Everyone has a knowledge hungry science-worm in them that awakens every time they read about a ground-breaking, earth-shattering, neuron-exploding discovery. Even more so when they come across vaccines, drugs, and therapies that have borne the brunt of pre-clinical testing and finally moved on to clinical trials, a step closer to the general public. Unfortunately, many a time they come across dismal updates about drug failures during human trials. In 2013, Cogane, a drug for Parkinson’s disease, failed to show any significant clinical effects in humans after being declared successful in animal testing. Why these drugs fail is a scientific dilemma of epic proportions. The answer, Trygve Bakken believes, lies in a simple fact.
“Our brains are not just enlarged mouse brains.”
A New Brain Cell
In 2018, two teams of neuroscientists offered some insights into neurophysiology through their discovery of a neuron unique to human brains. The new finding was the result of a collaboration between the Allen Institute for Brain Science in the US and the University of Szeged in Hungary. Both teams identified the distinctive-looking neurons independently; however, several years back Dr. Gábor Tamás from the University of Szeged, Hungary presented his research on neuron types at the Allen Institute. When both teams realized they were working to map the same neuron, they decided to collaborate. The neuron has been named “the rosehip” after its rosebush-like structure as described by the lead scientist of the research, Trygve Bakken. Not only is the neuron itself unique to humans but its structure is also different from other neurons in the human brain. When the researchers at the Allen Institute analysed the genes of the rosehip neuron in post-mortem tissue from two deceased donors, they found that the neurons acted differently. The rosehip neurons expressed genes never documented in mouse neurons. The finding could potentially help in explaining drug failure during human trials.
Role in Neurophysiology
The brain is a complex organ, with an intricate mesh of neurons — much like a coiled-up spider web with each thread leading to the core. The human brain, in particular, is the most complex structure in the entire animal kingdom. In comparison with mice, our genetically closest members of the animal kingdom, the human brain possesses a much larger cortex with a good deal of neuron density. Neurons in the cortex are specialized for two functions: excitatory neurons send and receive nerve impulses while inhibitory neurons stop excitatory neurons from firing. Rosehip neurons belong to the latter type: they curb electrical impulses from passing to the next neuron. “They can really act as a sort of brake on the system,” says Ed Lein, an investigator at the Allen Institute for Brain Science.
Proving the Uniqueness of the Rosehip
In the quest to prove the uniqueness of the rosehip, Bakken’s team cross-analysed gene expression profiles of human and mouse cortex. A gene expression profile is basically a report that tells you which genes are active in which part of the cell or organ. This largely determines what is going on in the cell or what functions the cell performs.
“There are a number of genes that are turned on just in that cell and not in other[s],” Bakken said.
This expression profiling has been an important step in figuring out why drugs and therapies, especially those for psychiatric or neural diseases, fail in human trials. Discovery of the rosehip lays a foundation that we might have to dive deeper into therapies, exclusively tailored and tested for humans. The team’s next endeavor is to examine the physiology and anatomy of rosehip neurons in patients with neuropsychiatric disorders.
Photographing the Rosehip
The research team in Hungary applied various brain mapping techniques to study the electrical activity and shapes of neurons in brain tissue that had been removed from people’s brains during surgery. Brain mapping is a complex but traditional technique that involves filling the cells with a special dye and recording their response to different electrical signals. A special software then recreates the image of the neuron or neural circuit using the signals it receives. Comparing the images with those from mouse brains led to an interesting revelation: neither the brain mapping nor the expression profiles revealed any links to mouse brains.
“It’s too early to say that this is a completely unique cell type because we haven’t looked in other species yet,” adds Lein. “But it really highlights the fact that we need to be careful about assuming that the human brain is just a scaled-up version of a mouse.”