Fig. 1.

Brain-derived neurotrophic factor (BDNF)-deficient mice exhibit an elevated heart rate, and intracerebroventricular administration of BDNF lowers heart rate. (a) Heart rate was measured at 30 min intervals during a 24 h period in six wild-type (WT) and six BDNF-haploinsufficient (BDNF+/−) mice. The inset graph shows the average heart rates during the dark and light periods. The heart rate of WT and BDNF+/− mice was significantly higher during the night compared with the day time (night vs. day, F(1,20) = 20.17, *p < 0.01). However, BDNF+/− mice had a significantly higher heart rate compared with WT mice during both dark and light periods (WT vs. KO F(1,20) = 4.45, p < 0.05), which was also indicated by the average for the dark and light period (p < 0.05) (b and c). A single intraventricular bolus infusion of BDNF results in a transient decrease in heart rate in WT (n = 12) and BDNF+/− (n = 12) mice. Heart rate changes following infusion of either phosphate-buffered saline (PBS) or BDNF at a dose of 2.5 µg in WT and BDNF-deficient mice. Heart rate change was calculated using the average pre-infusion heart rate as the basal heart rate for each mouse. The infusions were initiated in the late morning after recording the baseline heart rate. Values are the mean and SEM. A repeated three-way ANOVA analysis indicated a significant change in heart rate during the recorded period for all mice (Time, F(39) = 5.19, p < 0.01). There was no difference between WT and BDNF+/− mice in response to PBS infusion. However, BDNF infusion significantly reduced heart rate compared with PBS infusion (PBS vs. BDNF, F(1,20) = 12.15, p < 0.01; time × PBS/BDNF F(1,39) = 2.61, p < 0.01). BDNF+/− mice had a significantly greater response to BDNF infusion compared with WT mice (WT vs. BDNF+/−, F(1,20) = 5.15, p < 0.05). The larger reduction in heart rate in response to BDNF infusion in BDNF+/− mice was contributed by a significantly higher basal heart rate in BDNF+/− mice compared with WT mice. Values are the mean and SEM.