Mouse Study: Missing Gene and Abnormal Behavior Linked
Although many mental illnesses are uniquely human, animals sometimes exhibit abnormal behaviors similar to those seen in humans with psychological disorders. Such behaviors are called endophenotypes.
Now, researchers at the California Institute of Technology have found that mice lacking a gene that encodes a particular protein found in the synapses of the brain display a number of endophenotypes associated with schizophrenia and autism spectrum disorders.
In the study, which was published in The Journal of Neuroscience, the researchers created mutations in mice so that they were missing the gene for a protein called densin-180, which is abundant in the synapses of the brain.
These electro-chemical connections enable the formation of networks between the brain’s neurons. This protein sticks to and binds together several other proteins in a part of the neuron that is at the receiving end of a synapse, called the postsynapse.
“Our work indicates that densin-180 helps to hold together a key piece of regulatory machinery in the postsynaptic part of excitatory brain synapses,” says Mary Kennedy, the Allen and Lenabelle Davis Professor of Biology at Caltech, who was the senior author on the study.
In mice lacking densin-180, the researchers found decreased amounts of some of the other regulatory proteins normally located in the postsynapse. Kennedy and her colleagues were especially intrigued by a marked decrease in the amount of a protein called DISC1.
“A mutation that leads to loss of DISC1 function has been shown to predispose humans to development of schizophrenia and bipolar disorder,” Kennedy says.
In the study, the researchers compared the behavior of typical mice with that of mice lacking densin. Those without densin displayed impaired short-term memory, hyperactivity in response to novel or stressful situations, a deficit of normal nest-building activity, and higher levels of anxiety.
“Studies of mice with schizophrenia and autism-like features have reported similar behaviors,” Kennedy notes. “We do not know precisely how the molecular defect leads to the behavioral endophenotypes. That will be our work going forward. The molecular mechanistic links between a gene defect and defective behavior are complicated and, as yet, mostly unknown. Understanding them goes to the very heart of understanding brain function.”
The findings point to the need for a better understanding of the interactions that occur between proteins at synapses, she adds. Studies of these interactions could provide information needed to screen for new and better pharmaceuticals for the treatment of mental illnesses.
“This study really reinforces the idea that small changes in the molecular structures at synapses are linked to major problems with behavior,” Kennedy says.
Wood, J. (2018). Mouse Study: Missing Gene and Abnormal Behavior Linked. Psych Central. Retrieved on July 16, 2020, from https://psychcentral.com/news/2011/11/25/mouse-study-missing-gene-and-abnormal-behavior-linked/31872.html