Epub – Neuropsychopharmacology
Expression of actin- and oxidative phosphorylation-related transcripts across the cortical visuospatial working memory network in unaffected comparison and schizophrenia subjects

Jan 15, 2022

Kimoto S, Hashimoto T, Berry KJ, Tsubomoto M, Yamaguchi Y, Enwright JF, Chen K, Kawabata R, Kikuchi M, Kishimoto T, Lewis DA

Visuospatial working memory (vsWM), which is impaired in schizophrenia (SZ), is mediated by a distributed cortical network. In one node of this network, the dorsolateral prefrontal cortex (DLPFC), altered expression of transcripts for actin assembly and mitochondrial oxidative phosphorylation (OXPHOS) have been reported in SZ. To understand the relationship between these processes, and the extent to which similar alterations are present in other regions of vsWM network in SZ, a subset of actin- (CDC42, BAIAP2, ARPC3, and ARPC4) and OXPHOS-related (ATP5H, COX4I1, COX7B, and NDUFB3) transcripts were quantified in DLPFC by RNA sequencing in 139 SZ and unaffected comparison (UC) subjects, and in DLPFC and three other regions of the cortical vsWM network by qPCR in 20 pairs of SZ and UC subjects. By RNA sequencing, levels of actin- and OXPHOS-related transcripts were significantly altered in SZ, and robustly correlated in both UC and SZ subject groups. By qPCR, cross-regional expression patterns of these transcripts in UC subjects were consistent with greater actin assembly in DLPFC and higher OXPHOS activity in primary visual cortex (V1). In SZ, CDC42 and ARPC4 levels were lower in all regions, BAIAP2 levels higher only in V1, and ARPC3 levels unaltered across regions. All OXPHOS-related transcript levels were lower in SZ, with the disease effect decreasing from posterior to anterior regions. The differential alterations in markers of actin assembly and energy production across regions of the cortical vsWM network in SZ suggest that each region may make specific contributions to vsWM impairments in the illness.

Kimoto S, Hashimoto T, Berry KJ, Tsubomoto M, Yamaguchi Y, Enwright JF, Chen K, Kawabata R, Kikuchi M, Kishimoto T, Lewis DA. Neuropsychopharmacology. 2022 Jan 15. doi: 10.1038/s41386-022-01274-9. [Epub ahead of print] PubMed PMID: 35034100.


Laboratory of David A. Lewis, MD

Researching the neural circuitry of the prefrontal cortex and related brain regions, and the alterations of this circuitry in schizophrenia.



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UPMC Western Psychiatric Hospital
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University of Pittsburgh
Department of Psychiatry
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Pittsburgh, PA 15213-2593