Brain BDNF Levels Elevation Induced by Physical Training is Reduced after Unilateral Common Carotid Artery Occlusion in Rats

Abstract

We investigated the contribution of blood flow elevation in the cerebrovasculature to physical training-induced brain-derived neurotrophic factor (BDNF) levels elevation in the brain. Brain-derived neurotrophic factor protein levels were measured in the motor cortex 24 h after the last session of a forced treadmill walking (30 minutes a day, 18 m/minute for 7 consecutive days). Unilateral common carotid artery occlusion and modulation of exercise intensity (0 versus À 10% inclination of the treadmill) were used as strategies to reduce the (normal) elevation of flow in the cerebrovasculature occurring during exercise. Administration of N-nitro-L-arginine methyl ester (L-NAME, 60 mg/kg before each exercise sessions) and genetic hypertension (spontaneously hypertensive rats) were used as approaches to reduce stimulation of nitric oxide production in response to shear stress elevation. Vascular occlusion totally and partially abolished the effect of physical training on BDNF levels in the hemisphere ipsilateral and contralateral to occlusion, respectively. BDNF levels were higher after high than low exercise intensity. In addition, both genetic hypertension and L-NAME treatment blunted the effects of physical training on BDNF. From these results, we propose that elevation of brain BDNF levels elicited by physical training involves changes in cerebral hemodynamics.

Brain‐derived neurotrophic factor of the cerebral microvasculature: a forgotten and nitric oxide‐dependent contributor of brain‐derived neurotrophic factor in the brain

“…, Banoujaafar et al . ) and the hippocampus (unpublished results) were reported by our laboratory to be higher in exercised than sedentary rats. These data combined with the present results indicate that changes in cerebrovascular BDNF translate into parallel changes in brain BDNF levels, indicating that BDNF produced by the cerebral microvessels ends up in the brain, at least for a large part.…”

“…, Banoujaafar et al . ). It is noteworthy that our laboratory previously reported that the modalities of physical exercise and hypertension used in the present study respectively, increased and decreased BDNF levels in the heart and aorta (Prigent‐Tessier et al .…”

“…Furthermore, blood flow increases in many vascular beds, including vessels of the cerebral circulation during each exercise bout (Ogoh & Ainslie 2009, Sato et al 2011. We used an exercise programme that was previously reported by our laboratory to not change cardiovascular parameters (SBP, DBP and HR) (Prigent-Tessier et al 2013) but double BDNF levels in both the cortex (Quirie et al 2012, Banoujaafar et al 2014) and the aorta (Prigent-Tessier et al 2013). Thus, rats in the exercised group (EX) spent 30 min a day for seven consecutive days on a motor-driven horizontal treadmill with a speed fixed at 18 m min À1 .…”

Brain BDNF levels are dependent on cerebrovascular endothelium‐derived nitric oxide

“…EX consisted of a daily (30 min) walking activity (18 m/min) on a horizontal treadmill (model Exer-3/6; Linton Instrumentation, Norfolk, UK) for 7 consecutive days. We previously reported that this modality of EX resulted in a two-fold elevation in BDNF levels in the cortex (Quirie et al, 2012;Banoujaafar et al, 2014). Corresponding sedentary rats (SED) were kept in their cage in the vicinity of the treadmill.…”

“…Supporting a connection between brain BDNF levels and endothelium‐derived NO, the stroke‐induced rise in brain BDNF levels was reported to be lower in eNOS knock‐out animals than in wild‐type littermates (Chen et al ., ; Cui et al ., ). Likewise, pharmacological inhibition of NO synthases was shown to blunt the physical exercise‐induced elevation of brain BDNF levels (Chen et al ., ; Banoujaafar et al ., ). However, in the above studies, the presence of hypertension and the appearance of compensatory mechanisms in eNOS knock‐out mice (Ortiz & Garvin, ) as well as the use of a non‐selective NOS inhibitor complicated the interpretation of data.…”