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."
Heidi Hardman | EurekAlert!
A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital
Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...
Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.
A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
21.04.2017 | Physics and Astronomy
21.04.2017 | Health and Medicine
21.04.2017 | Physics and Astronomy