Dawn of the Planet of the… Mice?
By Ronan Talty, Behavioral Neuroscience, 2017
Every thought, action, memory, feeling, and experience that you perform or possess is the result of your brain. At the root of all of those phenomena, are the brain’s most fundamental cells: neurons and glial cells. Neurons are the brain’s functional cells that convey electrochemical ‘messages’ to different body regions. These ‘messages’ can invoke a variety of responses including sensory perceptions and motor action.
Astrocytes, a particular type of glial cell, offer biochemical support to neurons, guide their development, and dictate their repair. Humans wield astrocytes two and a half times larger than rodents and other animals, and it is widely believed that this discrepancy gives rise to the increased signal speed and processing power evident in human brains.
Recently, Steve Goldman and his laboratory team at the University of Rochester Medical Center in New York published the results of their fascinating experiment that sought to create mice with human astrocytes.
Goldman and his group investigate translational medicine. The goal of their research is to accelerate our knowledge of human brain diseases by studying them in animals, or in vivo, rather than on petri dishes.
In their previous work, the group developed efficient methods used to identify and isolate human glial progenitor cells (human astrocyte precursors) in quantities and purities appropriate for transplantation. The scientists aimed to utilize this capability and test the implantation of such cells in mice.
To begin, the group collected and isolated the human glial progenitor cells from donated second trimester human fetuses. They then inserted 300,000 of the cells dispersed over five injection sites into each mouse pup. Injection results were periodically measured throughout the experiment’s length via histology and immunolabeling.
These techniques combine anatomical, immunological, and biochemical techniques to identify discrete tissue components by the interaction of target antigens with specific antibodies tagged with a visual label.
After nine months, analysis revealed that the injected precursor cells experienced such a competitive advantage over their endogenous mouse counterparts that they had replaced virtually all of them.
Subsequent learning tests uncovered enormous intellectual consequences of the injected human cells. In one situation, the mice underwent fear conditioning and extinction protocol, a behavioral paradigm used to study fear retention in a laboratory setting.
On average, the ‘human’ mice displayed four times more freezing than the control mice, indicating a substantially stronger memory for the conditioned fear. This result added to a variety of other learning tasks’ results led the group to label the mice with “increased synaptic plasticity and improved cognitive performance.”
Although it will take time for science to completely exploit the results of this experiment, the long-term benefits will undoubtedly be staggering. Goldman and his lab contend that, “These human glial chimeric mice should permit us to define the specific contributions of glia to a broad variety of neurological disorders, using human cells in vivo.”
Discovering the molecular basis for the competitive dominance of the human cells and the development of disease-specific mice with relevant glial cell dysfunctions represent only the most apparent ways which this research might aid the advancement of treatments for neurodegenerative and neuropsychiatric disorders.
Looking forward, Goldman hopes to expand the experiment to rats in the next year and a half. He also quelled all fears of a mouse-earth takeover in stating that, “this does not provide the animals with any capabilities that could any way be ascribed as human” and that each injected animal is “still a mouse.”
