NU 2007-037

Inventors

Peter Penzes*

Short Description

Mouse model of cognitive deficits associated with aberrant formation of neural synapses 

Abstract

A Northwestern researcher has developed a mouse model that approximates human cognitive deficits. Neurodevelopmental and neuropsychiatric disorders that affect cognition are devastating illnesses that impose a large public health burden on society. Among these diseases are schizophrenia, mental retardation, autism and Alzheimer's disease, which affect people in all age groups and share a common early event in pathogenesis. Disruption of synapses is a key event in pathogenesis of all of the above-mentioned diseases, so the first step toward developing treatments is to establish valid animal models. The knock out mice generated in Prof. Penzes' laboratory show no gross brain development problems, but exhibit alterations in the hippocampus (18% smaller than controls) and cerebral cortex (~9% smaller) as well as reduced dendrite branching and spine density. Furthermore, these knock out mice have specific and significant cognitive impairments similar to what is seen in humans. This mouse model may be a useful tool for several basic and translational research avenues, and could help improve treatments for cognitive deficits.

Applications

• Studies of mechanisms driving cognitive deficits and intermediate cognitive impairment phenotypes
• Development of therapeutics designed to stimulate synapse growth and plasticity

Advantages

• First animal model for synapse dysgenesis-related cognitive deficits
• Approximates several human disorders

Publications

Cahill ME, Xie Z, Day M, Photowala H, Barbolina MV, Miller CA, Weiss C, Radulovic J, Sweatt JD, Disterhoft JF, Surmeier DJ (2009) Kalirin Regulates Cortical Spine Morphogenesis and Disease Related Behaviral Phenotypes, Proceedings of the National Academy of Sciences of the United States of America, 106: 13058-63.