RNAseq data from: Medial prefrontal cortex samples of glutamate dehydrogenase-deficient mice, stress-exposed or -naive, and their Nestin-Cre+ controls

Glutamate abnormalities in the medial prefrontal cortex (mPFC) are
associated with cognitive deficits. We previously showed that homozygous
deletion of CNS glutamate dehydrogenase 1 (Glud1), a metabolic enzyme
critical for glutamate metabolism, leads to schizophrenia-like behavioral
abnormalities and increased mPFC glutamate; mice heterozygous for CNS
Glud1 deletion (C-Glud1+/- mice) showed no cognitive or molecular
abnormalities. Here, we examined the protracted behavioral and molecular
effects of mild injection stress on C-Glud1+/- mice. We found spatial and
reversal learning deficits, as well as large-scale mPFC transcriptional
changes in pathways associated with glutamate and GABA signaling, in
stress-exposed C-Glud1+/- mice, but not in their stress-naïve or
C-Glud1+/+ littermates. Interestingly, these effects were observed several
weeks following stress exposure, and the expression levels of specific
glutamatergic and GABAergic genes differentiated between high and low
reversal learning performance. An increase in MiR203-5p expression
immediately following stress may provide a translational regulatory
mechanism to account for the delayed effect of stress exposure on
cognitive function. Our findings show that chronic glutamate abnormalities
interact with acute stress to induce cognitive deficits, and resonate with
gene x environment theories of schizophrenia. Stress-exposed C-Glud1+/-
mice may model a schizophrenia high-risk population, which is uniquely
sensitive to stress-related ‘trigger’ events.