Glutamate-glutamine homeostasis is perturbed in neurons and astrocytes derived from patient iPSC models of frontotemporal dementia

Table 1 Glutamine content is significantly diminished in FTD3 neurons derived from hiPSCs

substrates present during incubation	*amino acid*	*isogenic control neurons*	*FTD 3 neurons*	*P value*
amounts (nmol/mg protein)
*[U-* ¹³*C]glucose*	Glutamine	12 ± 1.7	6 ± 1.3	*0.005*	^a
*[U-* ¹³*C]glucose*	Glutamate	61 ± 4.3	51 ± 2.9	0.14
*[U-* ¹³*C]glutamine* + glucose	Glutamine	18 ± 1.3	13 ± 1.5	*0.008*	^a
*[U-* ¹³*C]glutamine* + glucose	Glutamate	68 ± 5.1	59 ± 4.0	0.26
*[U-* ¹³*C]glutamate* + glucose	Glutamine	14 ± 1.5	7 ± 0.7	*0.024*	^a
*[U-* ¹³*C]glutamate* + glucose	Glutamate	185 ± 18.8	185 ± 18.8	1.00

Cellular content of amino acids in cultured neurons derived from hiPSCs. Cultured neurons were incubated for 90 min with 2.5 mM [U-13C] glucose or 0.25 mM [U-13C] glutamate or 0.5 mM [U-13C] glutamine in the presence of 2.5 mM unlabeled glucose. Cell extracts were analyzed by HPLC for determination of amino acid content. Results are mean ± SEM from 3 individuals (6 different cultures of hiPSCs-derived neurons/condition). Unpaired multiple t test followed by Bonferroni-Dunn post hoc test was used for statistical evaluations. P values were calculated comparing FTD3 neurons agains isogenic controls, ^a denotes statistical significance