Behavioral, Neurophysiological, and Synaptic Impairment in a Transgenic Neuregulin1 (NRG1-IV) Murine Schizophrenia Model.
Francesco PapaleoFeng YangClare PatersonSara PalumboGregory V CarrYanhong WangKirsten FloydWenwei HuangCraig J ThomasJingshan ChenDaniel R WeinbergerAmanda J LawPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2017)
Schizophrenia is a disabling psychiatric disorder with neurodevelopmental origins. Genes that increase risk for schizophrenia have been identified. Understanding how these genes affect brain development and function is necessary. This work is the first report of a newly generated humanized transgenic mouse model engineered to express human NRG1-IV, an isoform of the NRG1 (Neuregulin 1) gene that is increased in the brains of patients with schizophrenia in association with genetic risk. Using behavioral neuroscience, molecular biology, electrophysiology, and pharmacology, we identify a role for NRG1-IV in learning, memory, and cognition and determine that this relates to brain excitatory-inhibitory balance and changes in ErbB4/PI3K/AKT signaling. Moreover, the study further highlights the potential of targeting the PI3K pathway for the treatment of schizophrenia.
Keyphrases
- bipolar disorder
- genome wide
- pi k akt
- mouse model
- white matter
- signaling pathway
- genome wide identification
- cell proliferation
- endothelial cells
- copy number
- mental health
- cell cycle arrest
- dna methylation
- mild cognitive impairment
- gene expression
- bioinformatics analysis
- genome wide analysis
- blood brain barrier
- drug delivery
- pluripotent stem cells
- climate change
- induced pluripotent stem cells