"Nature" publishes research on gene expression map of prefrontal cortex, revealing brain development and disease mechanisms

China News Service, Beijing, September 24 (Reporter Sun Zifa) The international academic journal "Nature" and its series of journals have recently published a number of neuroscience papers, using the largest known gene expression map of the human prefrontal cortex brain region to help explore development, aging, degeneration and disease.

Nature and its series of journal papers analyzed more than 6.3 million gene expression profiles from the brains of 1,494 deceased donors to the US PsychAD project. These studies further elucidate the development of brain regions in the prefrontal cortex at different stages of life and may be used to study aging, cognitive decline and disease susceptibility.

Schematic diagram of the results of this series of research. Photo courtesy Springer Nature

According to the PsychAD project cooperation team, research has found that the human brain undergoes tremendous developmental changes in early life and late adulthood, and these changes affect cognitive abilities, behavior, and disease susceptibility. Analyzing gene expression patterns at different stages of life may provide insights into how the brain transforms, which could be used to study normal aging as well as the development of neurodegenerative and neuropsychiatric disorders.

The prefrontal cortex brain region is involved in key cognitive functions (such as problem solving, planning, and emotion regulation) and is sensitive to age-related degeneration. It is an ideal brain region worthy of study and is also a research target of the PsychAD project to investigate diseases such as Alzheimer's disease.

Among the latest papers published by the PsychAD collaboration group, three were published in the main journal of Nature. The first paper describes the largest population-scale single-cell transcriptome map of the human dorsolateral prefrontal cortex reported so far. The authors evaluated 1.3 million gene expression profiles from 284 neurotypical donors ranging in age from infancy to late adulthood to provide evidence of how gene expression changes over time.

These changes correspond to brain remodeling in early development, stabilization in midlife (until about age 24), structural degradation after age 24, and cellular reprogramming after age 65. The authors also identified changes in gene expression associated with neuronal toughness in early life and neuronal vulnerability later in life.

The second paper reports on a map of gene expression changes associated with brain disease. The authors evaluated the complete PsychAD data set (6.3 million gene expression profiles from 1,494 donors), which includes not only neurotypical individuals, but also individuals with brain diseases such as Alzheimer's disease and other forms of dementia, Parkinson's disease, schizophrenia, and bipolar disorder.

Regardless of the disease being studied, there are certain similarities in the expression of genes related to basic cell functions. However, the similarities in gene expression changes between different forms of dementia and Parkinson's disease increased significantly, especially in genes involved in neuronal development and synaptic function.

The third paper maps how genetic risk for brain disease affects specific cell types in different people of European, African and American descent. The authors reveal thousands of previously unknown gene-trait associations and discover conserved cell type-specific mechanisms. They believe the findings could help provide a deeper understanding of the mechanisms behind neuropsychiatric and neurodegenerative diseases.

"Nature" published a "News and Views" article by peer experts at the same time. It was believed that the results published by the PsychAD project provide research resources for understanding health changes and disease-related changes in the prefrontal cortex, and are expected to promote the discovery of genes related to neuropsychiatric, neurodegenerative, behavioral, cognitive and emotional traits.

The PsychAD collaboration group will publish several more papers in Nature Medicine, Nature Genetics, and Nature Communications.

It is reported that the PsychAD project is a large-scale international research project funded by the National Institutes of Health and led by the Icahn School of Medicine at Mount Sinai and other institutions. It aims to deeply explore the molecular and cellular mechanisms of Alzheimer's disease (AD) and related neurodegenerative and neuropsychiatric diseases. (over)