007(Bearer et al, , 2009). Here we utilized MRI to visualize Mn 2+ enhancement of the optic nerve projections (see Lin et al, 2014) from the retina to the superior colliculus. From intravitreal injection, Mn 2+ has been shown to enter retinal ganglion cells and to travel within their axons in the anterograde direction along the optic nerve to the superior colliculus and lateral geniculate nucleus (Bearer et al, 2007;Watanabe et al, 2001).…”

Section: Introductionmentioning

confidence: 99%