Psychosurgery is making a comeback. Recently published case series have shown encouraging results of so-called deep brain stimulation (DBS) in treatment-resistant obsessive-compulsive disorder, depressive disorders, and Tourette syndrome. In the current issue of Deutsches Ärzteblatt International, authors Jens Kuhn (University of Cologne) and Theo P J Gründer (Max Planck Institute, Cologne) and their co-authors provide an introduction to the method (Dtsch Arztebl Int 2010; 107(7)105-13).

In order to determine the clinical utility of DBS in psychiatric disorders, the authors evaluated therapeutic studies from 1980 to 2009. They found improvement rates of between 35% and 70% in treatment-resistant obsessive-compulsive disorder, depression, and Tourette syndrome. The rate of side effects associated with DBS was usually low and mostly reversible by modulating the stimulation parameters.

This favourable side effect profile is not all that surprising because DBS is a procedure that is well known; it has been in use for 20 years. In Parkinson’s disease and essential tremor, the method has proved to be so effective that it has been licensed as a therapeutic option for many years. To administer DBS, two electrodes are implanted into the patient that deliver continuous, high frequency, short electrical impulses, enabling modulation of the functional neuronal circuits. The electrodes are connected via a cable to an impulse generator, which is usually implanted below the collarbone.

Although DBS seems to offer new perspectives for the treatment of psychiatric disorders, further studies into its efficacy, mechanisms of action, and side effect profile and especially its long term course are needed.

Scientists are beginning to find out why people with Parkinson’s disease often feel socially awkward. Parkinson’s patients find it harder to recognize expressions of emotion in other people’s faces and voices, report two studies published by the American Psychological Association.

One of the studies raises questions about how deep brain stimulation, the best available treatment for patients who no longer respond to medication, more strongly affects the recognition of fear and sadness.

A neurodegenerative disorder, Parkinson’s causes tremors, stiffness and balance problems, as well as fairly frequent depression and dementia.

In the March issue of Neuropsychology, Heather Gray, PhD, and Linda Tickle-Degnen, PhD, report that people with Parkinson’s disease, compared with matched controls, often have difficulty discerning how others are feeling.

Their meta-analysis of 34 different studies using data from 1,295 participants shows a robust link between Parkinson’s and specific deficits in recognizing emotions, especially negative emotions, across different types of stimuli and tasks.

The meta-analysis, conducted at Harvard Medical School and Tufts University, found that patients typically had some degree of problem identifying emotion from faces and voices.

Further clarification is provided in a second study that showed that deep-brain stimulation, compared with medication, caused a consistently large deficit in the recognition of fear and sadness two key facial expressions that, when understood, aid survival. That study is published in the January issue of Neuropsychology.

Researchers led by Julie Péron, PhD, at the Centre Hospitalier Universitaire de Rennes in France, compared the ability of people with Parkinson’s in three different groups to recognize facial emotions: 24 advanced patients implanted with deep-brain stimulators after they didn’t respond or were sensitive to oral levodopa (the usual drug for the disease); 20 advanced patients given apomorphine hydrochloride by injection or infusion pump while they waited an implant; and 30 healthy controls.

Researchers tested all participants using standard photographs of facial expression before and three months after they were treated. Before implantation of the stimulators, all participants read facial expressions equally well.

Patients in the surgical group were implanted with stimulators, electrical devices that prod the brain’s subthalamic nucleus, a small, lens-shaped structure, to normalize the nerve signals that control movement. This nucleus is part of the basal ganglia system, which is thought to integrate movement, cognition and emotion.

Three months after treatment, only the patients with stimulators not the drug-treated patients or the healthy controls were significantly worse at recognizing fear and sadness. Patients with stimulators confused those expressions with others, such as surprise, or even no emotion. Medicated patients and healthy controls were either accurate about fear and sadness or occasionally mistook them for other negative emotions, such as disgust.

