Title : Neurochemical and behavioral effects of olanzapine in a high-risk schizophrenia mouse model
Abstract:
Schizophrenia is a mental disorder affecting behavior, cognition, and emotion. While schizophrenia is characterized by the dysregulation of dopamine in the brain, specifically the striatum, its physiology is undetermined. Olanzapine, an atypical antipsychotic, is commonly prescribed to patients with schizophrenia. The 3q29 microdeletion presents a 40>fold increased risk of schizophrenia in humans, with symptoms including executive function deficits and psychosis. It has been modeled in a CRISPR mouse (3q29del). Mice with this deletion have reduced brain volume and several behavioral impediments including deficits in social interaction, cognition, and increased sensitivity to amphetamines. Utilizing fast scan cyclic voltammetry, 3q29del mice were compared to littermate controls for striatal dopamine levels differences. Mice were surgically implanted with osmotic pumps that delivered either olanzapine (8mg/24 h) or vehicle for 9 weeks. Levels of dopamine in 3q29del mice dorsal striatum were higher than controls and presented altered demands of the dopamine recycling players, including MAO-A, MAO-B, COMT, DAT, and aldehyde dehydrogenase 1. Furthermore, 3q29del mice showed a hypolocomotive phenotype. After chronic olanzapine treatment, dopamine levels, demands of the dopamine degrading enzymes (MAO-A, MAO-B, and COMT), and locomotion were restored to resemble littermate controls. Dopamine metabolism in the striatum and locomotion is varied in 3q29del mice compared to littermate controls. Dopamine levels, dopamine degrading enzymes and locomotion can be restored with chronic olanzapine treatment. Determining the effects of antipsychotic medications in animal models with a high-risk schizophrenia genetic variant ultimately may decrease the trial-and-error paradigm often used to prescribe medications to patients.
Audience Take Away Notes:
- My presentation reignites the importance of studying the dopamine hypothesis in schizophrenia research and showcases a novel pipeline to study the disease.
- My research utilizes the recently validated 3q29 microdeletion mouse which is a high-risk schizophrenia model that leads to a 40-fold increased chance of schizophrenia development in human patients.
- The presentation shows how studying schizophrenia by its genetic background and drug interactions can be a viable research plan.
- Scientists can begin conversations regarding neurobiology dependent on genetic models of schizophrenia and pharmaceutical compatibility.
- Medical care providers can short list of medications that have higher chances of treating patients’ conditions with more efficacy. - This research can model how to study other diseases where dopamine metabolism is dysfunctional such as OCD, addiction, and even Tourette’s Syndrome.
