Altered hippocampal gene expression and structure in transgenic mice overexpressing neuregulin 1 (Nrg1) type I

AbstractTransgenic mice overexpressing the type I isoform of neuregulin 1 (Nrg1; NRG1) have alterations in hippocampal gamma oscillations and an age-emergent deficit in hippocampus-dependent spatial working memory. Here, we examined the molecular and morphological correlates of these findings. Microarrays showed over 100 hippocampal transcripts differentially expressed inNrg1tg-type Imice, with enrichment of genes related to neuromodulation and, in older mice, of genes involved in inflammation and immunity.Nrg1tg-type Imice had an enlarged hippocampus with a widened dentate gyrus. The results show thatNrg1type I impacts on hippocampal gene expression and structure in a multifaceted and partly age-related way, complementing the evidence implicatingNrg1signaling in aspects of hippocampal function. The findings are also relevant to the possible role ofNRG1signaling in the pathophysiology of schizophrenia or other disorders affecting this brain region.