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Published on: May 15, 2016
A New Three-Hit Mouse Model of Neurodevelopmental Disorder with Cognitive Impairments and Persistent Sociability
Imane Mouffok1, Caroline Lahogue1, Thomas Cailly2,3,4
1Department of Health, Normandie Université, UNICAEN (Université de Caen Normandie), INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 1075 COMETE, Campus 5, CYCERON, FHU (Fédération Hospitalo-Universitaire) A2M2P, CHU (Centre Hospitalo-Universitaire) Caen, 14000 Caen, France.
A new three-hit mouse model combining genetic susceptibility, early stress, and phencyclidine (PCP) treatment effectively replicates schizophrenia-like symptoms, particularly negative symptoms, aiding in developing better treatments.
Area of Science:
- Neuroscience
- Psychiatry
- Animal Models
Background:
- Schizophrenia's cognitive and negative symptoms lack effective treatments.
- Refining animal models is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To develop a robust three-hit mouse model for schizophrenia.
- To assess the construct and face validity of this model for neurodevelopmental disorders.
Main Methods:
- A three-hit model combining serine racemase deletion, maternal separation, and phencyclidine (PCP) administration.
- Behavioral assessments in female mice to evaluate positive-like, negative-like, and cognitive symptoms.
Main Results:
- Three-hit mice exhibited persistent hyperlocomotion (positive-like symptoms).
- Social behavior deficits (negative-like symptoms) were persistent.
- Spatial working memory deficits (cognitive symptoms) were not persistent.
Conclusions:
- The three-hit model effectively captures key schizophrenia-like symptoms, especially negative symptoms.
- This model demonstrates strong construct and face validity.
- The findings support glutamate dysfunction's role in the behavioral pathology of schizophrenia.