“Having Parkinson’s predisposes an individual to errors in emotion recognition,” said Gray. “The research in France, along with previous studies, indicates that deep-brain stimulation produces an even more severe deficit.”

Why would treating a movement disorder affect the perception of emotions? Implants affect a part of the brain that reaches across functions, so the authors suggested that the same electrical stimulation that calms over-excited motor activity may also somehow inhibit emotional processing.

Although the impact of Parkinson’s and deep-brain stimulation varies by patient, it’s important to understand. “The first step is to educate patients and their close associates about the potential for emotion recognition difficulties, so they can learn to manage some of the social consequences, such as misunderstanding and frustration,” said Gray and Tickle-Degnen. The next step might be training in emotion recognition, which they said has shown promise.

Treadmill training can be used to help people with Parkinson’s disease achieve better walking movements, say researchers. In a systematic review of the evidence, Cochrane Researchers concluded treadmill training could be used to improve specific gait parameters in Parkinson’s patients.

Gait hypokinesia, characterised by slowness of movement, is one of the main movement disorders that affects Parkinson’s patients and can have a major impact on quality of life. More recently, health professionals have started incorporating exercise into treatment regimes as a useful complement to traditional drug therapies. Training on treadmills is one option that may help to improve movement.

The researchers analysed data from eight trials including 203 patients for the review, published in The Cochrane Library. They compared treadmill training versus no treadmill training, using effects on walking speed, stride length, number of steps per minute (cadence) and walking distance to measure improvement in gait. Treadmill training had a positive impact on each of these measurements, apart from cadence.

“Treadmill training appears to be a safe and effective way of improving gait in patients with Parkinson’s disease,” said lead researcher Jan Mehrholz, of the Wissenschaftliches Institut in Kreischa, Germany. “Crucially, we saw very few adverse effects or drop outs in patients given this type of rehabilitation therapy.”

However, the researchers say the findings must be treated with care as they are based on a limited number of small trials. “There is still a need for larger trials to establish if treadmill training can be safely used as a routine therapy for Parkinson’s patients,” said Merhholz. “We also need to answer basic questions about how long the benefits last and what a good training programme should consist of. For instance, how often and how long should patients train for?”

Cognitive fluctuations, or episodes when train of thought temporarily is lost, are more likely to occur in older persons who are developing Alzheimer’s disease than in their healthy peers, according to scientists at Washington University School of Medicine in St. Louis.

Cognitive fluctuations include excessive daytime sleepiness, staring into space and disorganized or illogical thinking.

“If you have these lapses, they don’t by themselves mean that you have Alzheimer’s,” says senior author James Galvin, M.D., a Washington University neurologist at Barnes-Jewish Hospital. “Such lapses do occur in healthy older adults. But our results suggest that they are something your doctor needs to consider if he or she is evaluating you for problems with thinking and memory.”

The study appears in the Jan. 19 issue of Neurology.

Earlier research had associated cognitive fluctuations with another form of dementia called dementia with Lewy bodies, but little information existed on the potential for links between Alzheimer’s and such lapses.

Data for the new study came from Alzheimer’s disease evaluations of 511 older adults with memory problems. Average age of the participants was 78. Researchers gave participants standard tests of thinking and memory skills. They also interviewed participants and a family member, checking for prolonged daytime sleepiness, drowsiness or lethargy in spite of sufficient sleep the night before, periods of disorganized or illogical thinking, or instances of staring into space for long periods of time.

A total of 12 percent of the participants had at least three of these symptoms, meeting the criteria for cognitive fluctuations. Those with mental lapses were 4.6 times more likely to be diagnosed with Alzheimer’s. Of 216 diagnosed with very mild or mild dementia, 25 had mental lapses; of the 295 with no dementia, only two had mental lapses. In addition, participants with mental lapses did worse on tests of memory and thinking than people without mental lapses.

