Category: Alzheimer’s

The unexpected survival of embryonic neurons transplanted into the brains of newborn mice in a series of experiments at the University of California, San Francisco (UCSF) raises hope for the possibility of using neuronal transplantation to treat diseases like Alzheimer's, epilepsy, Huntington's, Parkinson's and schizophrenia.

 

The experiments, described this week in the journal Nature, were not designed to test whether embryonic neuron transplants could effectively treat any specific disease. But they provide a proof-of-principle that GABA-secreting interneurons, a type of brain cell linked to many different neurological disorders, can be added in significant numbers into the brain and can survive without affecting the population of endogenous interneurons.

The survival of these cells after transplantation in numbers far greater than expected came as a shock to the team, which was led by UCSF professor Arturo Alvarez-Buylla, PhD, and former UCSF graduate student Derek Southwell, MD, PhD.

The prevailing theory held that the survival of developing neurons is something like a game of musical chairs. The brain has limited capacity for these cells, forcing them to compete with each other for the few available slots. Only those that find a place to "sit" (and receive survival signals derived from other cell types) will survive when the music stops. The rest die a withering death.

Based on this theory, the UCSF team had expected only a fixed and small number of transplanted embryonic interneurons would survive in the brains of older recipient mice, regardless of how many they transplanted. What they found was very different: Regardless of how many they transplanted, a consistent percentage always survived.

"[This constant rate of survival] suggests that these cells, which other collaborative studies have shown have great therapeutic promise, can be added to cortex in significant numbers," said Alvarez-Buylla, who is the Heather and Melanie Muss Professor of Neurological Surgery and a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

Past work at UCSF and elsewhere has shown that transplanting these cells can create a new critical period of plasticity in the recipient brain, reduce seizures in animal models of epilepsy, and reduce Parkinson's-like movement disorders in laboratory rats. The activity of these cells is often disrupted in Alzheimer's disease, and their number is altered in the brains of people with schizophrenia. When transplanted into the spinal cord, they also help decrease pain sensation.

In the current study, the UCSF team found that as they altered the number of cells they transplanted, a constant proportion of these cells survived — rather than a constant number — suggesting that a fraction of the cells is destined to die by cell-autonomous mechanisms or that a survival factor is secreted by the inhibitory neurons themselves. The work shows that these interneurons may be transplanted in far greater numbers than previously thought — an observation that could have important implications for the use of these cells to correct defects in the excitatory/inhibitory valance in the disease brain.

Survival of Cells Depends on Unknown Signals

GABAergic interneurons are essential for brain function because they balance the action of "excitatory" neurons in the cerebral cortex by producing inhibitory signals. Diseases like epilepsy, Alzheimer's, Huntington's, Parkinson's and schizophrenia are all variously linked to disruptions in this excitatory/inhibitory balance, and problems with the GABAergic interneurons have been documented in all these diseases.

These GABAergic interneurons are not born in the cerebral cortex — the part of the brain where they will ultimately become incorporated into functional circuits. Instead, they are created in a distant part of the developing brain and then migrate to their final destination. For decades, scientists have not known how the appropriate number of these interneurons is determined, how many are formed, when they die and how many survive after reaching the cerebral cortex. The recent publication addresses some of these unknowns, but also revealed an unexpected observation.

It is generally believed that neuronal numbers are determined by availability of survival signals provided by other target cells. This idea, generally known as the "neurotrophic hypothesis," is based on Nobel Prize-winning experiments in the 1940s showing how the survival of developing neurons in the spinal cord and peripheral nervous system is determined. That work showed that only the nerve fibers that could correctly connect to targets outside the nervous system would survive and that these targets produced a protein called nerve growth factor responsible for keeping the nerves alive.

For many years, the neurotrophic hypothesis has dominated ideas of how and why cells in the brain live and die. "The neurotrophic hypothesis has since been assumed to apply to all types neurons and all areas of the nervous system," said Southwell.

The assumption was that once the GABAergic interneurons winded their way to the right part of the brain, only those that melded with the other neurons already there would be protected by a protein or some other factor to stay alive. Instead, the survival of the transplanted interneurons was determined in a manner that was independent from competition for survival signals produced by other types of cells in the recipients.

While the new experiments do not overthrow this theory as it applies to how nerves outside the brain connect to their targets, they suggest there may be something else going on with GABAergic interneurons.

