Zinc plays important role in brain circuitry

November 22, 2006

To the multitude of substances that regulate neuronal signaling in the brain and spinal cord add a new key player: zinc. By engineering a mouse with a mutation affecting a neuronal zinc target, researchers have demonstrated a central role for zinc in modulating signaling among the neurons. Significantly, they found the mutant mouse shows the same exaggerated response to noise as children with the genetic disorder called "startle disease," or hyperekplexia.

The findings shed light on a nagging mystery in neurobiology: why the connections among certain types of neurons contain considerable pools of free zinc ions. And even though many studies had shown that zinc can act toxically on transmission of neural impulses, half a century of experiment researchers had not been able to show conclusively that the metal plays a role in normal nerve cell transmission.

However, in an article in the November 22, 2006, issue of the journal Neuron, published by Cell Press, Heinrich Betz and colleagues conclusively demonstrate just such a role for zinc.

In their experiments, the researchers produced mice harboring a mutant form of a gene for a receptor for zinc in neurons--thereby compromising the neurons' ability to respond to zinc. The mutation in the receptor, called the glycine receptor, targets the same receptor known to be mutated in humans with hyperekplexia. The receptor functions as a modulator of neurons in both motor and sensory signaling pathways in the brain and spinal cord.

The genetic approach used by the researchers was a more targeted technique than previous experiments in which researchers reduced overall neuronal zinc levels using chemicals called chelators that soak up zinc ions.

The resulting mutant mice showed tremors, delayed ability to right themselves when turned over, abnormal gait, altered transmission of visual signals, and an enhanced startle response to sudden noise.

Electrophysiological studies of the mutant animals' brain and spinal neurons showed significant zinc-related abnormalities in transmission of signals at the connections, called synapses, among neurons.

Betz and his colleagues wrote that "The data presented in our paper disclose a pivotal role of ambient synaptic [zinc ion] for glycinergic neurotransmission in the context of normal animal behavior." They also concluded that their results implied that manipulating synaptic zinc levels could affect the neuronal action of zinc, but that such manipulation "highlights the complexity of potential therapeutic interventions," which could cause an imbalance between the excitatory and inhibitory circuitry in the central nervous system.

In a preview of the paper in the same issue of Neuron, Alan R. Kay, Jacques Neyton, and Pierre Paoletti wrote "Undoubtedly this work is important, since it directly demonstrates that zinc acts as an endogenous modulator of synaptic transmission." They wrote that the findings "will certainly revive the flagging hopes of zincologists. This work provides a clear demonstration that interfering with zinc modulation of a synaptic pathway leads to a significant alteration in the phenotype of the animal." The three scientists added that the finding "puts a nice dent in the zinc armor, which held firm for more than 50 years."

Source: Cell Press

Explore further: Detailed images of NMDA receptors help explain how zinc and a drug affect their function

Related Stories

Here's how your body transports zinc to protect your health

November 3, 2016

Zinc is essential for wound healing, for vision, for DNA creation, for our senses of taste and smell, even for sexual health. But despite its importance, scientists have never fully understood the mechanism that moves the ...

The long-sought cure to Huntington's disease

September 15, 2016

The current lack of a treatment proven effective against 'Huntington's disease' (HD) is leaving one in every 10 000 people with psychiatric, movement, feeding and communication problems that are very difficult to live with. ...

Recommended for you

Artificial beta cells

December 8, 2016

Researchers led by ETH Professor Martin Fussenegger at the Department of Biosystems Science and Engineering (D-BSSE) in Basel have produced artificial beta cells using a straightforward engineering approach.

Key regulator of bone development identified

December 8, 2016

Loss of a key protein leads to defects in skeletal development including reduced bone density and a shortening of the fingers and toes—a condition known as brachydactyly. The discovery was made by researchers at Penn State ...

Researchers question lifelong immunity to toxoplasmosis

December 8, 2016

Medical students are taught that once infected with Toxoplasma gondii—the "cat parasite"—then you're protected from reinfection for the rest of your life. This dogma should be questioned, argue researchers in an Opinion ...

TET proteins drive early neurogenesis

December 7, 2016

The fate of stem cells is determined by series of choices that sequentially narrow their available options until stem cells' offspring have found their station and purpose in the body. Their decisions are guided in part by ...

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.