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

Area of Science:

• Neuroscience
• Molecular Biology
• Pharmacology

Background:

• Mutated DISC1 protein is linked to schizophrenia and psychiatric disorders.
• Microtubule stabilization is a potential neuroprotective strategy for schizophrenia.
• The ADNP-derived peptide NAP contains a SxIP motif crucial for microtubule dynamics and neuroprotection.

Purpose of the Study:

• To investigate the neuroprotective potential of NAP and Risperidone in a DISC1 mouse model.
• To explore the effects of these treatments on cognitive and anxiety-related behaviors.
• To examine the impact on Foxp2 gene expression, relevant to language function.

Main Methods:

• Utilized a mouse model with mutated DISC1.
• Administered NAP peptide and/or Risperidone.
• Assessed object recognition, anxiety behaviors, and hippocampal Foxp2 transcript levels.
• Doxycycline was used to block mutated DISC1 expression.

Main Results:

• Both NAP and Risperidone ameliorated object recognition deficits in DISC1 mice.
• NAP reduced anxiety, while Risperidone did not.
• Doxycycline did not reverse the observed phenotypes.
• NAP, Risperidone, and their combination significantly reduced elevated Foxp2 transcripts in the hippocampus.

Conclusions:

• NAP and Risperidone show therapeutic potential for schizophrenia, particularly for cognitive and language impairments.
• The combination of NAP and Risperidone may offer a protective strategy against language disturbances in schizophrenia.
• Microtubule-targeting agents like NAP and Risperidone warrant further investigation for psychiatric disorders.