“We have some ideas about why the biology of dementia with Lewy bodies causes these mental lapses, but nothing comparable for Alzheimer’s,” Galvin says. “It’s possible that some of the patients who were diagnosed with Alzheimer’s disease in this study will go on to develop dementia with Lewy bodies, but at the time of the study, they weren’t showing any of the Lewy body dementia’s core features.”

Lewy body dementia, which causes clumps of proteins known as Lewy bodies to form in neurons, is thought to be the second most common form of dementia after Alzheimer’s. Clinically, it can overlap with Parkinson’s disease and Alzheimer’s disease. Pronounced cognitive fluctuations are a hallmark of Lewy body dementia, as are visual hallucinations and rapid eye movement behavior sleep disorder.

We all have at one time or another experienced the typical signs of an infection: the fever, the listlessness, the lack of appetite. They are orchestrated by the brain in response to circulating cytokines, the signaling molecules of the immune system. But just how cytokines’ reach extends beyond the almost impenetrable blood-brain barrier has been the topic of much dispute.

In their latest study, researchers at the Salk Institute for Biological Studies describe how, depending on the nature of the stimulus, resident macrophages lined up along the blood-brain barrier play opposing roles in the transmission of immune signals into the brain.

“These macrophages act as accelerators to enlist the brain’s participation in dealing with immune insults, but when necessary slam on the brakes to prevent the central inflammatory response from going overboard,” explains postdoctoral researcher Jordi Serrats, Ph.D., who co-led the study with Jennifer C. Schiltz, Ph.D., formerly a postdoctoral researcher in the Salk’s Neuronal Structure and Function Laboratory and now an assistant professor at the Uniformed Services University in Bethesda, Maryland.

The Salk researchers’ findings, which are published in the Jan. 14, 2010 edition of the journal Neuron, may pave the way for novel therapies for sufferers of chronic neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS), Parkinson’s, Alzheimer’s and prion diseases, in which central inflammatory mechanisms play an important role.

“The fact that we have identified a potent anti-inflammatory mechanism in the brain presents a new target to intervene in the wide range of central nervous system diseases that possess an inflammatory component,” says the study’s senior author, Paul E. Sawchenko, Ph.D., a professor in the Neuronal Structure and Function Laboratory.

In response to an infection, inflammatory cytokines such as interleukin-1 are generated at the site of infection. These cytokines circulate in the blood and communicate with neurons in the brain to engage the hypothalamo-pituitary-adrenal (HPA) axis, an integral part of the brain’s stress response machinery. The HPA axis involves the interaction of the hypothalamus, the pituitary gland, which sits just below the hypothalamus and the adrenal glands at the top of the kidneys.

Like a central command center, the hypothalamus sends out corticotropin-releasing factor, which stimulates the pituitary gland to secrete adrenocorticotropic hormone. The latter signals the adrenal glands to ramp up the production of glucocorticoids, which mobilize energy reserves to cope with inflammatory insults. But they also act as very powerful immunosuppressants preventing excessive cytokine production and immune cell proliferation.

“Cytokines are big molecules that don’t cross the blood-brain barrier freely,” says Sawchenko. “The question of how these molecules access the brain to trigger this whole array of adaptive responses such as fever, inactivity, sleepiness, and activation of the brain’s stress response machinery has been a nagging problem in the side of neuroimmunology for many years.”

Earlier research by Sawchenko and others suggested a vascular route whereby cytokines interact with vessel walls to generate secondary messengers, which then engage the relevant circuitry in the brain. Tightly packed endothelial cells, which line almost 400 miles of narrow capillaries throughout the brain, are perfectly positioned to record circulating immune signals but they require a very strong signal to become activated. Perivascular macrophages, on the other hand, are more sensitive but don’t have direct access to the bloodstream.

To disentangle the exact role of these two cell types, Serrats took advantage of the macrophages’ ability to engulf and ingest solid particles. He injected liposomes containing clodronate, a drug that can cause cell death, into the lateral cerebral ventricle. The liposomes were taken up by the macrophages, which were selectively killed off.

