Analysis of expression profile of brain-derived neurotrophic factor and its receptors in central nervous system in spontaneously hypertensive rats

[Speaker] Kosuke Otani:1
[Co-author] Muneyoshi Okada:1, Hideyuki Yamawaki:1
1:Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan

Introduction: Systemic hypertension is a disease inducing heart disease, stroke and renal failure, which is mostly (~90 %) classified as essential hypertension (cause unknown). Spontaneously hypertensive rats (SHR) are animal model of human essential hypertension and develop hypertension at 7-15-week-old. Sympathetic nerve activity in vasomotor center of SHR increases. Several studies reported that expression pattern of brain-derived neurotrophic factor (BDNF) changes in central nervous system of SHR, suggesting that BDNF might be related to the pathology of high blood pressure in SHR. However, expression pattern of its receptor (TrkB and p75NTR) remains unknown. This study aimed to clarify it.
Methods: We dissected isolated brain from SHR and control Wistar Kyoto rats (WKY, 7-week-old) into five regions, including cerebral cortex (CC), cerebellum (CB), brainstem (BS), hypothalamus (HT) and hippocampus (HC). The mRNA and protein expression of BDNF, TrkB isoforms (FL, T1 and T2), p75NTR, GFAP used as an astrocyte marker and NeuN used as a neuronal marker was measured by real-time PCR and Western blotting.
Results: In SHR compared with WKY, BDNF mRNA significantly increased in CC and HT but decreased in BS, while BDNF (precursor and mature) protein did not change remarkably. TrkB FL mRNA in SHR significantly increased in CB and BS (<1.5 fold). TrkB T1 mRNA significantly increased in BS (<1.5 fold), while TrkB T2 mRNA did not change. TrkB FL and T1 protein in SHR did not change remarkably. p75NTR mRNA in SHR did not change remarkably, while p75NTR protein significantly increased in CB (<1.5 fold). GFAP protein in SHR significantly decreased in BS and HT. NeuN protein in SHR significantly increased in HC.
Discussion and conclusion: We for the first time revealed the detailed mRNA and protein expression profiles of BDNF and its receptors in brain regions of SHR. Augmentation of sympathetic nervous activity via central nervous system is one of the causes for development of hypertension. Further study may identify whether the altered quantity and quality of BDNF and its receptor are related to the central nervous control of pathogenesis of essential hypertension.

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