California Institute of Technology (Caltech) researchers have found that lack of protein densin-180 could lead to schizophrenia and autism spectrum disorders.
The protein is abundant in the synapses of the brain - synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell.
AdvertisementDensin-180 sticks to and binds together several other proteins in a part of the neuron that's at the receiving end of a synapse and is called the postsynapse.
A team led by Mary Kennedy, the Allen and Lenabelle Davis Professor of Biology at Caltech created mutations in mice without the gene for protein densin-180. "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 Kennedy.
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," Kennedy says.
Animals sometimes exhibit abnormal behaviors similar to those seen in humans with psychological disorders. Such behaviors are called endophenotypes
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 researchers point out in the study that appears in the Journal of Neuroscience.