Without perivascular macrophages, the animals were unable to respond to blood-borne interleukin-1 and initiate the brain’s so-called acute phase responses, which help the body deal with the challenge at hand but also cause the familiar feeling of “being sick.” But to their surprise, the Salk researchers found that the same cells put a damper on the pro-inflammatory activities of endothelial cells, which form the lining of blood vessels and are only stirred to action-but very powerfully once they are-when they encounter lipopolysaccharide, a key component of the cell wall of certain bacteria.

“Many neurodegenerative diseases are worsened by systemic inflammation or infections,” says Sawchenko. “Once we identify the molecules that mediate the two-way communication between perivascular macrophages and endothelial cells we can develop strategies for managing the adverse health consequences of central inflammatory responses.”

An article Online First and in the February edition of The Lancet Neurology reports that brain scans using positron emission tomography (PET) can identify with high accuracy which form of Parkinsonism a patient has. Such early diagnosis is essential to make sure that patients receive the correct treatment and do not receive ineffective treatments due to misdiagnosis. The article is the work of Dr David Eidelberg, Center for Neurosciences,The Feinstein Institute for Medical Research, Manhasset, NY, USA, and colleagues.

Parkinson’s disease arising spontaneously can present with symptoms comparable to those of multiple system atrophy or progressive supranuclear palsy. The investigators aimed to assess in this study whether metabolic brain imaging combined with pattern analysis could accurately discriminate patients with different forms of Parkinsonism.

A total of 167 patients were assessed in this study. They were recruited from the New York area between 1998 and 2006. They all had parkinsonian features but uncertain clinical diagnosis. At the Feinstein Institute for Medical Research, all of the patients underwent a PET scan. The team of researchers developed an automated image-based classification procedure to tell apart individual patients with idiopathic Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. The likelihood of having each of the three diseases was calculated for each patient. A classification was made according to probability measurements. After imaging, movement disorders specialists who were unaware of the PET results assessed the patients for an average of 2.6 years before a final clinical diagnosis was made. Then, the accuracy of the initial image-based classification was evaluated and compared with the final clinical diagnosis.

Results indicated that image-based classification for idiopathic Parkinson’s disease had 84 percent sensitivity. Sensitivity measures the proportion of actual positives which are correctly identified as such. For instance, it is the percentage of sick people who are identified as having the condition. They had 97 percent specificity which measures the proportion of negatives that are correctly identified. 98 percent had positive predictive value (PPV) which is the proportion of patients with positive test results who are correctly diagnosed. 82 percent had negative predictive value (NPV) which is the proportion of patients with negative test results who are correctly diagnosed. Imaging classifications were also accurate for multiple system atrophy (85 percent sensitivity, 96 percent specificity, 97 percent PPV, and 83 percent NPV) and progressive supranuclear palsy (88 percent sensitivity, 94 percent specificity, 91 percent PPV, and 92 percent NPV). Dr Eidelberg comments: “The excellent specificity and PPV of the imaging classification makes this test suitable for diagnostic use rather than as a screening tool.”

In addition to those findings, the authors indicate that early and correct diagnosis is crucial to make sure that patients with the proper diagnosis are enrolled in drug trials for potentially disease-modifying drugs for the various parkinsonian disorders. Also, the authors wish to expand their work to be able to differentiate other forms of parkinsonism.

They comment: “Automated image-based classification has high specificity in distinguishing between parkinsonian disorders and could help in selecting treatment for early stage patients and identifying participants for clinical trials.”

They note: “Blinded, prospective imaging studies – ideally involving multiple centres, a larger validation group, repeat imaging, and more extensive post-mortem confirmation – are needed to establish the accuracy of this pattern-based categorisation procedure.”

