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

Sinaya Vaisburd, Zeev Shemer, Adva Yeheskel, Eliezer Giladi, Illana Gozes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number16300
JournalScientific Reports
Volume5
DOIs
StatePublished - 10 Nov 2015

Funding

FundersFunder number
Adams family
Elton Laboratory for Molecular Neuroendocrinology
Canadian Friends of Tel Aviv University
AAMN Foundation
Ministry of Science, Technology and Space
Israel Science Foundation
Tel Aviv University

    Fingerprint

    Dive into the research topics of 'Risperidone and NAP protect cognition and normalize gene expression in a schizophrenia mouse model'. Together they form a unique fingerprint.

    Cite this