title: Akt1 deficiency affects neuronal morphology and predisposes to abnormalities in prefrontal cortex functioning.
abstract: There is accumulating evidence that AKT signaling plays a role in the pathogenesis of schizophrenia. We asked whether Akt1 deficiency in mice results in structural and functional abnormalities in prefrontal cortex (PFC). Exploratory transcriptional profiling revealed concerted alterations in the expression of PFC genes controlling synaptic function, neuronal development, myelination, and actin polymerization, and follow-up ultrastructural analysis identified consistent changes in the dendritic architecture of pyramidal neurons. Behavioral analysis indicated that Akt1-mutant mice have normal acquisition of a PFC-dependent cognitive task but abnormal working memory retention under neurochemical challenge of three distinct neurotransmitter systems. Thus, Akt1 deficiency creates a context permissive for gene-gene and gene-environment interactions that modulate PFC functioning and contribute to the disease risk associated with this locus, the severity of the clinical syndrome, or both.
authors.affiliation: Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
authors.forename: Wen-Sung
authors.initials: WS
authors.lastname: Lai
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Koen G C
authors.initials: KG
authors.lastname: Westphal
authors.forename: Marta
authors.initials: M
authors.lastname: Paterlini
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
authors.forename: Paul
authors.initials: P
authors.lastname: Pavlidis
authors.forename: Maria
authors.initials: M
authors.lastname: Karayiorgou
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Gogos
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D017397:Prefrontal Cortex / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency*
chemical_list: C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt