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DISC1 and PDE4B Are Interacting Genetic Factors in Schizophrenia That Regulate cAMP Signaling
The disrupted in schizophrenia 1 (DISC1) gene is disrupted by a balanced translocation in a subject diagnosed with schizophrenia and a relative with chronic psychiatric illness and a mechanistic model whereby DISC1 sequesters PDE4B in resting cells and releases it in an activated state in response to elevated cAMP is proposed.
GABAA-receptor-associated protein links GABAA receptors and the cytoskeleton
A new cellular protein, GABAA-receptor-associated protein (GABARAP), is identified, which can interact with the γ2 subunit of GAB AA receptors and suggest a mechanism for the targeting and clustering of GabAA receptors.
Activation of estrogen receptor-β regulates hippocampal synaptic plasticity and improves memory
In hippocampal slices, ERβ activation enhanced long-term potentiation, an effect that was absent in slices from ERβ knockout mice, and the data suggest that activation of ERβ can regulate hippocampal synaptic plasticity and improve hippocampus-dependent cognition.
Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia
It is shown that dysbindin and DISC1 share common PPIs suggesting they may affect common biological processes and that the function of schizophrenia risk genes may converge.
Disrupted-in-Schizophrenia-1 (DISC1) regulates spines of the glutamate synapse via Rac1
The role of the schizophrenia risk factor DISC1 in the maintenance of spine morphology and function was found to be anchored Kalirin-7 (Kal-7), regulating access to Rac1 and controlling the duration and intensity of Rac1 activation in response to NMDA receptor activation in both cortical cultures and rat brain in vivo.
Phosphodiesterase 10A Inhibitor Activity in Preclinical Models of the Positive, Cognitive, and Negative Symptoms of Schizophrenia
- S. Grauer, V. Pulito, N. Brandon
- Biology, PsychologyJournal of Pharmacology and Experimental…
- 1 November 2009
The results suggest that PDE10A inhibitors alleviate both dopaminergic and glutamatergic dysfunction thought to underlie schizophrenia, which may contribute to the broad-spectrum efficacy.
Cytoskeletal Changes Underlie Estrogen's Acute Effects on Synaptic Transmission and Plasticity
It is reported here that acute actions of estrogen are due to selective activation of an actin-signaling cascade normally used in the production of long-term potentiation (LTP), and that the deficits in plasticity arise from acute, as well as genomic, consequences of hormone loss.
Linking neurodevelopmental and synaptic theories of mental illness through DISC1
The disrupted in schizophrenia 1 (DISC1) gene was originally discovered at the breakpoint of an inherited chromosomal translocation, which segregates with major mental illnesses.
Schizophrenia-Related Neural and Behavioral Phenotypes in Transgenic Mice Expressing Truncated Disc1
Disrupted-in-Schizophrenia-1 transgenic mice exhibit increased immobility and reduced vocalization in depression-related tests, and impairment in conditioning of latent inhibition, consistent with findings in severe schizophrenia.
GABAA Receptor Phosphorylation and Functional Modulation in Cortical Neurons by a Protein Kinase C-dependent Pathway*
It is shown that the neuronal β3 subunit is basally phosphorylated on serine residues by a PKC-dependent pathway, and the main sites of phosphorylation within the neurons are likely to include Ser-408 and Ser-409, residues that are important for the functional modulation of β3-containing recombinant receptors.