“Man had always assumed that he was more intelligent than dolphins because he had achieved so much — the wheel, New York, wars and so on — whilst all the dolphins had ever done was muck about in the water having a good time. But conversely, the dolphins had always believed that they were far more intelligent than man — for precisely the same reasons….In fact there was only one species on the planet more intelligent than dolphins, and they spent a lot of their time in behavioural research laboratories running round inside wheels and conducting frighteningly elegant and subtle experiments on man. The fact that once again man completely misinterpreted this relationship was entirely according to these creatures’ plans.” – Douglas Adams, The Hitchhiker’s Guide to the Galaxy

As tempting as it may be to believe the science fiction version of the intelligence rankings, real-life science has spoken and suggests (much to my displeasure) that humans may actually be the highest on the intelligence scale.

Glia are non-neuronal cells found in the brain mainly described as performing “housekeeping” functions, for example, providing structural support to neurons, and providing them with nutrients. Astrocytes are a specific type of glia, and as one might hypothesize, they are bigger in humans than in mice. Was this just a consequence of humans having more complex brains, or do these astrocytes have different functions in humans beyond the basic housekeeping functions? To test this, scientists grafted human astrocyte progenitor cells into developing mouse brains to create chimeric mice.

Human astrocyte (green) and mouse astrocyte (red)

The human astrocytes that matured successfully matured as human cells; characteristics such as their size were unaffected by being in a mouse environment. But they did not remain completely foreign – they successfully formed electrical connections with the mouse cells. Their differing cellular properties were thus propagated into the mouse neural networks. Of particular interest is the hippocampus, the brain region important for learning and memory. Chimeric hippocampal slices had a higher level of baseline excitatory activity, and long-term potentiation (LTP), or synapse strengthening, was much greater. At the molecular level, this can be explained because the human cells express higher levels of a protein that promotes an increased number of glutamate receptors at the synapse.

There were also clear differences in the behavior of chimeric mice. Experiments were performed to test learning and memory abilities to corroborate the cellular results observed in the hippocampus. A classic fear conditioning experiment involves pairing a tone with a foot shock; mice learn to associate the two and exhibit freezing behavior after hearing a tone. Chimeras learned the association after only one tone/shock pairing. The learning persisted for several days, during which time control animals did not learn the initial association. The experiment was repeated as context fear conditioning, meaning that the mice were placed in different chambers that had varying floors and odors. Chimeric mice were able to differentiate between chambers significantly better than their control counterparts. In other learning and memory tasks, these mice learned their way through mazes faster and were better at familiar object recognition in novel contexts.

The results of this study show that glial cells have much more function beyond their basic housekeeping properties. A single cell graft manipulation was enough to significantly improve mouse performance on learning and memory tasks. Complexity of these cells has evolved with the brain, and this provides important new insight on how exactly this complexity has come to be. Future experiments could involve grafting chimpanzee or macaque glia, any differences observed could be key in outlining how our processing abilities evolved from our monkey fathers (I additionally support research with dolphin glia grafts, keeping on the theme of the three most intelligent species). Unfortunately, without the higher processing abilities made possible by human cells, mice likely cannot achieve the tasks and level of status they exhibit in the science fiction. It seems as though man has indeed correctly interpreted his relationship with the mouse.

So long, and thanks for all the fish.

-Reena Clements

References:

Human Brain Cells Boost Mouse Memory – ScienceNOW

Forebrain Engraftment by Human Glial Progenitor Cells Enhances Synaptic Plasticity and Learning in Adult Mice – Cell Stem Cell

August 25, 2009 marked the day that America, and most importantly Massachusetts, lost one of its greatest senators, Ted Kennedy. Kennedy was diagnosed with a type of brain cancer called glioblastoma multiforme (GBM) in May 2008 after suffering from a seizure. GBM is a tumor formed in the glial, or supportive, brain cells; there is no current evidence for a genetic predisposition to this type of cancer. The American Cancer Society believes that 21,000 Americans are diagnosed with brain tumors, and about 10,000 are GBMs. They are the most aggressive and common type of brain tumor, which are resistant to many types of treatments. Only 3% of patients diagnosed with these tumors generally survive five years after diagnosis.

Almost two years after Kennedy’s death, doctors are using the drug Avastin to treat GMBs. Avastin blocks the growth of new blood vessels, a necessary component for the survival of tumors. In one study conducted on Dennis Sugrue, physicians thread a fine tube through his blood vessels and into his head to spray the drug on the location where the tumor had been cut out. They did this experiment because the tumor began growing back even after treatment with surgery, radiation, and chemotherapy. The FDA has approved the use of this drug on GMB, based on the results of 2 phase II clinical trials that showed reduced tumor size in the patients, but it can only be administered after a prior treatment is performed on the tumor.

One of the biggest challenges facing the treatment of GBM is the blood-brain barrier, a separation of the circulating blood and the brain’s extracellular fluid. It occurs along the capillaries and prevents the diffusion of many cells into the brain. Dr. John Boockvar, a brain surgeon at New York-Presbyterian/Weill Cornell, is administering the Avastin to Mr. Sugrue by first injecting mannitol, a drug that opens the blood-brain barrier, and then flooding the tumor with the drug. In the future, other drugs may be combined with Avastin to combat GBM. Although it is unknown whether it improves disease-related symptoms or survival in people under this treatment, it is promising.  Mr. Sugrue’s tumor has decreased in size and his treatment is still an ongoing process.

Although the survival rate for GBM is very low, it is unfortunately the reason why there is a push to try more treatments and expand experimental trials. One can only hope that this treatment leads to more breakthroughs, and more patients like Mr. Sugrue will be able to live longer, healthier lives.