Evaluation of HIF-1 Involvement in the BDNF and ProBDNF Signaling Pathways among Obstructive Sleep Apnea Patients

Abstract

Obstructive Sleep Apnea (OSA) is a chronic condition characterized by intermittent hypoxia associated with multiple comorbidities, including psychiatric disorders, such as depression, insomnia, and cognitive impairment. The brain-derived neurotrophic factor (BDNF) and proBDNF singling pathways have been shown to be involved in this group of diseases. Furthermore, their expression might be affected by hypoxia-inducible factor 1 (HIF-1), which is an oxygen sensitive transcription factor due to its alpha subunit. Therefore, this study aimed to evaluate the association between HIF-1α, BDNF, and proBDNF protein levels among OSA patients. This study included 40 individuals who underwent polysomnography (PSG) and were divided into the OSA group (n = 20; AHI ≥ 30) and healthy control (n = 20; AHI < 5) based on the apnea−hypopnea index (AHI). All participants had their peripheral blood collected in the evening before and the morning after the PSG. BDNF, proBDNF, and HIF-1α protein concertation measurements were performed using ELISA. No differences were found in BDNF, proBDNF, and HIF-1α protein levels between OSA and the control group, both in the evening and in the morning. In the OSA group, i.e., the linear regression model, the morning BDNF protein level was predicted by age (ß = −0.389, p = 0.023) and the mean SpO2 of desaturations during sleep (ß = −0.577, p = 0.002). This model accounted for 63.3% of the variability in the morning BDNF protein level (F = 14.639, p < 0.001). The morning proBDNF protein level was predicted by age (ß = −0.395, p = 0.033) and HIF-1α morning protein level (ß = −3.192, p = 0.005). This model accounted for 52.4% of the variability in the morning BDNF protein level (F = 9.355, p = 0.002). The obtained results suggest that the HIF-1 transcription factor might be involved in the pathway activated by proBDNF, which may have protective properties from hypoxia in OSA patients.

Keywords: OSA; PSG; hypoxia; neurotrophin; oxygen saturation.

Figure 1

Correlation between morning BDNF and proBDNF protein levels and the chosen variables in the OSA group. Abbreviations: BDNF—brain-derived neurotrophic factor, HIF-1—hypoxia-inducible factor 1, OSA—obstructive sleep apnea, SpO₂—oxygen saturation. (A) Correlation between the BDNF protein level in the morning and age; (B) correlation between the BDNF protein level in the morning and total sleep time (TST); (C) correlation between the BDNF protein level in the morning and HIF-1 alpha protein level in the morning; (D) correlation between the BDNF protein level in the morning and Basal SpO₂ level; (E) correlation between the BDNF protein level in the morning and mean SpO₂ of desaturations during sleep; (F) correlation between the proBDNF protein level in the morning and age; (G) correlation between the proBDNF protein level in the morning and total sleep time (TST); (H) correlation between the proBDNF protein level in the morning and HIF-1 alpha protein level in the morning; (I) correlation between the proBDNF protein level in the morning and Basal SpO₂ level; (J) correlation between the proBDNF protein level in the morning and mean SpO₂ of desaturations during sleep.