This work was funded by the California Institute for Regenerative Medicine, the John G. Bowes Research Fund, the Spanish Ministry of Science and Innovation, and the National Institute of Neurologic Disorders and Stroke, one of the National Institutes of Health, through grant #R01 NS071785 and # R01 NS048528.

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Journal Reference:

1. Derek G. Southwell, Mercedes F. Paredes, Rui P. Galvao, Daniel L. Jones, Robert C. Froemke, Joy Y. Sebe, Clara Alfaro-Cervello, Yunshuo Tang, Jose M. Garcia-Verdugo, John L. Rubenstein, Scott C. Baraban, Arturo Alvarez-Buylla. Intrinsically determined cell death of developing cortical interneurons. Nature, 2012; DOI: 10.1038/nature11523

Researchers at Western University have created a mouse model that reproduces some of the chemical changes in the brain that occur with Alzheimer's, shedding new light on this devastating disease. Marco Prado, Vania Prado and their colleagues at the Schulich School of Medicine & Dentistry's Robarts Research Institute, looked at changes related to a neurotransmitter or chemical messenger, named acetylcholine (ACh), and the kinds of memory problems associated with it.

The research is now published online by PNAS.

The researchers, including first author Amanda Martyn, created a mouse line that doesn't have enough ACh being secreted by neurons in the same brain regions affected by Alzheimer's disease. They found this neurochemical failure caused problems with spatial memory, the stored information that is needed for navigating one's environment. For instance, the memory needed to drive across town. They also found the reduction of ACh led to hyperactivity, which many patients with Alzheimer's experience.

"Once we reproduced that neurochemical failure, we asked, 'how does that affect spatial memory, how does it affect learning?' We found mice that don't have that particular chemical messenger in specific areas of the brain, have problems with spatial memory, for example," says Marco Prado. "This reveals specific types of cognitive deficits that we can hope to improve with drugs that boost this chemical messenger."

Scientists from the University of Leeds have found that the protein called prion helps our brains to absorb zinc, which is believed to be crucial to our ability to learn and the wellbeing of our memory.

The findings published Oct. 16 in Nature Communications show that prion protein regulates the amount of zinc in the brain by helping cells absorb it through channels in the cell surface. It is already known that high levels of zinc between brain cells are linked with diseases such as Alzheimer's and Parkinson's.

Professor Nigel Hooper from the University's Faculty of Biological Sciences explains: "With aging, the level of prion protein in our brains falls and less zinc is absorbed by brain cells, which could explain why our memory and learning capabilities change as we get older. By studying both their roles in the body, we hope to uncover exactly how prion and zinc affect memory and learning. This could help us better understand how to maintain healthy brain cells and limit the effects of aging on the brain."

Whilst the abnormal infectious form of prion — which causes Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE) in cattle — has been extensively studied, the Leeds team is among the first to investigate the role of the 'normal' form of the protein.

Lead researcher, Dr Nicole Watts, says: "Zinc is thought to aid signalling in the brain as it's released into the space between brain cells. However, when there's too much zinc between the brain cells it can become toxic. High levels of zinc in this area between the brain cells are known to be a factor in neurodegenerative diseases, so regulating the amount of absorption by the cells is crucial."

The research, funded by the Medical Research Council, Wellcome Trust and Alzheimer's Research UK, may have implications for how we treat — and possibly prevent — neurodegenerative diseases in the future.

Dr Simon Ridley, Head of Research at Alzheimer's Research UK, said: "We're pleased to have helped support this study, which has uncovered new information that could one day aid the development of new treatments for Alzheimer's. One next step would be to understand how regulating zinc levels may affect the progress of the disease. Results like these have the potential to lead to new and effective treatments — but for that to happen, we must build on these results and continue investing in research."

A new study shows that having a high amount of beta amyloid or "plaques" in the brain associated with Alzheimer's disease may cause steeper memory decline in mentally healthy older people than does having the APOE Ε4 allele, also associated with the disease.

The study is published in the October 16, 2012, print issue of Neurology®, the medical journal of the American Academy of Neurology.

"Our results show that plaques may be a more important factor in determining which people are at greater risk for cognitive impairment or other memory diseases such as Alzheimer's disease," said study author Yen Ying Lim, MPsych, with the University of Melbourne in Victoria, Australia. "Unfortunately, testing for the APOE genotype is easier and much less costly than conducting amyloid imaging."

