Overexpression of DISC1 via adeno-associated virus (serotype 8, AAV8) in the hippocampus of 8-month-old APP/PS1 transgenic mice for 4 months rescues cognitive deficits, synaptic loss, and Aβ plaque accumulation, in a way dependent on the interaction of DISC1 with LC3.
These results indicate that DISC1 attenuates Aβ generation and cognitive deficits of APP/PS1 transgenic mice through promoting lysosomal degradation of BACE1.
In conclusion, DISC1 gene variations may affect the course of cognitive deficits found in patients suffering from the first episode of non-affective psychosis.
These findings indicate that truncations of Disc1 alter glutamatergic and GABAergic neurotransmission both commonly and differently in the models and some of the effects are sex-specific, revealing how altered Disc1 expression may contribute to behavioral disruptions and cognitive deficits of SZ.
Disrupted in Schizophrenia 1 (DISC1) is a schizophrenia risk gene associated with cognitive deficits in both schizophrenics and the normal ageing population.
Thus, DISC1 and its pathways support the neurodevelopmental hypothesis of schizophrenia and provide a mechanistic explanation for the characteristic cognitive deficits.
After reviewing principles important for the selection of genes, neuroimaging techniques, and subjects, we describe how imaging-genetics investigations have helped clarify the contribution of five candidate genes (COMT, GRM3, G72, DISC1, and BDNF) to cognitive deficits in schizophrenia.