A UCLA-led study comparing brain cells known as astrocytes in humans and mice found that mouse astrocytes are more resistant to oxidative stress, a harmful imbalance that is a mechanism behind many neurological disorders. Lack of oxygen triggers molecular repair mechanisms in these mouse astrocytes, but not in human astrocytes. In contrast, inflammation activates immune response genes in human astrocytes, but not mouse ones.
Although the mouse is a ubiquitous laboratory model used in research for neurological diseases, the results of studies in mice are not always applicable to humans. In fact, more than 90% of drug candidates who show a preclinical promise for neurological disorders eventually fail when tested in humans, in part because of a lack of knowledge about differences in astrocytes and others. brain cells between the two species.
Astrocytes are crucial for brain development and function and play an important role in neurological disorders that, however, are not fully understood. Injury or infection causes astrocytes to move from a state of rest to a reactive state in which they can help repair the brain, but they can also increase harmful inflammation.
The scientists studied developing cells purified from human and mouse brain tissue, as well as cells cultured in serum-free cultures from selected astrocytes using an antibody-based method developed by the corresponding author of the study.
This technique was necessary because the conventional method of selecting astrocytes by culturing them in serum — a mixture of proteins, hormones, fats, and minerals — throws them into a reactive state similar to that caused by infection or injury. With the researchers ’strategy, they were able to examine astrocytes in a healthy state and under controlled conditions of oxidative stress, lack of oxygen, and excessive inflammation.
The findings have implications for basic and translational research into neurological disorders such as Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis—Conditions whose underlying mechanisms are oxidative stress, lack of oxygen and excessive inflammation.
Because mouse astrocytes hold up oxidative stress rather, the authors suggest that laboratory models for neurodegeneration could be designed to decrease this resistance, making them more human. Also, the mouse astrocyteOxygen deficiency repair facilities may suggest a new route of stroke research. And neuroscientists can take a more informed approach to preclinical studies given the differences in response to inflammation between mouse and human astrocytes, as well as metabolic differences identified in the study.
The study is published online in the journal Communications on Nature.
Jiwen Li, a postdoctoral fellow at UCLA, is the first author of the study and the corresponding author is Ye Zhang, an assistant professor of psychiatry and bio-behavioral sciences at UCLA and a member of the Eli and Edythe Center for Regenerative Medicine. UCLA Stem Cell Research and UCLA Semel Institute for Neuroscience and Human Behavior. Other co-authors are Lin Pan, William Pembroke, Jessica Rexach, Marlesa Godoy, Michael Condro, Alvaro Alvarado, Mineli Harteni, Yen-Wei Chen, Linsey Stiles, Angela Chen, Ina Wanner, Xia Yang, Daniel Geschwind and Harley Kornblum, all of UCLA, and Steven Goldman of the University of Rochester and the University of Copenhagen.
Jiwen Li et al, Conservation and divergence of vulnerability and stress responses between human astrocytes and mice, Communications on Nature (2021). DOI: 10.1038 / s41467-021-24232-3
University of California, Los Angeles
Citation: Differences in Human Brain and Mouse Cells Have Important Implications for Disease Research (2021, June 25) Retrieved June 26, 2021 at https://medicalxpress.com/news/2021- 06-differences-human-mouse-brain-cells.html
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