Nav: Home

Proteins associated with schizophrenia hang around longer than previously thought

March 31, 2016

The discovery that a particular protein doesn't just give cells a job but also sticks around to tell them how to do these new assignments could provide insight into schizophrenia, as well as a neurodevelopmental disorder, according to a new study by a Drexel University research team.

The team discovered that the protein, called TCF4, remains present in cells after neurogenesis -- where they turn jobless cells into neurons. Neurons are cells in the nervous system that send specific signals to each other, and scientists believed that TCF4 degraded and disappeared at that stage. However, Drexel researchers found that TCF4 sticks around and restricts the number of synapses neurons make.

"It seems these proteins are performing double duty," said Daniel Marenda, PhD, associate professor and director of the Biology graduate program in Drexel's College of Arts and Sciences. "Not only do the proteins take a cell that doesn't have a job and give it one, but once the cell has a job, it tells that cell how to do it."

The study, "Type I bHLH Proteins Daughterless and TCF4 Restrict Neurite Branching and Synapse Formation by Repressing Neurexin in Postmiotic Neurons" was published in Cell Reports. Its first author, Mitchell D'Rozario, PhD, was Marenda's graduate student, and is now a post-doctoral researcher at Washington University School of Medicine.

While the protein at the center of the study is referred to as TCF4 in humans, rats and mice, it is called Daughterless in Drosophila, or fruit flies, where the protein's persistence was discovered.

"We found, rather unexpectedly, that the fly protein Daughterless was present in neurons, cells that already had a job. This was odd to us," Marenda said. "So we decided to investigate what Daughterless might be doing in the cells."

When they found that Daughterless was regulating the number of synapses in neurons, the team analyzed TCF4 in mice and found that it was doing the exact same thing. The protein had not disappeared, but was still present and very active.

These findings are particularly important because of the association TCF4 gene variants have with schizophrenia and Pitt-Hopkins Syndrome, a neurodevelopmental disorder.

"Mutations in TCF4 are associated with both," Marenda explained. "So we think that TCF4 is most likely involved in helping to form the proper number of synapses a cell makes, so that the information flow in the nervous system doesn't get confused and dysfunctional. When you lose these proteins, you suddenly get too many synapses and it disrupts the nervous system function."

Marenda said that there is evidence that cells making too many synapses are associated with autism. Further study of the presence of TCF4 (and Daughterless) in neurons could uncover more about the relationship between synapse number and adult nervous system function.

"Depending on the severity of the mutation's effect on TCF4, you may get differing outcomes," Marenda said. "Too severe a mutation may give you a strong effect like Pitt-Hopkins Syndrome, while other changes in the gene may increase your risk of schizophrenia. But the underlying mechanism may be similar."
-end-


Drexel University

Related Schizophrenia Articles:

First physiological test for schizophrenia and depression
Researchers have found a new way of using proteins in nerve cells to identify people with depression and schizophrenia.
The emergence of a new dopamine hypothesis of schizophrenia
Biological Psychiatry presents a special issue, 'The Dopamine Hypothesis of Schizophrenia,' dedicated to recent advances in understanding the role of dopamine signaling in schizophrenia.
Progress in refining the genetic causes of schizophrenia
An international study led by the University of Exeter Medical School has made advances in understanding the ways in which genetic risk factors alter gene function in schizophrenia.
Exercise can tackle symptoms of schizophrenia
Aerobic exercise can significantly help people coping with the long-term mental health condition schizophrenia, according to a new study from University of Manchester researchers.
In search of neurobiological factors for schizophrenia
It is impossible to predict the onset of schizophrenic psychosis.
A comparison between quetiapine and aripiprazole for treatment of schizophrenia
Schizophrenia is a common cause of incapacity and is ranked as the third most disabling illness subsequent to dementia and quadriplegia.
Four new genetic diseases defined within schizophrenia
Changes in key genes define four previously unknown conditions within schizophrenia, according to a study led by researchers from NYU Langone Medical Center published online April 28 in EBioMedicine, a Lancet journal.
Decrypting a collagen's role in schizophrenia
A small peptide generated from a collagen protein may protect the brain from schizophrenia by promoting the formation of neuronal synapses, according to a paper published in The Journal of Cell Biology.
Two in 5 individuals with schizophrenia have attempted suicide
A new study by the University of Toronto (U of T), released today, found that those with schizophrenia who'd been physically abused during childhood were five times more likely to have attempted suicide.
'Schizophrenia' does not exist, argues expert
The term 'schizophrenia,' with its connotation of hopeless chronic brain disease, should be dropped and replaced with something like 'psychosis spectrum syndrome,' argues a professor of psychiatry in The BMJ today.

Related Schizophrenia Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Bias And Perception
How does bias distort our thinking, our listening, our beliefs... and even our search results? How can we fight it? This hour, TED speakers explore ideas about the unconscious biases that shape us. Guests include writer and broadcaster Yassmin Abdel-Magied, climatologist J. Marshall Shepherd, journalist Andreas Ekström, and experimental psychologist Tony Salvador.
Now Playing: Science for the People

#513 Dinosaur Tails
This week: dinosaurs! We're discussing dinosaur tails, bipedalism, paleontology public outreach, dinosaur MOOCs, and other neat dinosaur related things with Dr. Scott Persons from the University of Alberta, who is also the author of the book "Dinosaurs of the Alberta Badlands".