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October 2023
Katrin C
Severe inflammation in early childhood has long been established as a risk factor for neurodevelopmental disorders like autism spectrum disorders and schizophrenia. Researchers from the University of Maryland School of Medicine (UMSOM) have recently observed how inflammation alters the development of crucial brain cells, providing potential pathways for future treatments.
This study focused on the cerebellum, a brain region responsible for motor control and higher cognitive functions such as language, social skills, and emotional regulation. The team, led by scientists from UMSOM's Institute for Genome Sciences, Department of Pharmacology, and UM-MIND, utilized cutting-edge single-cell genomics to examine post-mortem brain tissues of 17 children aged one to five years. Eight of these children had died from conditions involving inflammation, while nine had died due to accidents. The researchers aimed to uncover the impact of inflammation on the development of cerebellar neurons and glia.
What they discovered was remarkable: inflammation in early childhood prevented specific neurons in the cerebellum, particularly the Golgi and Purkinje neurons, from maturing completely. These neurons are crucial in forming synaptic connections and coordinating communication within the cerebellum and other brain regions involved in cognition and emotional control. Disruption in the maturation of these neurons due to inflammation could potentially explain the link between early inflammation and neurodevelopmental disorders like autism spectrum disorders and schizophrenia. By utilizing single-nucleus RNA sequencing, the researchers could study brain changes at the cellular level. This approach provided insights into the effects of inflammation on specific neuron types during crucial stages of brain development. Dr. Seth Ament, one of the co-leaders of the research, emphasized the novelty of their approach, stating, "This has never been done before in this age group and in the context of inflammation. The gene expression in the cerebella of children with inflammation was remarkably consistent." Dr. Margaret McCarthy, another co-leader of the study, highlighted the importance of their focus on the cerebellum, a region that, despite its significance, had remained understudied until now.
These findings have far-reaching implications for understanding the complex interplay between genetics, environment, and neurodevelopmental disorders. By unraveling the molecular changes at the cellular level induced by inflammation, researchers are paving the way for targeted interventions and treatments. The study's data, along with numerous other papers under the BRAIN Initiative, have been deposited in the Neuroscience Multi-Omic Archive (NeMO Archive). This curated genomic data repository enables researchers to delve deeper into the intricate workings of the brain, offering hope for the future development of effective therapies for neurodevelopmental disorders and related conditions like dementia, Parkinson's disease, and substance use disorders.
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