title: Expression of p21-activated kinases 1 and 3 is altered in the brain of subjects with depression.
abstract: The p21-activated kinases (PAKs) of group I are the main effectors for the small Rho GTPases, critically involved in neurodevelopment, plasticity and maturation of the nervous system. Moreover, the neuronal complexity controlled by PAK1/PAK3 signaling determines the postnatal brain size and synaptic properties. Stress induces alterations at the level of structural and functional synaptic plasticity accompanied by reductions in size and activity of the hippocampus and the prefrontal cortex (PFC). These abnormalities are likely to contribute to the pathology of depression and, in part, reflect impaired cytoskeleton remodeling pointing to the role of Rho GTPase signaling. Thus, the present study assessed the expression of the group I PAKs and their activators in the brain of depressed subjects. Using quantitative polymerase chain reaction (qPCR), mRNA levels and coexpression of the group I PAKs: PAK1, PAK2, and PAK3 as well as of their activators: RAC1, CDC42 and ARHGEF7 were examined in postmortem samples from the PFC (n=25) and the hippocampus (n=23) of subjects with depression and compared to control subjects (PFC n=24; hippocampus n=21). Results demonstrated that mRNA levels of PAK1 and PAK3, are significantly reduced in the brain of depressed subjects, with PAK1 being reduced in the PFC and PAK3 in the hippocampus. No differences were observed for the ubiquitously expressed PAK2. Following analysis of gene coexpression demonstrated disruption of coordinated gene expression in the brain of subjects with depression. Abnormalities in mRNA expression of PAK1 and PAK3 as well as their altered coexpression patterns were detected in the brain of subjects with depression.
authors.affiliation: Instituto de Investigaciones Biotecnológicas, CONICET-UNSAM, 1650 San Martin, Argentina. Electronic address: beata@iibintech.com.ar.
authors.forename: Beata
authors.initials: B
authors.lastname: Fuchsova
authors.affiliation: Instituto de Investigaciones Biotecnológicas, CONICET-UNSAM, 1650 San Martin, Argentina.
authors.forename: Anabel
authors.initials: A
authors.lastname: Alvarez Juliá
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Hooriyah S
authors.initials: HS
authors.lastname: Rizavi
authors.affiliation: Instituto de Investigaciones Biotecnológicas, CONICET-UNSAM, 1650 San Martin, Argentina.
authors.forename: Alberto Carlos
authors.initials: AC
authors.lastname: Frasch
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Ghanshyam N
authors.initials: GN
authors.lastname: Pandey
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D015331:Cohort Studies; D003866:Depressive Disorder / Q000201:enzymology* / Q000473:pathology; D005260:Female; D020690:GTPase-Activating Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors / Q000378:metabolism; D012727:Sex Characteristics; D055815:Young Adult; D054462:p21-Activated Kinases / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C514543:ARHGAP31 protein, human; C576606:ARHGEF7 protein, human; D020690:GTPase-Activating Proteins; D010750:Phosphoproteins; C107953:RAC1 protein, human; D012333:RNA, Messenger; D064067:Rho Guanine Nucleotide Exchange Factors; C515903:PAK1 protein, human; C515907:PAK2 protein, human; C515911:PAK3 protein, human; D054462:p21-Activated Kinases; D020830:rac1 GTP-Binding Protein
keywords: coexpression analysis; mRNA expression; p21-activated kinase; postmortem; qPCR