DLG4 Gene Implicated in Brain Damage in Preterm Babies

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by Kevin Perez |

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cerebral palsy research

Researchers at King’s College London showed that the DLG4 gene is implicated in brain damage in preterm babies and that it may act as a modulator of inflammation in the brain throughout development.

The study, “Integrative genomics of microglia implicates DLG4 (PSD95) in the white matter development of preterm infants,” was published in the journal Nature Communications.

About 30% of preterm babies are born with brain damage that can lead to the development of conditions such as cerebral palsy or autism. Though not very well understood, this damage is associated with inflammation in the brain, especially in the microglia, a specific type of brain cells.

Now, researchers showed that DLG4, a protein present on microglial cells, seemed to play a major role in brain development and control of inflammation in preterm infants.

“We have shown that the DLG4 gene is expressed differently in microglia when a brain has been damaged by inflammation,” David Edwards, director of the Centre for the Developing Brain at King’s College London, said in a press release.

The study was a collaboration between King’s college, Inserm, Paris Diderot University, and Duke-NUS Medical School in Singapore.

Researchers used data from a mouse model of IL1-beta-induced inflammation (IL1-beta is a pro-inflammatory molecule) and substantiated their findings with human microglia and brain scans from preterm infants.

They saw differences in the expression of DLG4 on microglial cells in both mouse and human models. These differences were dependant on the stages of development and inflammation. A genetic variation in DLG4 was also found to be associated with modified brain development.

DLG4 has already been implicated in diverse brain conditions such as autism and schizophrenia.

Associate Professor Enrico Petretto from Duke-NUS Medical School said, “Given the previously acknowledged role of the DLG4 gene in brain diseases such as autism and schizophrenia, our study strengthens the link between the immune response and susceptibility to develop these brain disorders.”

With further research, DLG4 could become a good target to treat or even prevent brain damage associated with inflammation in preterm babies.

“In developing this work, we hope to provide a new avenue to study and understand how this inflammation and subsequent brain damage is caused so that scientists can work towards more effective treatments for diseases such as autism and cerebral palsy, by stopping or even preventing the inflammation associated with pre-term birth,” Edwards said.