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

Lai WS,Xu B,Westphal KG,Paterlini M,Olivier B,Pavlidis P,Karayiorgou M,Gogos JA

doi

10.1073/pnas.0604994103

subject

Has Abstract

pub_date

2006-11-07 00:00:00

pages

16906-11

issue

45

eissn

0027-8424

issn

1091-6490

pii

0604994103

journal_volume

103

pub_type

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