Signal Transducer and Activator of Transcription 3 Activation in Hippocampal Neural Stem Cells and Cognitive Deficits in Mice Following Short-term Cuprizone Exposure

Recent studies have emphasized that adult hippocampal neurogenesis impairment may be associated with cognitive problems. Because cuprizone (CPZ), a copper-chelating reagent, was shown to decrease the production of new neurons, we aimed further understand involvement in function by using short-term (2-week) CPZ exposure paradigm. The CPZ-fed mice showed deficits, i.e., impaired sensorimotor gating and reduced social novelty preference, compared normal-fed mice. Although long-term (e.g., 5-week) paradigm found cause demyelination, encountered labeling for myelin hippocampus unaffected 2-week exposure. densities neuronal progenitor cells (NPCs) newborn granule (NGCs) were lower than mice, while those neural stem (NSCs) comparable between groups. We then examined whether might induce activation signal transducer activator transcription 3 (STAT3), which plays major role cytokine receptor signaling. phosphorylated STAT3-positive (pSTAT3+) NSCs higher pSTAT3+ NPCs/NGCs very low both Interestingly, bromodeoxyuridine-positive (BrdU+) 2 weeks after BrdU injection, BrdU+ These findings suggest inhibits differentiation into NPCs via STAT3, part underlie deficits.