PP.34.14

Abstract

Objective: Brain is a target-organ of hypertension, which is one of the major causes of cognitive decline. However, the mechanisms which explain how hypertension alters cognition are still ill-defined. Surprisingly, while BDNF (brain derived neurotrophic factor) plays a key role in cognition, the effect of hypertension on cerebral BDNF has been poorly investigated. A few studies reported decreased BDNF levels in the hippocampus. The present study aimed to determine regional brain levels and cellular localization of BDNF in spontaneously hypertensive rats (SHR) as compared to age-matched Wistar Kyoto rats (WKY). Design and method: Experiments were performed on brains collected from 13-week-old SHR and WKY (n = 11). BDNF levels and localization were assessed in the cortex, striatum and hippocampus by western blotting and immunohistochemistry analysis, respectively. Cerebral endothelial nitric oxide synthase (eNOS) activity was estimated from the Phospho-eNOS to eNOS protein expression ratio (western blotting analysis). Systolic and diastolic blood pressures (BP) were measured using the tail-cuff method. Results: Systolic and diastolic BP (mm Hg) were higher in SHR (180 ± 8 and 150 ± 12, respectively) than in WKY (112 ± 3 and 92 ± 5, respectively). Hypertension led to decreased BDNF levels in the hippocampus (-33%, p = 0.011) while it increased the levels in the cortex (+67%, p = 0.006) and striatum (+77%, p = 0.005). BDNF expression in endothelial cells and cerebral eNOS activity were lower in SHR than WKY irrespective of the region considered. By contrast, the impact of hypertension on BDNF expression in neurons and astrocytes was region-dependent; neuronal BDNF expression was decreased in the hippocampus, increased in the striatum and not modified in the cortex while astrocytic expression was increased in the cortex and not changed elsewhere. Conclusions: Our results confirm decreased BDNF levels in the hippocampus in hypertension and identify endothelial-derived BDNF as a potential new actor in the pathophysiology of cognitive deficit associated to hypertension. Further studies are now required to assess the link between cerebral endothelial dysfunction and BDNF expression.