Boosting supply of key brain chemical reduces fatigue in mice

December 20, 2010

Researchers at Vanderbilt University have "engineered" a mouse that can run on a treadmill twice as long as a normal mouse by increasing its supply of acetylcholine, the neurotransmitter essential for muscle contraction.

The finding, reported this month in the journal Neuroscience, could lead to new treatments for neuromuscular disorders such as myasthenia gravis, which occurs when cholinergic nerve signals fail to reach the muscles, said Randy Blakely, Ph.D., director of the Vanderbilt Center for Molecular Neuroscience.

Blakely and his colleagues inserted a gene into that increased the production of a protein called the choline transporter at the neuromuscular junction.

The choline transporter is vital to the capacity for – including the ability to breathe – because it regulates the supply of choline, the precursor to acetylcholine. "We reasoned that giving more of this might enhance muscle function and reduce nerve-dependent fatigue," Blakely said.

Other researchers have manipulated the gene for the muscle tissue growth factor myostatin to produce animals with greater strength and endurance, but Blakely said this may be the first time "neural endurance" was enhanced by manipulating the nerves that innervate .

Drugs that increase choline transporter activity "could represent a novel therapeutic strategy" for myasthenia gravis and a wide range of other disorders that involve cholinergic signaling deficits, Blakely said.

These disorders include muscular dystrophy, congestive heart failure, depression, schizophrenia, Alzheimer's disease and attention-deficit hyperactivity disorder (ADHD). "The brain uses acetylcholine for a wide variety of functions, including the ability to sustain attention," Blakely noted.

Last year, Blakely and his colleagues reported that a variation in the choline transporter gene is associated with the "combined" type of ADHD, which is characterized by both inattention and hyperactivity/impulsivity.

Explore further: 'Mighty mice' made mightier

Related Stories

'Mighty mice' made mightier

August 29, 2007

The Johns Hopkins scientist who first showed that the absence of the protein myostatin leads to oversized muscles in mice and men has now found a second protein, follistatin, whose overproduction in mice lacking myostatin ...

Sticky blood protein yields clues to autism

March 4, 2008

Many children with autism have elevated blood levels of serotonin – a chemical with strong links to mood and anxiety. But what relevance this “hyperserotonemia” has for autism has remained a mystery.

Protein on 'speed' linked to ADHD

July 8, 2008

A genetic change in the dopamine transporter – one of the brain's dopamine-handling proteins – makes it behave as if amphetamine is present and "run backward," Vanderbilt University Medical Center investigators report ...

Researchers iron out new role for serotonin

January 27, 2009

Vanderbilt University Medical Center investigators have found a surprising link between brain iron levels and serotonin, a neurotransmitter involved in neuropsychiatric conditions ranging from autism to major depression.

More choline reduces Down syndrome dysfunction

June 2, 2010

( -- In a mouse model of Down syndrome, pregnant and lactating mice that received additional choline had offspring that fared much better than those whose mothers did not receive choline, a new study finds.

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.