For the study, 141 people with an average age of 76 who were free of any problems in memory and thinking underwent PET brain scans and were tested for the APOE gene. Their memory and thinking was then tracked over the following year and a half, using a set of computer-based cognitive assessments that were based on playing card games and remembering word lists.

The study found that after a year and a half, people who had more brain plaques at the start of the study had up to 20 percent greater decline on the computer based assessments of memory than did those who had fewer brain plaques. The study also found that while carriers of the APOE Ε4 allele also showed greater decline on the memory assessments than those who did not have the allele, carrying the Ε4 allele did not change the decline in memory related to the plaques.

"Our finding that brain plaque-related memory decline can occur while people still have normal memory and thinking shows that these plaque-related brain changes can be detected and measured while older people are still healthy. This provides an enormous opportunity for understanding the development of early Alzheimer's disease and even a sound basis for the assessment of plaque-targeting therapies," said Lim.

The study was supported by the Australian Commonwealth Scientific Industrial and Research Organization, Edith Cowan University, Mental Health Research Institute, Alzheimer's Australia, National Aging Research Institute, Austin Health, CogState Ltd., Hollywood Private Hospital, Sir Charles Gardner Hospital, the Australian National Health and Medical Research Council, the Dementia Collaborative Research Centers Program and the Science and Industry Endowment Fund.

Curtailing the imminent rise in Alzheimer's disease (AD) will require early, accurate diagnostic tests and treatments, and researchers are closer to achieving these two goals.

New findings in medical imaging, molecular analysis of neurological diseases, and development of treatments using mouse models were presented at Neuroscience 2012, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.

AD is the most common cause of dementia and currently affects 5 million people in the United States. By 2015, this number could increase to 13 million people.

Today's new findings show that:

• Changes in brain function occur many years before symptoms in people with AD; these changes could be detected by PET scans and might one day be used to identify people at risk for developing the disease (Lori Beason-Held, PhD, abstract 545.22).
• A new drug that targets biochemical changes in proteins improved symptoms and increased survival in a mouse model of AD, but just how it works is a mystery (Fred Van Leuven, PhD, abstract 416.08).
• An antibody-based probe that uses nanotechnology and magnetic resonance imaging can distinguish between diseased and non-diseased brain tissue and could lead to a test for early detection of AD (William Klein, PhD, abstract 753.21).
• AD, Parkinson's disease, and Dementia with Lewy Bodies have specific molecular signatures caused by epigenetics — mechanisms that determine how and when DNA is expressed — that could assist in accurate diagnosis and earlier treatment (Paula Desplats, PhD, abstract 50.17).
• A new mouse model for AD gives researchers more control over an Alzheimer's-related protein in mice, and could lead to better research on effective treatments (Alena Savonenko, MD, PhD, abstract 416.04).

"Being able to detect AD early — perhaps even before symptoms begin — is an essential pre-condition if we are to develop effective treatments that slow or stop the changes that occur in the brain during Alzheimer's. Our studies in mice already tell us this," said press conference moderator Sam Gandy, PhD, MD, of the Mount Sinai School of Medicine in New York City, an expert on AD and dementia. "Being able to distinguish AD from other neurodegenerative diseases will help us give the right treatments to the right patients."

Rapamycin, a drug used to prevent rejection in transplants, could delay the onset of neurodegenerative diseases such as Alzheimer's and Parkinson's.

This is the main conclusion of a study published in the Nature in which has collaborated the researcher Isidro Ferrer, head of the group of Neuropathology at the Bellvitge Biomedical Research Institute (IDIBELL) and the Bellvitge University Hospital and Full Professor of Pathological Anatomy at the University of Barcelona. The research was led by researchers from the International School for Advanced Studies (SISSA) in Trieste (Italy).

The collaboration of the research group led by Dr. Ferrer with SISSA researchers began five years ago when they observed that Parkinson's patients showed a deficit in UCHL1 protein. At that time, researchers didn't know what mechanism produced this deficit. To discover it a European project was launched. It was coordinated by the Italian researchers and participated by other European research groups, including the group led by Dr. Ferrer. The project, called Dopaminet, focused on how dopaminergic neurons (brain cells whose neurotransmitter is dopamine) are involved in Parkinson's disease.

Contrary to most common hypothesis that a DNA fragment encodes a protein through a messenger RNA molecule, the researchers found that it also works in reverse. They found a balance between the protein and its mirror protein, which is configured in reverse, and they are mutually controlled. If the protein mirror is located in the nucleus of the cell, it does not interact with the protein, while if it is in the cytoplasm, then both of them interact.

