Posts tagged neuroscience

TAU researchers find chemicals in marijuana could help treat MS

Multiple sclerosis is an inflammatory disease in which the immune system attacks the nervous system. The result can be a wide range of debilitating motor, physical, and mental problems. No one knows why people get the disease or how to treat it.

In a new study published in the Journal of Neuroimmune Pharmacology, Drs. Ewa Kozela, Ana Juknat, Neta Rimmerman and Zvi Vogel of Tel Aviv University’s Dr. Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases and Sackler Faculty of Medicine demonstrate that some chemical compounds found in marijuana can help treat MS-like diseases in mice by preventing inflammation in the brain and spinal cord.

"Inflammation is part of the body’s natural immune response, but in cases like MS it gets out of hand," says Kozela. "Our study looks at how compounds isolated from marijuana can be used to regulate inflammation to protect the nervous system and its functions." Researchers from the Weizmann Institute of Science co-authored the study.

Mind-altering findings

Israel has a strong tradition of marijuana research. Israeli scientists Raphael Mechoulam and Yechiel Gaoni discovered THC, or tetrahydrocannabinol, in 1964, kick-starting the scientific study of the plant and its chemical constituents around the world. Since then, scientists have identified about 70 compounds — called cannabinoids — that are unique to cannabis and have interesting biological effects. In the 1990s, Prof. Vogel was among the first researchers to describe endocannabinoids, molecules that act like THC in the body.

Besides THC, the most plentiful and potent cannabinoid in marijuana is cannabidiol, or CBD. The TAU researchers are particularly interested in CBD, because it offers medicinal benefits without the controversial mind-altering effects of THC.

In a 2011 study, they showed that CBD helps treat MS-like symptoms in mice by preventing immune cells in their bodies from transforming and attacking the insulating covers of nerve cells in the spinal cord. After inducing an MS-like condition in mice — partially paralyzing their limbs — the researchers injected them with CBD. The mice responded by regaining movement, first twitching their tails and then beginning to walk without a limp. The researchers noted that the mice treated with CBD had much less inflammation in the spinal cord than their untreated counterparts.

High hopes for humans

In the latest study, the researchers set out to see if the known anti-inflammatory properties of CBD and THC could also be applied to the treatment of inflammation associated with MS — and if so, how. This time they turned to the immune system.

The researchers took immune cells isolated from paralyzed mice that specifically target and harm the brain and spinal cord, and treated them with either CBD or THC. In both cases, the immune cells produced fewer inflammatory molecules, particularly one called interleukin 17, or IL-17, which is strongly associated with MS and very harmful to nerve cells and their insulating covers. The researchers concluded that the presence of CBD or THC restrains the immune cells from triggering the production of inflammatory molecules and limits the molecules’ ability to reach and damage the brain and spinal cord.

Further research is needed to prove the effectiveness of cannabinoids in treating MS in humans, but there are reasons for hope, the researchers say. In many countries, CBD and THC are already prescribed for the treatment of MS symptoms, including pain and muscle stiffness.

"When used wisely, cannabis has huge potential," says Kozela, who previously studied opiates like morphine, derived from the poppy plant. "We’re just beginning to understand how it works."

(Source: aftau.org)

Researchers discover that an important clue to diagnosing Parkinson’s disease may lie just beneath the skin

Although Parkinson’s disease is the second most prevalent neurodegenerative disorder in the U.S., there are no standard clinical tests available to identify this widespread condition. As a result, Parkinson’s disease often goes unrecognized until late in its progression, when the brain’s affected neurons have already been destroyed and telltale motor symptoms such as tremor and rigidity have already appeared.

Now researchers from Beth Israel Deaconess Medical Center (BIDMC) have discovered that an important clue to diagnosing Parkinson’s may lie just beneath the skin.

In a study scheduled to appear in the October 29 print issue of the journal Neurology and currently published on-line, the investigators report that elevated levels of a protein called alpha-synuclein can be detected in the skin of Parkinson’s patients, findings that offer a possible biomarker to enable clinicians to identify and diagnose PD before the disease has reached an advanced stage.

Parkinson’s disease affects more than 1 million individuals throughout the U.S. Diagnosis is currently made through neurological history and examination, often by a patient’s primary care physician.

“Even the experts are wrong in diagnosing Parkinson’s disease a large percentage of the time,” says senior author Roy Freeman, MD, Director of the Autonomic and Peripheral Nerve Laboratory at BIDMC and Professor of Neurology at Harvard Medical School. “A reliable biomarker could help doctors in more accurately diagnosing Parkinson’s disease at an earlier stage and thereby offer patients therapies before the disease has progressed.”

Alpha-synuclein is a protein found throughout the nervous system. Although its function is unknown, it is the primary component of protein clumps known as Lewy bodies, which are considered the hallmark of Parkinson’s disease. There is accumulating evidence that the protein plays a role in Parkinson’s disease development.

“Alpha-synuclein deposition occurs early in the course of Parkinson’s disease and precedes the onset of clinical symptoms,” explains Freeman, who with his coauthors suspected that the protein was elevated in the skin’s structures with autonomic innervation.

