Retinal ganglion cell loss and gliosis in the retinofugal projection following intravitreal exposure to amyloid-beta.
Inflammation; Glaucoma; Alzheimer's disease; Retina; Superior colliculus; Amyloid-beta; CD36; Cluster of differentiation 36
Pathological accumulations of amyloid-beta (Aβ) peptide are found in retina early in Alzheimer's disease, yet its effects on retinal neuronal structure remain unknown. To investigate this, we injected fibrillized Aβ(1-42) protein into the eye of adult C57BL/6 J mice and analyzed the retina, optic nerve (ON), and the superior colliculus (SC), the primary retinal target in mice. We found that retinal Aβ exposure stimulated microglial activation and retinal ganglion cell (RGC) loss as early as 1-week post-injection. Pathology was not limited to the retina, but propagated into other areas of the central nervous system. Microgliosis spread throughout the retinal projection (retina, ON, and SC), with multiplex protein quantitation demonstrating an increase in endogenously produced Aβ in the ON and SC corresponding to the injected retinas. Surprisingly, this pathology spread to the opposite side, with unilateral Aβ eye injections driving increased Aβ levels, neuroinflammation, and RGC death in the opposite, un-injected retinal projection. As Aβ-mediated microglial activation has been shown to propagate Aβ pathology, we also investigated the role of the Aβ-binding microglial scavenger receptor CD36 in this pathology. Transgenic mice lacking the CD36 receptor were resistant to Aβ-induced inflammation and RGC death up to 2 weeks following exposure. These results indicate that Aβ pathology drives regional neuropathology in the retina and does not remain isolated to the affected eye, but spreads throughout the nervous system. Further, CD36 may serve as a promising target to prevent Aβ-mediated inflammatory damage.
Simons ES;Smith M A;Dengler-Crish C M;Crish SD
Neurobiology of Disease
2020
2020-10-26
journalArticle
<a href="http://doi.org/10.1016/j.nbd.2020.105146" target="_blank" rel="noreferrer noopener">10.1016/j.nbd.2020.105146</a>
Age, sex, and regional differences in scavenger receptor CD36 in the mouse brain: Potential relevance to cerebral amyloid angiopathy and Alzheimer's disease.
brain; aging; mouse; Alzheimer's disease; cerebral amyloid angiopathy; vasculature; CD36; Alzheimer' s disease
Scavenger receptor CD36 contributes significantly to lipid homeostasis, inflammation, and amyloid deposition, while CD36 deficiency is associated with restored cerebrovascular function in an Alzheimer's disease (AD) mouse model. Yet the distribution of CD36 has not been examined in the brain. Here, we characterized CD36 gene and protein expression in the brains of young, middle aged, aged, and elderly male and female C57BL/6J mice. Age-related increases in CD36 mRNA expression were observed in the male hippocampus and female midbrain. Additionally, male mice had greater CD36 mRNA expression than females in the striatum, hippocampus, and midbrain. CD36 protein was primarily expressed intravascularly, and this expression differed by region, age, and sex in the mouse brain. Although male mice brains demonstrated an increase in CD36 protein with age in several cortices, basal ganglia, hippocampus, and midbrain, a decrease with age was observed in female mice in the same regions. These data suggest that distinctive age, region, and sex expression of CD36 in the brain may contribute to Aβ deposition and neuroinflammation in AD.
Edler MK; Johnson CT; Ahmed HS; Richardson JR
The Journal of Comparative Neurology
2020
2020-12-14
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1002/cne.25089" target="_blank" rel="noreferrer noopener">10.1002/cne.25089</a>