In the case of Parkinson's disease the protein UCHL1 appears reduced and also its mirror protein is localized in the nucleus, and in the cytoplasm. Thus, the researchers sought a method to extract the mirror protein from the nucleus and made it interact with the original UCHL1 protein. The authors found that rapamycin was able to extract them from the nucleus. The drug allows the two proteins, the UCHL1 and its mirror, hold together in the cytoplasm, which would correct the mistakes that occur in Parkinson's disease.

This in vitro research has allowed describing a new unknown mechanism. It is necessary that the UCHL1 mirror protein should accumulate in the nucleus and escape from the cytoplasm and join the UCLH1 protein. The combination of both makes the system work.

"The rapamycin can not cure Parkinson's disease, but it may delay the onset of neurodegenerative diseases such as Alzheimer's and Parkinson's itself. Rapamycin can protect and delay the beginning of these diseases. It can complete the treatment, but it should be combined with other existing treatments," explains Isidro Ferrer.

Anyway, it is still far from application in patients. The next step is to validate these results in animal models and study the effects of rapamycin in combination with other drugs.

New findings presented today report the important role sleep plays, and the brain mechanisms at work as sleep shapes memory, learning, and behavior. The findings were presented at Neuroscience 2012, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.

One in five American adults show signs of chronic sleep deprivation, making the condition a widespread public health problem. Sleeplessness is related to health issues such as obesity, cardiovascular problems, and memory problems.

Today's findings show that:

• Sleepiness disrupts the coordinated activity of an important network of brain regions; the impaired function of this network is also implicated in Alzheimer's disease (Andrew Ward, abstract 909.05).
• Sleeplessness plays havoc with communication between the hippocampus, which is vital for memory, and the brain's "default mode network;" the changes may weaken event recollection (Hengyi Rao, PhD, abstract 626.08).
• In a mouse model, fearful memories can be intentionally weakened during sleep, indicating new possibilities for treatment of post-traumatic stress disorder (Asya Rolls, abstract 807.06).
• Loss of less than half a night's sleep can impair memory and alter the normal behavior of brain cells (Ted Abel, PhD, abstract 807.13).

Other recent findings discussed show:

• How sleep enables the remodeling of memories — including the weakening of irrelevant memories — and the coherent integration of old and new information (Gina Poe, PhD).
• The common logic behind seemingly contradictory theories of how sleep remodels synapses, aiding cognition and memory consolidation (Giulio Tononi, MD, PhD).

"As these research findings show, we cannot underestimate the importance of a good night's sleep," said press conference moderator Clifford Saper, PhD, MD, from the Harvard Medical School, an expert on sleep and its deprivation. "Brain imaging and behavioral studies are illuminating the brain pathways that are blocked or contorted by sleep deprivation, and the risks this poses to learning, memory, and mental health."

This research was supported by national funding agencies such as the National Institutes of Health, as well as private and philanthropic organizations.

A new study from Georgia Tech and the University of Toronto suggests that memory impairments for people diagnosed with early stage Alzheimer's disease may be due, in part, to problems in determining the differences between similar objects. The findings also support growing research indicating that a part of the brain once believed to support memory exclusively — the medial temporal lobe — also plays a role in object perception.

The results are published in the October edition of Hippocampus.

Mild cognitive impairment (MCI) is a disorder commonly thought to be a precursor to Alzheimer's disease. The study's investigators, partnering with the Emory Alzheimer's Disease Research Center, tested MCI patients on their ability to determine whether two rotated, side-by-side pictures were different or identical.

In the high-interference trials, many photos of the same thing (a blob-like object) were shown. The photos varied only slightly when they weren't a perfect match, either by shape, color or fill pattern. As expected, MCI patients struggled greatly to identify identical pairings.

In the low-interference trials, these blob-like objects were interspersed with trials in which non-matches were more extreme and varied widely. For example, a picture of a butterfly was shown next to a photo of a microwave. Interspersing the very similar blob-like objects with photos of dissimilar objects greatly reduced the amount of interference.

"Minimizing the degree of perceptual interference improved patients' object perception by reducing the number of visually similar features," said project leader Rachel Newsome, a University of Toronto Ph.D. student and Georgia Tech graduate.

