VDR activation ameliorates intermittent hypoxia-related cognitive impairment by upregulating TREM2 transcription

Neuroinflammation induced by intermittent hypoxia (IH) plays an essential role in the cognitive impairment associated with obstructive sleep apnea (OSA). It has been reported that the activation of Vitamin D receptor (VDR) can alleviate the neuroinflammation and neuronal injury in some neurodegenerative diseases However, it remains unknown whether VDR can play a similar role in OSA-related cognitive impairment and how it works. This study found that activating VDR by calcitriol enhanced the expression of triggering receptor on myeloid cells 2 (TREM2), promoted microglia M2 polarization, further mitigated neuroinflammation and neuronal damage induced by IH in mice and in BV2 cells. These improvements were attenuated in BV2 cells exposed to IH with calcitriol when TREM2 was knockdown. To determine how VDR regulated the expression of TREM2, potential binding sites between VDR and TREM2 promoter were identified in HEK293T cells. These results indicated that the activation of VDR could ameliorate IH-induced cognitive impairment by binding to TREM2 promoter region and promoting the transcription of TREM2. This study provides a potential therapeutic target for cognitive impairment in patients with OSA.