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.
journal_name
Proc Natl Acad Sci U S Aauthors
Lai WS,Xu B,Westphal KG,Paterlini M,Olivier B,Pavlidis P,Karayiorgou M,Gogos JAdoi
10.1073/pnas.0604994103subject
Has Abstractpub_date
2006-11-07 00:00:00pages
16906-11issue
45eissn
0027-8424issn
1091-6490pii
0604994103journal_volume
103pub_type
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