In an associated comment, Professor Angelo Antonini, IRCCS San Camillo, Venice and Parkinson Institute, Milan, Italy, remarks: “The clinical and research relevance of these findings should not be underestimated. Neuroprotective and disease-modifying drug research is intensifying and results mostly rely on accurate early diagnosis.”

He writes in conclusion: “Although imaging might be cost effective for early diagnosis, I expect that these procedures will find their natural application in the identification of suitable candidates for drug trials or complex surgical procedures (eg, deep brain stimulation, stem-cell transplantation, or foetal tissue transplantation). However, additional blinded, prospective, multicentre studies will first be needed to confirm the accuracy of this pattern-based categorisation procedure.”

Several structurally similar small molecules appear capable of protecting cells from alpha-synuclein toxicity in multiple models of Parkinson’s disease, according to Whitehead Institute researchers. Misfolded copies of the alpha-synuclein protein in brain cells are a hallmark of Parkinson’s disease.

“In this research, we used yeast as a Parkinson’s disease model system to identify the compounds that really work in two higher order model systems of Parkinson’s,” says Julie Su, a first co-author on the paper describing the research and a former postdoctoral researcher in Whitehead Member Susan Lindquist’s lab. “And that shows that those compounds’ targets are highly conserved over a billion years of evolution.”

Parkinson’s disease is a neurodegenerative disorder characterized by tremors, muscle rigidity, and slowed movements. In the neurons of Parkinson’s patients’ brains, researchers have noted Lewy bodies, abnormal spheres composed of the protein alpha-synuclein. There is currently no cure for the disease, and current Parkinson’s therapies only address disease symptoms, not the disease’s cellular cause.

In their article in Disease Models and Mechanisms (DMM), Lindquist scientists report that four related small molecules prevented the development of several cellular traits associated with Parkinson’s disease, including the accumulation of alpha-synuclein deposits in the cell, improper protein trafficking from one organelle to another, and damage inflicted on the cells’ engines, the mitochondria.

The research is based on a type of brewer’s yeast modified to produce too much of the alpha-synuclein protein in its cells. The resulting cells manifest adverse effects similar to those experienced in brain cells from Parkinson’s patients.

Using this yeast strain, the Lindquist team screened 115,000 small compounds to see which ones alleviate the Parkinson’s-like traits. During a screen, a compound is added to a small amount of yeast. Researchers can then easily and efficiently detect if that compound changes the yeast’s growth rate, compared to a control. The technique takes advantage of the yeast’s normally fast growth, which allows researchers to quickly test thousands of compounds, a process that is not possible in other frequently-used Parkinson’s disease models.

Four compounds were found to restore the alpha-synuclein yeast cells’ growth to 50% of normal yeast cells. Yeast cells that were not treated with the compounds died. The four compounds have similar chemical structures, a finding that indicates they may be acting on the same target or targets. The researchers also identified two commercially available compounds with similar chemical structures and used those in further tests.

To determine if the six compounds would work in animal models of Parkinson’s, the scientists tested the compounds in the round worm Caenorhabditis elegans and in rat neurons. In both of these disease models, cells overproduce alpha-synuclein resulting in the same deleterious effects as in the yeast model. During testing, the first four compounds were able to rescue the round worms, while in the rat neurons, three of the four original compounds and one of the commercial compounds improved the nerve cells’ growth.

In all of the models, the compounds improved protein trafficking and decreased mitochondrial damage.

“Those two things are obviously related,” says Pavan Auluck, first co-author and a visiting scientist in the Lindquist lab. “We’re trying to figure out what the connections are between them. And there are a number of ways they can be related.”

Lindquist agrees: “There are very deeply rooted processes that connect protein trafficking and mitochondrial viability,” says Lindquist, who is also a Howard Hughes Medical Institute investigator and a professor of biology at MIT. “That emphasizes that the underlying problem caused by alpha-synuclein is a general cellular defect that is part of the machinery of all eukaryotic cells. The specific problems in Parkinson’s are due to the neurons being particularly sensitive to that process going awry.”

