Background- Astrocytes contribute to neuroinflammation that accompanies neurodegenerative disorders such as Alzheimer’s disease (AD). In this sense, the toxicity of these diseases might be attenuated through the modulation of astrocytic inflammatory responses. Recently, the CD300f immunoreceptor was described as a new member of the CD300 immunoreceptor family, showing promising modulatory properties. Objective- Here, we investigated whether overexpression of hCD300f (the human isoform of CD300f) in astrocytes protects hippocampal neurons against the degeneration induced by amyloid-beta (Aβ) oligomer. Method- Astrocyte monolayers were transfected with hCD300f before seeding the hippocampal neurons, and then the co-culture was exposed to Aβ1-42 oligomers (5 μM, 48h). Results- hCD300f expression significantly abrogated the neuronal loss elicited by Aβ. This effect was dependent on neuron-astrocyte cell-cell interactions since no protection was observed using conditioned media from transfected astrocytes. Astrocyte modulation was dependent on the cytoplasmic signaling tail of hCD300f. Furthermore hCD300f expression did not affect the ability of astrocytes to uptake Aβ142 oligomers by endocytosis, which discards the possibility that increased Aβ1-42 clearance could mediate neuroprotection by hCD300f. Conclusion- These results suggest that the astrocyte-directed expression of the hCD300f immune receptor can be a neuroprotective strategy in AD disease.
