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. 2022 Apr 4;3(3):418–429. doi: 10.1016/j.bpsgos.2022.03.010

Figure 1.

Figure 1

BCL11BKO MSNs and CTX neurons manifest signs of mitochondrial dysfunction and abnormal intracellular Ca2+ regulation. (A) Schematic of MSN, CTX, and mDA neuron differentiation protocols. (B–D) Mitochondrial membrane potential as measured by JC-1 dye ratio at rest and after 24 hours treatment with 1000 μM SNAP in (B) MSNs, (C) CTX neurons, and (D) mDA neurons at 40 days of differentiation (two-way analysis of variance with post hoc Bonferroni test; MSN: genotype, F1,42 = 30.552, p = 1.9 × 10−6; treatment, F1,42 = 15.601, p = 2.9 × 10−4; from left, in black: ∗∗∗p = 4.6 × 10−4, 2.4 × 10−4; ∗p = .024; in red: ∗∗p = .001; CTX: treatment, F1,20 = 8.863, p = .007; in red: ∗p = .013; mDA: treatment, F1,20 = 29.941, p = 2.3 × 10−5; in black: ∗∗∗p = 4.9 × 10−4; in red: ∗∗p = .001). (E–G) Significantly increased store-operated channel-mediated Ca2+ entry in response to thapsigargin) is observed in BCL11BKO vs. control MSNs and CTX neurons but not mDA neurons, as demonstrated by ΔF/F0 traces (left) and quantification of maximum ΔF/F0 (right) (Mann-Whitney U test; MSN: U = 63,008.5, ∗∗∗p = 2.4 × 10−116; CTX: U = 33,264, ∗∗∗p = 5.8 × 10−192). (H–J) Greater Ca2+ signals are induced in BCL11BKO vs. control MSNs and CTX neurons in response to external KCl, as demonstrated by ΔF/F0 traces (left) and quantification of maximum ΔF/F0 (right) (Mann-Whitney U test; MSN: U = 515,797, ∗∗∗p = 3.3 × 10−88; CTX: U = 344,257, ∗∗∗p = 1.5 × 10−54). All line graphs and dot plots depict mean ± SEM for each genotype. Box-and-whisker plots depict data for each genotype (center line, median; +, mean; box limits, upper and lower quartiles; whiskers, 2.5 and 97.5 percentiles). Means for individual clones are indicated by red-shaded circles next to BCL11BKO data. See also Figures S1 and S2. BDNF, brain-derived neurotrophic factor; CTX, cortical glutamatergic; KCI, potassium chloride; KO, knockout; LDN, LDN-193189; mDA, midbrain dopaminergic; MSNs, medium spiny neurons; n.s., not significant; SB, SB431542; SHH, sonic hedgehog; Tg, thapsigargin.