The findings suggest that, under certain circumstances, reducing "visual clutter" could help MCI patients with everyday tasks. For example, buttons on a telephone tend to be the same size and color. Only the numbers are different — a very slight visual difference for someone who struggles with object perception. One solution could be a phone with varying sized buttons and different colors.

People diagnosed with MCI weren't the only ones to struggle in the study. The researchers performed the same tests on candidates at-risk for MCI, people who had previously shown no signs of cognitive impairment. They performed the same as those with MCI, suggesting that the perception test could be used as an early indicator of cognitive impairment.

"People often associate MCI and dementia solely with memory impairment," said Georgia Tech Psychology Assistant Professor Audrey Duarte, one of the study's authors. "Memory and perception appear to be intertwined in the same area of the human brain."

Duarte and her colleagues are among the growing number of researchers studying Alzheimer's who believe damage to a small area of the medial temporal lobes, the perirhinal cortex, affects object perception.

"Not only does memory seem to be very closely linked to perception, but it's also likely that one affects the other," said Toronto's Morgan Barense, the final member of the team. "Alzheimer's patients may have trouble recognizing a loved one's face, not only because they can't remember it, but also because they aren't able to correctly perceive its distinct combination of features to begin with."

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Journal Reference:

1. Rachel N. Newsome, Audrey Duarte, Morgan D. Barense. Reducing perceptual interference improves visual discrimination in mild cognitive impairment: Implications for a model of perirhinal cortex function. Hippocampus, 2012; 22 (10): 1990 DOI: 10.1002/hipo.22071

Although they're a common nuisance in the home, fruit flies have made great contributions to research in genetics and developmental biology. Now a Tel Aviv University researcher is again turning to this everyday pest to answer crucial questions about how neurons function at a cellular level — which may uncover the secrets of neurological disorders such as Alzheimer's disease.

Approximately 75 percent of the genes that are related to diseases in humans are also to be found in the fly, says Ya'ara Saad, a PhD candidate in the lab of Prof. Amir Ayali at TAU's Department of Zoology and the Sagol School of Neurosciences. There are many similarities in the functioning of the nervous system in both organisms, and by observing how neuronal networks taken from the fly grow and function outside of the body, there are many clues to the way human neuronal cells interact and the factors that influence their viability and physiology.

Saad's work, which has been published in the Journal of Molecular Histology, could help researchers to better understand how individual neurons are physically and chemically altered in response to disease and therapeutic intervention, and lead to new treatments.

Testing medications cell by cell

Saad is exploring how neural networks develop one neuron at a time. In the lab, the researchers break the fly's nervous system down into single cells, separate these cells, then place them at a distance from each other in a Petri dish. After a few days, the neurons begin to grow towards one another and establish connections, and then migrate to form clusters of cells. Finally, they re-organize themselves to form a sophisticated network, says Saad. Because these experiments uniquely allow researchers to concentrate on individual neurons, they can perform specific measurements of proteins, note electrical activity, watch synapses develop, and see how physical changes take shape.

Saad and her fellow researchers are using this technique to observe how neurodegenerative diseases take over the neurons and to potentially test various medicinal interventions. In their experiments, one group of flies is genetically modified so that it expresses a peptide called Amyloid Beta, found in protein-based plaques of human Alzheimer's disease patients. The results of these studies are then compared to those of a non-modified control group. Both strains of flies are provided by Prof. Daniel Segal of TAU's Department of Molecular Microbiology and Biotechnology.

Previous studies performed on flies expressing Amyloid Beta showed that they demonstrate Alzheimer's-like symptoms such as motor problems, impaired learning capabilities, and shorter lifespans. While this peptide has been researched for quite some time, scientists still do not know how it functions. Saad says her work may help unlock the mystery of this function. "Now I can really get into the molecular operation of Amyloid Beta inside the cell. I can watch the dysfunction in the synapses, monitor the proteins involved, and record electrical activity in a much more accessible way," she says.

Testing pharmacological agents is as simple as putting the medication into the dish and following how the cells change in response, Saad explains. Her next step will be to test various medications and search for a treatment that restores normal function, morphology, and chemical make-up to the neurons.

The benefits of invertebrates

As one of the first organisms for which scientists cracked the entire genome, there is a wealth of genetic information about the fruit fly, making it an ideal subject for her research, explains Saad. Though fly brains are simpler than those of human brains, the neurons are the same size and structure, and possess similar chemical activity. With a life span of 30 days on average, flies have a short aging process, an important consideration for the study of neurodegenerative diseases.

