Scientists genetically engineer cocaine addiction-proof mice

Scientists from the University of British Columbia have genetically engineered several mice that are resistant to cocaine addiction.

By increasing the levels of a protein called cadherin in the mice, the scientists essentially prevented the pleasurable memory of cocaine from forming in the mice and leading to addiction.

The cadherin protein helps bind cells together and, in the brain, helps to strengthen synapses between neurons.

This strengthening of synapses is integral to learning, including forming the memory of the pleasure induced by stimulants, and thus led to the belief that the mice with increased cadherin would in fact be more susceptible to addiction.

Shernaz Bamji, a professor in the Department of Cellular and Physiological Sciences, and her colleagues injected cocaine into mice over several days and immediately placed them in a distinctly decorated compartment in a three-room cage. The notion was that the mice would associate the cocaine rush with that compartment and gravitate towards it.

After the cocaine treatment days, the mice were put in the cage and allowed to go where they wished. It was found, to the researchers’ surprise, that while the normal mice would always head to the cocaine-associated compartment, the cadherin boosted mice would spend only half as much time there.

The results indicated that the engineered mice hadn’t formed the strong memories of the drug that would be expected and, following brain tissue analysis, it was found that extra cadherin prevents a type of neurochemical receptor from migrating from the cell’s interior to the synaptic membrane. Without said receptor, neurons find it harder to receive signals from adjoining neurons and the synaptic memory of cocaine’s high thus does not “stick”.

“Through genetic engineering, we hard-wired in place the synapses in the reward circuits of these mice,” said graduate student Andrea Globa, a co-lead author with former graduate student Fergil Mills. “By preventing the synapses from strengthening, we prevented the mutant mice from ‘learning’ the memory of cocaine, and thus prevented them from becoming addicted.”

Video courtesy of University of British Columbia

The researchers’ findings go a long way towards explaining the findings of previous studies that showed people with substance abuse problems have more genetic mutations associated with cadherin and cell adhesion. Furthermore, the evidence that addiction is as much genetically predilected as a result of poor decision making could allow for prediction of vulnerability to drug abuse.

Unfortunately, there are still pitfalls ahead. While increasing cadherin in humans could help with a resistance to addiction, it could pose other risks. In many cases, it’s important to strengthen synapses – even in the reward circuit of the brain.

“For normal learning, we need to be able to both weaken and strengthen synapses,” Dr. Bamji says. “That plasticity allows for the pruning of some neural pathways and the formation of others, enabling the brain to adapt and to learn. Ideally, we would need to find a molecule that blocks formation of a memory of a drug-induced high, while not interfering with the ability to remember important things.”

Breakthrough prosthetic arm detects spinal nerve signals

A team of bioengineers have developed a prosthetic arm that is able to detect nerve signals in the spinal cord. By imagining they are controlling a phantom arm, patients create electrical signals in the spinal motor neurons that can be detected by the arm’s sensor technology and used as commands.

The robotic arm prosthetics currently available are controlled by the patient twitching the remnant muscles in their shoulder or arm. The technology in said arms is fairly basic and able to perform only or two grasping commands. Said limitations have led to a global 40-50% discard rate for such prosthetics.

The new prosthetic is potentially capable of far more commands due to its use of sensor technology. The research suggests that the signals sent by spinal motor neurons can be detected in much greater amounts than with remnant muscle fibre, meaning that the arm can ultimately be programmed with more commands to increase the functionality.

Image courtesy of Imperial College London

“When an arm is amputated the nerve fibres and muscles are also severed, which means that it is very difficult to get meaningful signals from them to operate a prosthetic,” said lead author Dr Farina, from the Department of Bioengineering at Imperial College London.

“We’ve tried a new approach, moving the focus from muscles to the nervous system. This means that our technology can detect and decode signals more clearly, opening up the possibility of robotic prosthetics that could be far more intuitive and useful for patients. It is a very exciting time to be in this field of research.”

The researchers experimented in the lab with six volunteers who were either amputees from the shoulder down or just above the elbow. Following physiotherapy training, all six were able to make a more extensive range of movements than would be possible using a classic muscle-controlled robotic prosthetic.

It is hoped that the breakthrough could significantly reduce the current 40-50% discard rate for prosthetic limbs

The volunteers underwent a surgical procedure at the Medical University of Vienna that involved re-routing parts of their Peripheral Nervous System (PNS), connected with hand and arm movements, to healthy muscles in their body. Depending on the type of amputation, this re-routing was either directed to the pectoral muscle in the chest or the bicep in the arm.

Researchers suggested that the current model is still subject to refinement, but could be on the market in the next three years.

The laboratory tests have taken them to the end of the proof of concept stage and they will now begin involve extensive clinical trials with a much wider cross section of volunteers in order to make the technology more robust.

Much of Dr Farina’s research was carried out while at the University Medical Centre Gottingen and research was conducted in conjunction with Dr Farina’s co-authors in Europe, Canada and the USA. The work was supported by the European Research Council, the Christian Doppler Research Foundation of the Austrian Federal Ministry of Science, Research and Economy and the European Union’s Horizon 2020 research and innovation programme.