Neurological Disorders Linked to Brain Inflammation

Researchers from the University of Maryland School of Medicine (UMSOM) may have discovered how childhood inflammation impacts brain neurons and the role this might play in disorders like autism and childhood schizophrenia.

Severe inflammation during early childhood is a known risk factor for neurodevelopmental conditions like autism spectrum disorder (ASD) and schizophrenia. Moreover, previous studies have also linked cerebellum abnormalities in infants to these conditions.

However, the links between inflammation and neuron development in the cerebellum are unclear.

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Now, researchers from the University of Maryland School of Medicine (UMSOM) have identified how inflammation impacts the growth of vulnerable brain cells in the cerebellum, which may play a crucial role in neurodevelopmental disorders. This discovery could help scientists develop potential treatments for conditions such as autism.

The study was conducted by faculty members from UMSOM's Institute for Genome Sciences (IGS), the Department of Pharmacology, and the University of Maryland-Medicine Institute of Neuroscience Discovery (UM-MIND). Their findings appear in the October issue of Science Translational Medicine.

To conduct the research, the scientists examined post-mortem brain tissues from 17 children who passed away between the ages of one and five. Eight of these children had conditions involving inflammation, while the other nine had died in accidents.

Moreover, none of the children had been diagnosed with a neurological disorder before death, and all were similar in terms of age, gender, race/ethnicity, and the time that had elapsed since their passing.

The researchers used a technique called single-cell genomics to compare the tissues of children who died of non-inflammatory causes with those who had an inflammatory condition.

Specifically, they looked at the impact of early childhood inflammation on neurons in the cerebellum. The cerebellum is a brain region responsible for motor control and higher cognitive functions, including language, social skills, and emotional regulation.

The team found that inflammation stopped neurons in the cerebellum from maturing properly.

The study also revealed that two specific and rare types of cerebellar neurons — known as Golgi and Purkinje neurons — were particularly vulnerable to the effects of brain inflammation. At the single-cell level, these neurons showed signs of premature disruption in their maturation.

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Seth Ament, an IGS scientist and Associate Professor in the Department of Psychiatry at UMSOM, explained, "Although they are rare, Purkinje and Golgi neurons play critical roles in brain development. Purkinje neurons form connections between the cerebellum and other brain regions involved in cognition and emotional control, while Golgi neurons facilitate communication between cells within the cerebellum."

Any disruptions with these neurons could explain the link to autism and schizophrenia.

The researchers also observed the gene expression in the cerebellum of children with inflammatory conditions remained "remarkably consistent."

UMSOM Dean Mark Gladwin, M.D., the Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor at UMSOM, said, "This study is one of the first to show that gene expression changes during inflammation may set the stage for later cellular dysfunction, such as reducing synaptic connectivity or altering energy metabolism."

Gladwin also says it's critical to understand these mechanisms so scientists can develop novel treatments that address the associations between inflammation and neurodevelopmental disorders.

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