As for the future of the specific compounds identified in this study, Daniel Tardiff, a Lindquist postdoctoral researcher, remains optimistic.

“Theoretically if a compound is having a beneficial effect on yeast cells, and in a worm, and in primary neurons, then possibly through years and years of work, it might actually be a potential therapeutic avenue or drug,” says Tardiff. “Though we started in yeast, one of those compounds could actually have some potential for human health in Parkinson’s disease. That’s always a lofty goal.”

Excessive sway during quiet standing is a common and significant consequence of chronic alcoholism, even after prolonged sobriety, and can lead to fall-related injury and even death. A new study of residual postural instability in alcohol-abstinent men and women shows that alcoholics improve with prolonged sobriety, but the improvement may not fully erase the problem of instability.

Results will be published in the March 2010 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“Caricatures depict acutely intoxicated individuals with a stumbling, weaving, wobbly gait,” said Edith V. Sullivan, professor in the department of psychiatry and behavioral sciences at Stanford University School of Medicine and corresponding author for the study. “With sobriety, gait and balance become stable. However, even with prolonged sobriety, people with long-term chronic alcohol dependence can have difficulty in standing upright. Their balance can be marked by sway that exceeds what most of us experience while standing still in one place, especially with feet together and hands down by one’s side, that is, without use of natural stabilizing factors.”

Sullivan said that quantifying the sway can be accomplished by using a force plate to record the sway path in fractions of an inch over fractions of seconds during quiet standing. This provides “sway path tracking” as well as measurement of body tremor, which are micro-movements often reflective of central nervous system damage that can be found both in Parkinson’s disease and alcoholism.

Researchers used a “force platform” to measure postural sway – with and without stabilizing conditions from touch, vision and stance – in 34 alcoholic men, 15 alcoholic women, 22 control men, and 29 control women. They then analyzed “biomechanical control mechanisms” that indicate skeletomuscular control over balance, which – under normal circumstances – means the muscles, joints, and skeletal structure are working synergistically, in a give-and-take manner.

“Results show the sway paths of alcoholics are longer and cover a wider area than those of controls for a given time,” said Sullivan. “However, it is important to note that the standing stability of sober alcoholics can be improved by using stabilizing factors. These factors can include simple aids like turning a light on in a dark room, touching a banister while walking down a flight of stairs, or walking or standing with feet apart rather than with ankles close together.”

Sullivan added that the disproportionately greater sway in the anterior-posterior (front-to-back) direction than the medial-lateral (side-to-side) direction that they found is associated with chronic alcoholism as well as pathology of the anterior superior vermis of the cerebellum.

“This part of the brain is often disturbed in alcoholism, and lesions there, whether or not a result of alcoholism, can cause impairment in gait and balance,” she said. “It is interesting to note that while alcoholic men and women can quell their imbalance with stabilizing factors, alcoholic women do not necessarily improve to control levels.” Until more is known about improving this deficit, Sullivan suggested that people who are at risk utilized simple strategies to stabilize balance and to avert falls.

US researchers report finding that ghrelin, a hormone produced in the stomach that regulates appetite and how the body deposits fat, may be used to boost resistance to or slow the development of Parkinson’s disease.

The study is the work of Dr Tamas Horvath, chair and professor of comparative medicine and professor of neurobiology and obstetrics and gynecology at the Yale University School of Medicine, New Haven, Connecticut, and colleagues and was published earlier this month in The Journal of Neuroscience.

Parkinson’s disease is a neurodegenerative disorder where dopamine neurons in an area of the midbrain known as the substantia nigra, which is responsible for dopamine production, start to die off.

As less dopamine is produced, the symptoms become more severe, so that eventually people with the disease have difficulty walking, have restricted and delayed movements, get tremors in their head and limbs, lose their appetite, can’t eat properly, and have periods of immobility or “freezing”.

