Psychiatric drugs meant for humans have been tested on mice for years. The two species’ brains have similar cellular structures. But a new study by the Seattle-based Allen Institute for Brain Science shows there are also significant differences.
Findings from the study, published Wednesday in the journal Nature, could affect how researchers develop medications for people with psychiatric disorders and devise treatments for brain diseases. The findings also help explain how assumptions about treating the human brain have led to a high rate of drug-trial failures, said Ed Lein, an investigator at the Allen Institute and the study’s lead author.
As part of the study, researchers assembled a list of the brain’s parts and produced a detailed comparison between the types of human and mouse brain cells.
“We finally have a way of quantitatively defining the types of cells that make up very complex brain regions,” Lein said. “Once we are able to do that, then we are able to start to understand how well animal models that we want to use to help study disease and develop new therapeutics are actually similar to the human, which is often a difficult question to answer.”
The parts list of the human brain can be used the way someone might use a list of parts to fix an appliance or an electronic gadget by looking at what each part does and how those parts work with the software.
“The brain is a very complex circuit, consisting of many, many different types of neurons and the cells that support them,” Lein said. “What we are doing is to try and deconstruct the human brain into its components.”
The institute published a study of the mouse brain last year. Comparing it with this new study helped illuminate the many differences between human and mouse brains. For example, while they share the same type of cells, those cells appear in different volumes, and components of the cells, such as serotonin receptors, have evolved differently in each species.
Understanding these differences down to the molecular and functional levels is valuable for researchers, said Nick Spitzer, a neuroscientist at the University of California San Diego, who was not involved with the study.
“This will save researchers time and money and provide a shield against misinterpretation of results,” he said. “I expect that the comparison between brains of mice and humans will be useful for our work on neurotransmitter switching.”
The study focused on a part of the human brain’s temporal lobe called the medial temporal gyrus. Most of the brains used were donated after a person’s death, but some live samples were procured from the surgeries of epilepsy patients.
This study and others from the Allen Institute are open for researchers anywhere to use. Having the study available and continuing to expand the project to the entire brain is critical to developing better treatments, Dr. Joshua Gordon, Director of the National Institute of Mental Health, said in a statement. The National Institutes of Health provided funding for the study.
“The ultimate impact of this understanding will be better treatments for mental illnesses,” Gordon said.
The next step for researchers and investigators at the Allen Institute is to continue examining other parts of the human brain and extend comparisons beyond mice to nonhuman primates. Humans are 75 million years removed from the closest relative we share with mice. The evolutionary distance is much closer between humans and our primate relatives that have more similar brains, Lein said.
The Allen Institute was founded by philanthropist and Microsoft co-founder Paul G. Allen to deeply explore human biology with a focus on the brain, cells and the immune system. The brain-science division was established in 2003. Allen died in October 2018.