How the gene that has been pegged as a major risk factor for
schizophrenia and other mood
disorders that affect millions of Americans contributes to these
diseases remains unclear. However,
the results of a new study by Johns Hopkins researchers and their
colleagues, appearing online in Cell
Sept. 6, provide a big clue by showing what this gene does in
normal adult brains.
It turns out that this gene, called disc1, makes a protein
that serves as a sort of musical
conductor for newly made nerve cells in the adult brain, guiding
them to their proper locations at the
appropriate tempo so they can seamlessly integrate into our
complex and intertwined nervous system.
If the DISC1 protein doesn't operate properly, the new nerves go
hyper.
"DISC1 plays a broader role in the development of adult
nerves than we anticipated," said
Hongjun Song, an associate professor at Johns Hopkins' Institute for Cell
Engineering. "Some previous
studies hinted that DISC1 is important for nerve migration and
extension, but our study in mice
suggests it is critical for more than that and may highlight why
DISC1 is associated with multiple
psychiatric disorders."
Added fellow author Guo li Ming, also an associate professor
at ICE, "Almost every part of the
nerve integration process speeds up. The new nerves migrate and
branch out faster than normal, form
connections with neighbors more rapidly and are even more
sensitive to electrical stimulation."
While it may not be obvious why high-speed integration would
be detrimental, Song notes that
because of the complexity of the brain, timing is critical to
ensure that new nerves are prepared to
plug into the neural network.
Ming, Song and their collaborators at the National
Institutes of Health and the University of
California, Davis tracked the abnormal movements of the
hyperactive nerve cells by injecting a
specially designed virus into a part of a mouse brain known as
the hippocampus, a region important for
learning and memory and therefore quite relevant to psychiatric
disorders. The virus would only infect
newly born cells and would both knock down the expression of the
disc1 gene and make the nerves glow
under a microscope.
Combined with other recent Johns Hopkins research that
successfully engineered mouse models
that have abnormal DISC1 and can effectively reproduce
schizophrenia symptoms such as anxiety,
hyperactivity, apathy and altered senses, these current findings
teasing out the normal role of this
protein may help unravel the causes for this complex disease.
Song and Ming add that their studies in the hippocampus--one
of the few places where new
nerves are made in the adult brain--might answer why symptoms
typically first appear in adults
despite the genetic basis of many psychiatric illnesses. They
plan on continuing their mouse work to
try and find those answers.
The research was funded by the National Institutes of
Health, McKnight Scholar Award,
Whitehall Foundation and a Klingenstein Fellowship Award in the
Neurosciences.
Authors on the paper are Jay Chang, Sundar Ganesan and Bai
Lu, all of the National Institutes
of Mental Health; Regina Faulkner, Xiao bo Liu and Hwai Jong
Cheng, all of the University of
California, Davis; and Xin Duan, Shaoyu Ge, Ju Young Kim, Yasuji
Kitabatake, Chih Hao Yang, J. Dedrick
Jordan, Dengke Ma, Cindy Liu, Ming and Song, all of Johns
Hopkins.
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