Table 2. Influence of chronic chemogenetic activation of CamKIIα-positive forebrain excitatory neurons during the early postnatal window on the total levels of metabolites relative to [2-13C]glycine in the hippocampus and cortex in adult male mice.
[1,6-13C]glucose Infusion | ||||||||||||
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Concentration of brain metabolites determined relative to [2-13C]glycine (µmol/g) | ||||||||||||
Brain Region | Group | Glu | GABA | Gln | Asp | NAA | Ala | Lac | Ino | Tau | Cho | Cre |
Hippocampus | Vehicle | 13.5 ± 0.3 | 3.6 ± 0.2 | 5.0 ± 0.1 | 2.3 ± 0.1 | 8.9 ± 0.1 | 0.7 ± 0.1 | 3.0 ± 0.6 | 7.3 ± 0.2 | 8.6 ± 0.2 | 2.3 ± 0.1 | 13.5 ± 0.2 |
PNCNO | 13.7 ± 0.3 | 3.7 ± 0.2 | 4.8 ± 0.1 | 2.5 ± 0.1 | 9.0 ± 0.1 | 0.6 ± 0.1* | 2.3 ± 0.2 | 7.5 ± 0.2 | 8.5 ± 0.2 | 2.3 ± 0.1 | 13.5 ± 0.3 | |
Cortex | Vehicle | 13.5 ± 0.3 | 3.4 ± 0.1 | 4.7 ± 0.1 | 2.9 ± 0.1 | 9.5 ± 0.4 | 0.7 ± 0.1 | 7.0 ± 1.3 | 6.0 ± 0.2 | 9.1 ± 0.1 | 2.0 ± 0.1 | 12.9 ± 0.1 |
PNCNO | 14.0 ± 0.2 | 3.3 ± 0.1 | 4.5 ± 0.1 | 3.2 ± 0.1$ | 9.6 ± 0.4 | 0.6 ± 0.1 | 5.3 ± 0.5 | 6.0 ± 0.1 | 9.1 ± 0.2 | 2.1 ± 0.1 | 12.9 ± 0.2 |
Chronic CNO-mediated hM3Dq DREADD activation in CamKIIα-positive forebrain excitatory neurons was achieved using bigenic CamKIIα-tTA::TetO-hM3Dq mouse pups that were fed CNO (PNCNO; 1 mg/kg) or vehicle from P2 to P14 and then left undisturbed for 3 months prior to metabolic analysis performed in adulthood on male mice and NMR spectroscopy on the hippocampus and cortex was performed to acquire 1H-[12C + 13C] spectra. The concentration of metabolites was determined relative to [2-13C]glycine. Glu: Glutamate; GABA: γ-aminobutyric acid; Gln: Glutamine; Asp: Aspartate; NAA: N-acetylaspartate; Suc: Succinate; Ala: Alanine; Lac: Lactose; Ino; Inositol; Tau: Taurine; Cho: Choline; Cre: Creatine. Results are expressed as the mean ± S.E.M (n = 7 per group). *p<0.05, $p=0.06; as compared to vehicle-treated controls using the two-tailed, unpaired Student’s t-test.