Article Figures & Data
Figures
- Figure 1.
Hyperpolarized 13C-pyruvate magnetic resonance spectroscopic imaging reveals a decline in lactate following DCA administration. A, Injection and imaging regime of 9-month-old mice using hyperpolarized MRSI of [1-13C] pyruvate to measure the conversion of pyruvate to lactate. Mice were imaged after the first 13C-pyruvate injection (Before) and 30 min later were then injected with DCA (200 mg/kg). Following a 30 min recovery time, another injection of 13C-pyruvate and imaging were performed (After). B, 1H MRI of the brain in the coronal field overlayed with MRSI voxels containing spectra of 13C-labeled pyruvate and lactate (yellow). C, Conversion of pyruvate to lactate was measured as a ratio of the observed lactate peak to pyruvate peak from before DCA injection (blue line) and after (red dashed line). A pyruvate hydrate peak was also recorded. D, DCA injection reduces the ratio of lactate to pyruvate in the mouse brain (p = 0.04). Data shown are the mean ± SEM. n = 4.
- Figure 2.
DCA injection reduces the phosphorylation of PDH in the frontal cortex and hippocampus. A, B, Western blot analysis (left) was performed on extracts from the frontal cortex (A) and the hippocampus (B) of mice intraperitoneally injected with either saline or DCA (200 mg/kg) 30 min before being killed. Densitometric analysis of Western blots (right) revealed significantly lower PDH phosphorylation in DCA-treated mice relative to saline-injected mice (*p < 0.05, ***p < 0.001; n = 6 and 6, respectively, for extracts from the frontal cortex of saline- and DCA-injected mice; and n = 7 and 7, respectively, for extracts from the hippocampus of saline- and DCA-injected mice). Band densities were standardized to β-actin controls. Data shown are the mean ± SEM.
- Figure 3.
DCA administration causes impairment in spatial learning. Mice were intraperitoneally injected with saline or DCA (200 mg/kg) 30 min before each day of training and allowed to find the location of a hidden platform in the northwest quadrant. A–C, The latency to find the platform (A), the total path length (B), and the mean speed (C) were recorded on each training day. D–G, On day 5, a probe trial was performed without DCA injection, and mice were allowed to swim for 60 s. D, The swim path for each group of mice was compiled into heat map representations. E–G, Measurements were taken for the total distance traveled (E), the percentage of time spent in the correct quadrant (F), and the number of times the boundary of the platform was crossed (G). H, A week after the first probe trial, mice were again tested with a second probe trial, and measurements were taken for the number of times the boundary of the platform was crossed. Data shown are the mean ± SEM. *p < 0.05, **p < 0.01. n = 7 and 7 for saline and DCA treatments, respectively.
- Figure 4.
DCA administration does not interfere with memory retrieval. MWM performed by mice intraperitoneally injected with saline or DCA (200 mg/kg) on the probe trial. A, Mice were trained for 4 consecutive days (4 trials/d) to find the location of a hidden platform in the southwest quadrant, and the latency to escape was recorded. B–G, On day 5, a probe trial was performed in which the platform was removed and mice were allowed to swim for 60 s. B, The swim path for each group of mice was recorded and compiled into heat map representations. C–E, Measurements were taken for the total distance traveled (C), the percentage of time spent in the correct quadrant (D), and the number of times the boundary of the platform was crossed (E). F, Immediately after the probe trial, a flag trial was performed and the latency to find the flag was recorded. Data shown are the mean ± SEM. n = 9 and 10 for saline and DCA treatments, respectively. No significant differences were observed between saline-treated (sham) and DCA-injected mice.
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