Fig. 5
From: Loss of mitochondrial enzyme GPT2 leads to reprogramming of synaptic glutamate metabolism
Decreases in released glutamate are restored by alpha-ketoglutarate in Gpt2-null synaptosomes. A Glutamate levels are restored by alpha-ketoglutarate in Gpt2-null synaptosomes. Each dot represents a different synaptosome sample obtained from wild-type (black) or Gpt2-null (red) mice at P18. Wild-type vs. Gpt2-null no supplement: ***P < 0.001; + alpha-ketoglutarate: ***P < 0.001. Wild-type no supplement vs. Gpt2-null + alpha-ketoglutarate: P = 0.99. Wild-type no supplement vs. wild-type + alpha-ketoglutarate: ***P < 0.001. Wild-type vs. Gpt2-null + alpha-ketoglutarate: ***P < 0.001. n.s. = statistically non-significant. A two-way ANOVA was performed with Tukey’s multiple comparison correction and the reported p-values are adjusted p-values. B Glutamate levels are not restored by alanine in Gpt2-null synaptosomes. Each dot represents a different synaptosome sample obtained from wild-type (black) or Gpt2-null (red) mice at P18. Wild-type vs. Gpt2-null no supplement: ***P < 0.001; + alanine: *P = 0.01. Wild-type no supplement vs. Gpt2-null + alanine: *P = 0.02. Wild-type no supplement vs. alanine: P = 0.16. Gpt2-null no supplement vs. alanine: P = 0.10. n.s. = statistically non-significant. A two-way ANOVA was performed with Tukey’s multiple comparison correction and the reported p-values are adjusted p-values. C Glutamate levels are restored by alanine and alpha-ketoglutarate combined supplementation in Gpt2-null synaptosomes. Each dot represents a different synaptosome sample obtained from wild-type (black) or Gpt2-null (red) mice at P18. Wild-type vs. Gpt2-null no supplement: ***P < 0.001. Wild-type vs. Gpt2-null + alanine + alpha-ketoglutarate: ***P < 0.001. Wildtype no supplement vs. Gpt2-null + alanine + alpha-ketoglutarate: P = 0.84. Wild-type no supplement vs. + alanine + alpha-ketoglutarate: ***P < 0.001. Gpt2-null no supplement vs. + alanine + alpha-ketoglutarate: ***P < 0.001. n.s. = statistically non-significant. A two-way ANOVA was performed with Tukey’s multiple comparison correction and the reported p-values are adjusted p-values. D Released GABA levels were unchanged with or without alpha-ketoglutarate in Gpt2-null synaptosomes. Each dot represents a different synaptosome sample obtained from wild-type (black) or Gpt2-null (red) mice at P18. Wild-type vs. Gpt2-null no supplement: P = 0.59. Wild-type vs. Gpt2-null + alpha-ketoglutarate: P = 0.23. A two-way ANOVA was performed with Tukey’s multiple comparison correction and the reported p-values are adjusted p-values. E Released GABA levels with or without alanine. Each dot represents a different synaptosome sample obtained from wild-type (black) or Gpt2-null (red) mice at P18. Wild-type vs. Gpt2-null no supplement: P = 0.59. Wild-type vs. Gpt2-null + alanine P = 0.63. A two-way ANOVA was performed with Tukey’s multiple comparison correction and the reported p-values are adjusted p-values. F Released GABA levels with or without alanine and alpha-ketoglutarate combined supplementation. Each dot represents a different synaptosome sample obtained from wild-type (black) or Gpt2-null (red) mice at P18. Wild-type vs. Gpt2-null no supplement: 0.87. Wild-type vs. Gpt2-null + alanine + alpha-ketoglutarate P = 0.69. A two-way ANOVA was performed with Tukey’s multiple comparison correction and the reported p-values are adjusted p-values. Data in panel A&B&D&E were derived from the same cohort of animals, and data in panel C&F were derived from a separate cohort of animals