Opposite changes in phosphoinositide-specific phospholipase C immunoreactivity in the left prefrontal and superior temporal cortex of patients with chronic schizophrenia

Knockdown of phospholipase C-β1 in the medial prefrontal cortex of male mice impairs working memory among multiple schizophrenia endophenotypes

“…39,40 In addi tion, decreased PLCβ1 expression in the brains of patients with schizophrenia, particularly in the DLPFC, has suggested the possible pathogenic involvement of PLCβ1 in schizo phrenia. 13,14,21 Here, using mPFClimited, shRNAmediated silencing of PLCβ1, we generated a mouse model that mimics the decrease of PLCβ1 in the DLPFC of patients with schizophrenia. Behavioural characterization of these model mice revealed that mPFCspecific knockdown of PLCβ1 induced only the impaired working memory phenotype without producing the altered anxiety or other schizophrenia endophenotypes previously observed in PLCβ1 −/− mice.…”

“…4,[9][10][11][12] Moreover, decreased expression of PLCβ1 has been detected in the brains of patients with schizophrenia. [13][14][15][16][17][18] Schizophrenia symptoms are categorized into 3 major types 19,20 -positive, negative and cognitive -and a majority of these symptoms have been observed as endophenotypes in PLCβ1null (PLCβ1 −/− ) mice. [9][10][11][12] These symptoms include increased locomotion, impaired social behaviour, impaired prepulse inhibition (PPI), and impaired working memory.…”

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

“…PLC-b1 has been shown to have altered expression in schizophrenic individuals. 26 Moreover, the PLC-b1 null mutation disrupts signaling through multiple pathways implicated in schizophrenic pathogenesis, such as the muscarinic cholinergic pathways, resulting in a comprehensive behavioral phenotype which correlates with that observed in the human condition. [68][69][70][71][72] We show that this mouse model exhibits numerous endophenotypes characteristic of schizophrenia including locomotor hyperactivity, sensorimotor gating deficits and cognitive deficits.…”

“…[23][24][25] It is, therefore, significant that PLC-b1 represents a point of convergence for these signaling pathways and that levels of the protein have been shown to be altered in the cortex of chronic schizophrenic patients, increasing in the prefrontal cortex and decreasing in the superior temporal gyrus. 26 The outcomes of disrupted PLC-b1 signaling can be studied in PLC-b1 knockout (KO) mice, 9 which have been shown to have abnormal cortical maturation including aberrant barrel formation in the somatosensory cortex 3 as well as disrupted synapse formation and dendritic spine morphology. 27 Behaviorally, spatial memory deficits have been identified 28,29 but a more complete behavioral phenotype has not yet been established.…”

Association of RGS2 Gene Polymorphisms with Suicide and Increased RGS2 Immunoreactivity in the Postmortem Brain of Suicide Victims

“…Brain tissue samples were prepared as described previously (Lin et al, 1999). Proteins were electrophoresed in a 15% SDS-polyacrylamide gel (5 mg/lane).…”