We already know that ghrelin targets the hypothalamus and affects appetite, food intake and how the body deposits fat. The authors wrote that ghrelin receptors at sites outside of the hypothalamus also “promote circuit activity associated with learning and memory, and reward seeking behavior”. And recent human studies have shown that body mass index (BMI), stored fat and diabetes are linked to Parkinson’s disease.

In this study, Horvath and colleagues discovered that ghrelin also protects the neurons that make dopamine.

“We also found that, in addition to its influence on appetite, ghrelin is responsible for direct activation of the brain’s dopamine cells,” said Horvath. He explained that because the hormone is made in the stomach, it circulates normally in the bloodstream, “so it could easily be used to boost resistance to Parkinson’s or it could be used to slow the development of the disease”.

For the study, which was supported by the Michael J Fox Foundation for Parkinson’s Research, Horvath and colleagues gave one group of mice extra ghrelin, and while another group were genetically engineered to lack the hormone and its receptor.

When compared to a group of control mice, the mice that had impaired ghrelin action in the brain had more dopamine loss.

The authors explained that the mice that were given extra ghrelin lost fewer substantia nigra pars compacta dopamine cells and showed “restricted striatal dopamine loss”, while the mice that were genetically engineered to lack the hormone and its receptors lost more substantia nigra pars compacta dopamine cells and showed “lowered striatal dopamine levels”. The effect in the genetically engineered mice was reversed when they switched the ghrelin receptor on.

They concluded that their study supports the idea that ghrelin could be a new therapeutic strategy to fight neurodegeneration, loss of appetite and body weight linked with Parkinson’s disease.

Horvath said they could see these results being applicable to humans because the ghrelin system is preserved through various species.

The researchers are now planning to find out how ghrelin levels differ between healthy people and people with Parkinsons disease, and whether changes in ghrelin levels might serve as a biomarker of disease susceptibility and development.

“Ghrelin Promotes and Protects Nigrostriatal Dopamine Function via a UCP2-Dependent Mitochondrial Mechanism.

Ghrelin, a hormone produced in the stomach, may be used to boost resistance to, or slow, the development of Parkinson’s disease, Yale School of Medicine researchers report in a study published in a recent issue of the Journal of Neuroscience.

Parkinson’s disease is caused by a degeneration of dopamine neurons in an area of the midbrain known as the substantia nigra, which is responsible for dopamine production. Reduced production of dopamine in late-stage Parkinson’s causes symptoms such as severe difficulty in walking, restricted movements, delays in moving, lack of appetite, difficulty eating, periods of remaining motionless (known as “freezing”) and head and limb tremors.

When the dopamine cells get sick and die, Parkinson’s can develop. Yale researcher Tamas Horvath and colleagues found that ghrelin is protective of the dopamine neurons. “We also found that, in addition to its influence on appetite, ghrelin is responsible for direct activation of the brain’s dopamine cells,” said Horvath, chair and professor of comparative medicine and professor of neurobiology and obstetrics & gynecology at Yale School of Medicine. “Because this hormone originates from the stomach, it is circulating normally in the body, so it could easily be used to boost resistance to Parkinson’s or it could be used to slow the development of the disease.”

Horvath and colleagues conducted the study in mice that received ghrelin supplementation and in mice that were deficient in ghrelin hormone and in the ghrelin receptor. When compared to controls, mice with impaired ghrelin action in the brain had more loss of dopamine. Horvath said the results could be easily translated to human use because the ghrelin system is preserved through various species.

Ghrelin was previously associated with the release of growth hormones, appetite, learning, memory, and with the reward circuitry of the brain that regulates food cravings. Recent human studies show that body mass index, stored fat and diabetes are linked to Parkinson’s disease. Past research also shows that obesity is a risk factor for neurodegeneration in mice.

In future work, Horvath and his team will try to determine ghrelin levels in both healthy individuals and Parkinson’s patients. He will also determine whether altered ghrelin levels might be a biomarker of disease development and vulnerability.