The potential role of age, region, and species differences in CD36 in neuroinflammation

Identification: Edler, Melissa



The potential role of age, region, and species differences in CD36 in neuroinflammation
Melissa K. Edler1, Cooper Johnson1, Jason R. Richardson1
1Northeast Ohio Medical University, Rootstown, OH
As a scavenger receptor that facilitates fatty acid and oxidized low-density lipoprotein uptake, cluster of differentiation 36 (CD36) has been implicated in cerebrovascular dysfunction, oxidative stress, and neuroinflammation in the brain. Yet no studies have examined the regional and cellular distribution of CD36 in the healthy brain. Here, we characterized CD36 gene and protein expression in the brains of young (3 months), middle-aged (14 months), and aged (19 and 26 months) C57BL/6J male mice and protein expression in adult male humans (24-44 years). Quantitative PCR in the frontal cortex, striatum, and hippocampus of mice revealed age and regional differences. Aged mice had decreased CD36 mRNA in the hippocampus relative to young mice. Regionally, young mice had 25 fold greater expression in the striatum compared to the frontal cortex, while aged mice had a 5 fold and 4 fold increase in the striatum relative to the frontal cortex and hippocampus (p's ≤ 0.03). CD36 protein expression also changed regionally with age and was primarily located in the microvasculature. Compared to young mice, middle-aged and aged mice displayed greater CD36 immunoreactivity in the primary motor, somatosensory, and parietal cortices as well as the CA1 and CA3 hippocampal subfields. The striatum and midbrain exhibited minimal expression in 3 month olds, but by 19 months, displayed strong CD36 expression. Interestingly, some of these regions accumulate amyloid-beta (Aβ) peptides in the form of plaques in Alzheimer's disease (AD) or in the brain's blood vessels in cerebral amyloid angiopathy (CAA). CD36 has been shown to bind to fibrillar Aβ, inducing neuroinflammation, and CD36 deficiency was associated with restored cerebrovascular function in an AD mouse model. Therefore, we performed a neuroinflammatory challenge with the herbicide paraquat (10 mg/kg once per week for 2 weeks). Young and aged treated mice demonstrated CD36 expression in microglia, the brain's primary immune cell, and microvasculature cells. Additionally, preliminary immunofluorescent staining in the adult human brain revealed the presence of CD36 in microglia and microvessels. This data suggests that distinctive age, region, and species expression of CD36 in the brain may be an important factor in CAA and AD.



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