A mechanism that may help explain Parkinson's and other neurological disorders.

Brain disorder suggests common mechanism may underlie many neurodegenerative diseases
A Mayo Clinic-led international consortium has found a mechanism that may help explain Parkinson's and other neurological disorders.
Studying just eight families worldwide, the international team of researchers have discovered a genetic defect that results in profound depression and parkinsonism in a disorder known as Perry syndrome. Although this syndrome is exceedingly rare, the mechanism implicated in it may help explain the origins of a variety of neurodegenerative disorders, such as Parkinson's and amyotrophic lateral sclerosis diseases, and even common depression and sleep disorders that are also hallmarks of the disorder, the researchers say.

In the study, to be published in the February issue of Nature Genetics (online January 11), the researchers report that people with Perry syndrome have mutations in a subunit of the dynactin complex (DCTN1; p150glued), which is essential to the movement of molecular "cargo" inside brain cells, or neurons. In this case, the mutations meant that the cargo was being driven on a "train" that essentially had faulty brakes. And because Perry syndrome resembles many other neurodegenerative diseases, the findings suggest breakdowns along the cell's interior transportation grid may be a common mechanism underlying neurodegeneration.

"Understanding why distinct neurons are selectively vulnerable to neurodegeneration in different brain disorders is one of the greatest puzzles in neuroscience," says the study's lead investigator, Matthew J. Farrer, Ph.D., a professor of neuroscience at Mayo Clinic. "These findings suggest that trafficking of specific cargoes inside brain cells may be a general problem in a variety of neurodegenerative diseases, depression, and other disorders."

"It points us to a unified theory of what is going wrong in many of them," says the study's senior author, Zbigniew K. Wszolek, M.D., professor of neurology at Mayo Clinic.

Molecules, vesicles and organelles within a cell are constantly carried via a network of crisscrossing microtubules that act like the tracks of an elaborate railroad system. Because, for the most part, neurons do not regenerate or divide as do other cells in the body, trafficking cargo efficiently over the lifetime of a neuron is fundamentally important, says Dr. Farrer.

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What are neurological disorders?
Neurological disorders are diseases of the central and peripheral nervous system. In other words, the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscles. These disorders include epilepsy, Alzheimer disease and other dementias, cerebrovascular diseases including stroke, migraine and other headache disorders, multiple sclerosis, Parkinson's disease, neuroinfections, brain tumours, traumatic disorders of the nervous system such as brain trauma, and neurological disorders as a result of malnutrition.

Mental disorders, on the other hand, are "psychiatric illnesses" or diseases which appear primarily as abnormalities of thought, feeling or behaviour, producing either distress or impairment of function.

Hundreds of million of people worldwide are affected by neurological disorders: For example, 50 million people have epilepsy; 62 million are affected by cerebrovascular disease; 326 million people suffer from migraine; 24 million are affected by Alzheimer disease and other dementias globally.

males and females Mosquitoes Create Harmonic Love Song just Before Mating

Graduate student and co-first author Lauren Cator records mosquito sound to study how mosquitoes that carry yellow and dengue fevers use sound in mating

That pesky buzz of a nearby mosquito is the sound of love, scientists have known for some time. But a new Cornell study reports that males and females flap their wings and change their tune to create a harmonic duet just before mating.
Cornell entomologists have discovered that male and female mosquitoes (Aedes aegypti), which can spread such diseases as yellow and dengue fevers, "interact acoustically with each other when the two are within earshot -- a few centimeters of each other," said Ron Hoy, professor of neurobiology and behavior.

The study is available online Jan. 8 and will be published in a February issue of Science, said Cornell associate professor of entomology and mosquito expert Laura Harrington, a co-senior author on the study with Hoy.

"The frequency at which males and females converge is a harmonic or multiple of their wing-beat frequencies, which is approximately 400 hertz [vibrations per second] for the female and 600 hertz for the male," said Hoy.

The mating duet, generated just before the couple mates on the fly, settles at around 1,200 hertz -- roughly an octave and a half above concert A (the pitch to which instruments are tuned -- the A that has a frequency of 440 hertz and is above middle C). "That is significantly higher than what was previously thought to be mosquitoes' upper hearing limit," he added.

Interestingly, the mosquitoes adjust the harmonic resonance of their thoracic box to produce a harmonic frequency that converges at a frequency that is the female's third harmonic (three times her fundamental frequency) and the male's second harmonic (two times his fundamental frequency). The study also is the first to definitively show that contrary to previous thought, female mosquitoes are not deaf.

To study mosquito mating calls, the researchers tethered mosquitoes and flew them past each other while recording the flight tones with a special microphone. Co-first author Benjamin Arthur, a postdoctoral researcher in Hoy's laboratory, placed electrodes in the mosquitoes' auditory organ in their antennae during playback to measure physiological responses of the mosquitoes to the sounds of potential mates.

The researchers hope that their work will provide new ways to better control of mosquito populations in places where yellow and dengue fevers are significant problems.

"By studying these flight tone signals, we may be able to determine what kind of information males and females consider important when choosing a mate," said co-first author Lauren Cator, a Cornell graduate student who works with Harrington. "This will allow us to release 'sexy' transgenic or sterilized males that will be able to successfully compete with wild populations."

Dengue fever affects 50 million people annually, and two-thirds of the world's population is at risk. In recent years, it has reached epidemic levels in Asia, South and Central America and Mexico, where the number of dengue cases has increased by more than 300 percent from year to year. No dengue vaccine is available, and no treatment exists beyond supportive care.

The study was funded by the U.S. Department of Agriculture and by a $19.7 million Foundation for the National Institutes of Health grant awarded to Harrington and a global team of scientists to cure dengue fever and control the mosquitoes that transmit the viruses that cause it.