Abstract P205: Age-dependent Alteration in Expression of Brain-derived Neurotrophic Factor and its Receptors in Central Nervous System of Spontaneously Hypertensive Rats.

Abstract

Background and Aim: Essential hypertension is a cause unknown disease leading to heart disease, stroke and renal failure. Spontaneously hypertensive rats (SHR) are animal model of human essential hypertension and develop hypertension at 7-15-week-old. Several studies reported expression pattern of brain-derived neurotrophic factor (BDNF) changes in central nervous system (CNS) in SHR, suggesting that BDNF and its receptors might be related to increased blood pressure. However, age-dependent change in BDNF and receptors (TrkB and p75NTR) remains to be elucidated. This study aimed to clarify it. Method: Isolated brain tissues from SHR and control Wistar Kyoto Rats (WKY) at 4-, 7- and 15-week-old were dissected into five regions (cerebral cortex: CC; cerebellum: CB; brainstem: BS; hypothalamus: HT; hippocampus: HC). Protein and mRNA expression of BDNF, TrkB isoforms (FL, T1 and T2) and p75NTR as well as an inflammatory marker NOX-2 was examined by Western blotting and real-time PCR. Results: The following data showed significant difference in SHR compared with WKY (n = 4): pro-BDNF protein was lower by 49.9% (4-week, p < 0.05) and 38.2% (7-week, p < 0.05) in HT, while mature BDNF protein was lower by 21.9% in HC (15-week, p < 0.05). TrkB FL mRNA was higher by 32.5% in CB (7-week, p < 0.05) and 43.1% in BS (7-week, p < 0.05), while TrkB FL protein was higher by 51.4% in BS (15-week, p < 0.05). TrkB T1 mRNA was higher by 22.8% in BS (7-week, p < 0.05) and 17.2% in HT (15-week, p < 0.05), while TrkB T1 protein was higher by 56.1% in BS (4-week, p < 0.01). p75NTR protein was higher by 46.9% in CB (7-week, p < 0.05). NOX-2 mRNA was higher by 29.1% (4-week, p < 0.01), 104.2% (7-week, p < 0.01) and 75.8% (15-week, p < 0.05) in CC, 27.0% in CB (15-week, p < 0.05), 34.6% in BS (4-week, p < 0.05), 326.1% in HT (15-week, p < 0.01) and 29.8% in HC (7-week, p < 0.05). Conclusion: We for the first time revealed age-dependent changes in expression of BDNF and its receptors in CNS of SHR. Specifically, our results suggest that alteration of BDNF and TrkB expression is already occurred at juvenile before a stable blood pressure increase. The upregulation of NOX-2 was also identified. Further detailed study might identify whether and how BDNF-receptor-oxidative stress axis is related to pathogenesis of essential hypertension.