Copper on the brain

May 27, 2013 by Ynn Yarris
Copper Sensor-3 (CS3), a small-molecule fluorescent probe, was used to map the movement of copper in the brain triggered by neuronal activity.

(Medical Xpress)—The value of copper has risen dramatically in the 21st century as many a thief can tell you, but in addition to the thermal and electrical properties that make it such a hot commodity metal, copper has chemical properties that make it essential to a healthy brain. Working at the interface of chemistry and neuroscience, Berkeley Lab chemist Christopher Chang and his research group at UC Berkeley have developed a series of fluorescent probes for molecular imaging of copper in the brain. Speaking at the recent national meeting of the American Chemical Society in New Orleans, he described the challenges of creating and applying live-cell and live-animal copper imaging probes and explained the importance of meeting these challenges.

"The is a unique , possessing unparalleled in a compact space," Chang said. "Although it accounts for only two-percent of total body mass, it consumes 20-percent of the oxygen taken in through respiration. As a consequence of its high demand for oxygen and oxidative metabolism, the brain has among the highest levels of copper, as well as iron and zinc in the body."

Neuron and in the brain both require copper for the basic respiratory and cytochrome c oxidase and superoxide dismutase. Copper is also necessary for brain-specific enzymes that control neurotransmitters, such as dopamine, as well as neuropeptides and dietary amines. Disruption of copper oxidation in the brain has been linked to several , including Alzheimer's, Parkinson's, Menkes' and Wilson's.

"The complex relationships between copper status and various stages of health and disease have been difficult to determine in part because of a lack of methods for monitoring dynamic changes in copper pools in whole ," Chang said. "We've been designing fluorescent probes that can map the movement of copper in live cells, tissue or even model organisms, such as mice and zebrafish."

Their first success was Coppersensor-3 (CS3), a small-molecule fluorescent probe that can be used to image labile copper pools in living cells at endogenous, basal levels. They used CS3 in conjunction with synchrotron-based X-ray fluorescence microscopy (XRFM) to discover that neuronal cells move significant pools of copper upon activation and that these copper movements are dependent on calcium signaling.

"This was the first established link between mobile copper and major cell signaling pathways," Chang said. "Being able to map transient copper movements after neuronal depolarization revealed how neural activity triggers copper mobility, and enabled us to create a model for calcium/copper crosstalk in neurons."

The CS3 probe was followed by Mitochondrial Coppersensor-1 (Mito-CS1), a fluorescent sensor that can selectively target mitochondria and detect basal and labile copper pools in living cells. Mitochondria, the organelles that generate most of the chemical energy used by cells, are important reservoirs for copper. By allowing direct, real-time visualization of exchangeable mitochondrial copper pools, the Mito-CS1 probe enabled Chang and his colleagues to discover that cells maintain copper homeostasis in mitochondria even in situations of copper deficiency and metabolic malfunctions.

"This work illustrated the importance of regulating copper stores in mitochondria," Chang said.

The latest copper probe from Chang's group is Coppersensor 790 (CS790), a fluorescent sensor that features near-infrared excitation and emission capabilities, ideal for penetrating thicker biological specimens. CS790 can be used to monitor fluctuations in exchangeable copper stores under basal conditions, as well as under copper overload or deficiency conditions. Chang and his group are using CS790 to study a mouse model of Wilson's disease, a genetic disorder characterized by an accumulation of excess copper.

"The in vivo fluorescence detection of copper provided by CS790 and our other fluorescent probes is opening up unique opportunities to explore the roles that copper plays in the healthy physiology of the brain, as well as in the development and progression -related diseases," Chang said.

Explore further: Metal binding important for metformin action

Related Stories

Metal binding important for metformin action

April 14, 2012
(HealthDay) -- The ability of metformin to bind mitochondrial copper may be essential to its mechanism of action, according to a study published online April 9 in Diabetes.

Discovery helps explain how children develop rare, fatal disease

April 30, 2013
One of 100,000 children is born with Menkes disease, a genetic disorder that affects the body's ability to properly absorb copper from food and leads to neurodegeneration, seizures, impaired movement, stunted growth and, ...

Recommended for you

Scientists discover common obesity and diabetes drug reduces rise in brain pressure

August 23, 2017
Research led by the University of Birmingham, published today in Science Translational Medicine, has discovered that a drug commonly used to treat patients with either obesity or Type II diabetes could be used as a novel ...

Use of brain-computer interface, virtual avatar could help people with gait disabilities

August 23, 2017
Researchers from the University of Houston have shown for the first time that the use of a brain-computer interface augmented with a virtual walking avatar can control gait, suggesting the protocol may help patients recover ...

Researcher working to develop new tool for non-invasive neuromodulation of human brain

August 23, 2017
A UTA researcher is developing a technology that will map and image the effects of infrared light shone on the human brain that may be able to modulate and improve brain waves and circuits at certain spots in the brain.

Physicist reports binary marker of preclinical and clinical Alzheimer's disease

August 23, 2017
A new technique shows high potential for providing a discrete, non-invasive biomarker of Alzheimer's disease (AD) at the individual level during both preclinical and clinical stages. The proposed biomarker has a large effect ...

Firing of neurons changes the cells that insulate them

August 22, 2017
Through their pattern of firing, neurons influence the behavior of the cells that upon maturation will provide insulation of neuronal axons, according to a new study publishing 22 August in the open access journal PLOS Biology ...

Activating brain region creates intense desire to use cocaine

August 22, 2017
Researchers have identified a portion of the brain that intensifies one's desire for certain rewards—in this case, mimicking addiction to cocaine.

0 comments

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.