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THE LANCET Neurology Vol 1 June 2002 http://neurology.thelancet.com 79

Newsdesk

The human brain may be much more“evolved” than was previously thought,according to a new genetic study. Thefindings strengthen suspicions thatrapid, recent genetic change in Homosapiens could be to blame for oursusceptibility to Alzheimer’s and otherneurodegenerative diseases.

Famously, chimps and humanbeings are only 1% different in theirgenomes; this has left researchersstruggling to explain the obviousmental differences. But now acollaboration of German, US, andDutch scientists, led by Svante Pääbo ofthe Max Planck Institute forEvolutionary Anthropology in Leipzig,Germany, have used “gene chip”microarrays to show that the actualpattern of gene expression—the so-called transcriptome—has shifteddramatically (Science 2002; 296:340–43). Team member Ajit Varki(University of California at San Diego,CA, USA) summed it up as “sameingredients; different recipe”.

The experiment compared mRNAtranscription activity in postmortembrain, liver, and blood samples takenfrom adult humans, chimpanzees, andrhesus monkeys. Electrophoresis was

also used to check the actual proteinspresent in the neural tissue. The resultsshowed that, as expected, chimps andhuman beings were quite similar in thegenes that are “switched on” in theblood and liver. But the brain tissuesamples taken from frontal cortex

revealed that humans have a markedlydifferent pattern of genome activity—the result of a five-fold increase in theaccumulation of gene expressionchanges. Protein assays confirmed thatalthough chimpanzee brains employsimilar proteins, as their almost ident-ical genome would predict, the actuallevels of each protein differ significantly.

Varki says this is good evidence thatthe human brain has been subject to

swift evolutionary change, adding that itwould only take relatively smallalterations in genome expression duringneurodevelopment to produce bigdifferences in the structures that result.“What we are seeing is probably thecontinuing fingerprint of those earlychanges,” he said.

Patrick Hof (Mount Sinai School ofMedicine, New York, USA) called theresults “thrilling” because they promisea new way of getting at brain diseasespeculiar to human beings. “Somebelieve a heightened vulnerability mayhave been the price we paid for rapidevolutionary change to the brain be-cause there are a plethora of disordersthat seem unique to humans, especiallyage-related ones like Alzheimer’s. In oldchimps, we find no sign of neuro-fibrillary tangles or shrinkage in thehippocampus. Schizophrenia, autism,and multiple sclerosis also look likeexclusively human diseases. With noobvious genetic differences, it was hardto say why the ape brain was protected.But this work could allow us to isolatethe different pattern of proteins beingexpressed and that may give us some bigclues”, says Hof.John McCrone

An evolutionary root for Alzheimer’s disease?

Same ingredients—different recipe?

Remote possibility of sensory prostheses

First came monkeys that moved robotarms with neural signals sent via theinternet, next similarly “wired-up”monkeys seemed to learn to move acursor by thought alone. But the lateststep in the field focuses on the receptionof virtual sensory signals, and has alsojumped species. The unanticipatedoutcome of this research, which aimsultimately to assist paralysed peopleregain function, is the birth of remote-controlled rats.

The underlying reason for a studythat sounds like science fiction is thedevelopment of neurorobotics, explainsfirst author Sanjiv Talwar (StateUniversity of New York, NY, USA). Histeam has “previously shown that it maybe feasible for paralysed patients tocontrol artificial limbs by thought. Itwould be useful if we could implementsensory feedback from the devices

themselves so that someday patientsmay perhaps even be able to experiencetouch and proprioception when using aprosthesis.” He suggests that a “sensoryprosthesis” could improve limbcontrol. “In this study, we wanted toinvestigate just how much controlbrain-stimulation sensory cues couldexert over behaviour.”

He is asking whether the brain—inthis case a rat brain—can be artificiallyand remotely “controlled”. To test thisin practice, the team implanted micro-electrodes into the brain and whiskersof five rats. Brain microstimulation wasdelivered via a microprocessor—wornby the rats in a backpack—into areas ofthe somatosensory cortex that processsensory cues from whiskers and themedial forebrain bundle, which med-iates reward. The researchers then useda simple regime of directional signals

reinforced with rewards to guide therats remotely in complex navigationaltasks. On average, the rats moved at1 km/h over a test period lasting 1 hour(Nature 2002; 417: 37–38).

“It so happened that we found thatseemingly complex behaviours, such asguided navigation, can easily be cond-itioned using virtual learningmethods”, says Talwar. Although theteam has no further plans to developthis experiment any further, hespeculates that “almost all behavioursthat may require studies in freelyroaming animals could be conditionedin this way”. In addition, “the ability toreceive brain sensory activity remotelyand interpret it accurately could allow aguided rat to function as both a mobilerobot and a biological sensor”, theresearchers note.Kelly Morris