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Sci Rep. 2015 Nov 10;5:16300. doi: 10.1038/srep16300.

Risperidone and NAP protect cognition and normalize gene expression in a schizophrenia mouse model.

Author information

1
The Lily and Avraham Gildor Chair for the Investigation of Growth Factors, The Elton Laboratory for Neuroendocrinology, Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Sagol School of Neuroscience and Adams Super Center for Brain Studies, Tel Aviv University 69978, Israel.
2
The Bioinformatics Unit, George S. Wise Faculty of Life Sciences, Tel Aviv University 69978, Israel.

Abstract

Mutated disrupted in schizophrenia 1 (DISC1), a microtubule regulating protein, leads to schizophrenia and other psychiatric illnesses. It is hypothesized that microtubule stabilization may provide neuroprotection in schizophrenia. The NAP (NAPVSIPQ) sequence of activity-dependent neuroprotective protein (ADNP) contains the SxIP motif, microtubule end binding (EB) protein target, which is critical for microtubule dynamics leading to synaptic plasticity and neuroprotection. Bioinformatics prediction for FDA approved drugs mimicking SxIP-like motif which displace NAP-EB binding identified Risperidone. Risperidone or NAP effectively ameliorated object recognition deficits in the mutated DISC1 mouse model. NAP but not Risperidone, reduced anxiety in the mutated mice. Doxycycline, which blocked the expression of the mutated DISC1, did not reverse the phenotype. Transcripts of Forkhead-BOX P2 (Foxp2), a gene regulating DISC1 and associated with human ability to acquire a spoken language, were increased in the hippocampus of the DISC1 mutated mice and were significantly lowered after treatment with NAP, Risperidone, or the combination of both. Thus, the combination of NAP and standard of care Risperidone in humans may protect against language disturbances associated with negative and cognitive impairments in schizophrenia.

PMID:
26553741
PMCID:
PMC4639790
DOI:
10.1038/srep16300
[Indexed for MEDLINE]
Free PMC Article

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