"A lot of basic discoveries in neurobiology have been made on invertebrates. If you want to see things on a cellular level, there are a lot of advantages to using these models," says Saad. She also says that using insects instead of mammals as experimental subjects has an additional plus: no ethical approval is necessary until the research is advanced enough to move on to more sophisticated life forms.

The combination of two neuroprotective therapies, voluntary physical exercise, and the daily intake of melatonin has been shown to have a synergistic effect against brain deterioration in rodents with three different mutations of Alzheimer's disease.

A study carried out by a group of researchers from the Barcelona Biomedical Research Institute (IIBB), in collaboration with the University of Granada and the Autonomous University of Barcelona, shows the combined effect of neuroprotective therapies against Alzheimer's in mice.

Daily voluntary exercise and daily intake of melatonin, both of which are known for the effects they have in regulating circadian rhythm, show a synergistic effect against brain deterioration in the 3xTg-AD mouse, which has three mutations of Alzheimer's disease.

"For years we have known that the combination of different anti-aging therapies such as physical exercise, a Mediterranean diet, and not smoking adds years to one's life," Coral Sanfeliu, from the IIBB, explained. "Now it seems that melatonin, the sleep hormone, also has important anti-aging effects."

The experts analysed the combined effect of sport and melatonin in 3xTg-AD mice which were experiencing an initial phase of Alzheimer's and presented learning difficulties and changes in behaviour such as anxiety and apathy.

The mice were divided into one control group and three other groups which would undergo different treatments: exercise -unrestricted use of a running wheel-, melatonin -a dose equivalent to 10 mg per kg of body weight-, and a combination of melatonin and voluntary physical exercise. In addition, a reference group of mice were included which presented no mutations of the disease.

"After six months, the state of the mice undergoing treatment was closer to that of the mice with no mutations than to their own initial pathological state. From this we can say that the disease has significantly regressed," Sanfeliu states.

The results, which were published in the journal Neurobiology of Aging, show a general improvement in behaviour, learning, and memory with the three treatments.

These procedures also protected the brain tissue from oxidative stress and provided good levels of protection from excesses of amyloid beta peptide and hyperphosphorylated TAU protein caused by the mutations. In the case of the mitochondria, the combined effect resulted in an increase in the analysed indicators of improved performance which were not observed independently.

Treatment not easily transferable to humans

"Transferring treatments which are effective in animals to human patients is not always consistent, given that in humans the disease develops over several years, so that when memory loss begins to surface, the brain is already very deteriorated," the IIBB expert points out.

However, several clinical studies have found signs of physical and mental benefits in sufferers of Alzheimer's resulting from both treatments. The authors maintain that, until an effective pharmacological treatment is found, adopting healthy living habits is essential for reducing the risk of the disease appearing, as well as reducing the severity of its effects.

The melatonin debate

The use of melatonin, a hormone synthesized from the neurotransmitter serotonin, has positive effects which can be used for treating humans. With the approval of melatonin as a medication in the European Union in 2007, clinical testing on this molecule has been increasing. It has advocates as well as detractors, and the scientific evidence has not yet been able to unite the differing views.

According to the Natural Medicines Comprehensive Database, melatonin is probably effective in sleeping disorders in children with autism and mental retardation and in blind people; and possibly effective in case of jet-lag, sunburns and preoperative anxiety.

"However, other studies which use melatonin as medication show its high level of effectiveness," Darío Acuña-Castroviejo explained. He has been studying melatonin for several years at the Health Sciences Technology Park of the University of Granada.

The expert points out that international consensus already exists, promoted by the British Association for Psychopharmacology -also published in the Journal of Psychopharmacology in 2010-, which has melatonin as the first choice treatment for insomnia in patients above the age of 55. This consensus is now being transferred to cases of insomnia in children.

Its use in treating neurodegenerative diseases is acquiring increasing scientific support in lateral amyotrophic sclerosis, in Alzheimer's, and Duchenne muscular dystrophy.

"Even though many more studies and clinical tests are still required to assess the doses of melatonin which will be effective for a wide range of diseases, the antioxidant and anti-inflammatory properties of melatonin mean that its use is highly recommended for diseases which feature oxidative stress and inflammation," Acuña-Castroviejo states.

This is the case for diseases such as epilepsy, chronic fatigue, fibromyalgia, and even the aging process itself, where data is available pointing to the benefits of melatonin, though said data is not definitive.