“Symptoms related to the autonomic nervous system, including changes in bowel function, temperature regulation, and blood pressure control may antedate motor symptoms in Parkinson’s patients,” he explains. “Skin-related autonomic manifestations, including excessive and diminished sweating and changes in skin color and temperature, occur in almost two-thirds of patients with Parkinson’s disease. The skin can provide an accessible window to the nervous system and based on these clinical observations, we decided to test whether examination of the nerves in a skin biopsy could be used to identify a PD biomarker.”

To test this hypothesis, the research team enrolled 20 patients with Parkinson’s disease and 14 control subjects of similar age and gender. The participants underwent examinations, autonomic testing and skin biopsies in three locations on the leg. Alpha-synuclein deposition and density of cutaneous sensory, sudomotor and pilomotor nerve fibers were measured.

As predicted, their results showed that alpha-synuclein was increased in the cutaneous nerves supplying the sweat glands and pilomotor muscles in the Parkinson’s patients. Higher alpha-synuclein deposition in the nerves supplying the skin’s autonomic structures was associated with more advanced Parkinson’s disease and worsening autonomic function.

“There is a strong and unmet need for a biomarker for Parkinson’s disease,” says Freeman. “Alpha-synuclein deposition within the skin has the potential to provide a safe, accessible and repeatable biomarker. Our next steps will be to test whether this protein is present in the cutaneous nerves of individuals at risk for Parkinson’s disease, and whether measurement of alpha-synuclein deposition in the skin can differentiate Parkinson’s disease from other neurodegenerative disorders.”

(Source: newswise.com)

Babies learn how to anticipate touch while in the womb, according to new research.

Using 4-d scans psychologists at Durham and Lancaster universities found, for the first time, that fetuses were able to predict, rather than react to, their own hand movements towards their mouths as they entered the later stages of gestation compared to earlier in a pregnancy.

The Durham-led team of researchers said that the latest findings could improve understanding about babies, especially those born prematurely, their readiness to interact socially and their ability to calm themselves by sucking on their thumb or fingers.

They said the results could also be a potential indicator of how prepared babies are for feeding.

The researchers carried out a total of 60 scans of 15 healthy fetuses at monthly intervals between 24 weeks and 36 weeks gestation.

Fetuses in the earlier stage of gestation more frequently touched the upper part and sides of their heads.

As the fetuses matured they began to increasingly touch the lower, more sensitive, part of their faces including their mouths.

By 36 weeks a significantly higher proportion of fetuses were observed opening their mouths before touching them, suggesting that later in pregnancy they were able to anticipate that their hands were about to touch their mouths, rather than reacting to the touch of their hands, the researchers said.

Increased sensitivity around a fetus’ mouth at this later stage of pregnancy could mean that they have more “awareness” of mouth movement, they added.

Previous theories have suggested that movement in sequence could form the basis for the development of intention in fetuses.

The researchers said their findings could potentially be an indicator of healthy development, as arguably fetuses who are delayed in this development due to illness, such as growth restriction, might not show the same behaviour observed during the study.

The research, published in the journal Developmental Psychobiology, involved eight girls and seven boys and the researchers noticed no difference in behaviour between boys and girls.

Lead author Dr Nadja Reissland, in the Department of Psychology, at Durham University, said: “Increased touching of the lower part of the face and mouth in fetuses could be an indicator of brain development necessary for healthy development, including preparedness for social interaction, self-soothing and feeding.

“What we have observed are sequential events, which show maturation in the development of fetuses, which is the basis for life after birth.

“The findings could provide more information about when babies are ready to engage with their environment, especially if born prematurely.”

Brian Francis, Professor of Social Statistics at Lancaster, added: “This effect is likely to be evolutionally determined, preparing the child for life outside the womb. Building on these findings, future research could lead to more understanding about how the child is prepared prenatally for life, including their ability to engage with their social environment, regulate stimulation and being ready to take a breast or bottle.”

The study builds on previous research by Durham and Lancaster into fetal development. Earlier this year another of their studies showed that unborn babies practise facial expressions in the womb in what is thought to be preparation for communicating after birth.

And in 2012 Dr Reissland published research showing that unborn babies yawn in the womb, suggesting that yawning is a developmental process which could potentially give doctors another index of a fetus’ health.

It’s a question that has long fascinated and flummoxed those who study human behavior: From whence comes the impulse to dream? Are dreams generated from the brain’s “top” — the high-flying cortical structures that allow us to reason, perceive, act and remember? Or do they come from the brain’s “bottom” — the unheralded brainstem, which quietly oversees such basic bodily functions as respiration, heart rate, salivation and temperature control?

(Source: Los Angeles Times)

An inhibitory neuron type is found to specifically suppress the activation of other inhibitory neurons in cerebral cortex.

The cerebral cortex contains two major types of neurons: principal neurons that are excitatory and interneurons that are inhibitory, all interconnected within the same network. New research now reveals that one class of inhibitory neurons – called VIP interneurons — specializes in inhibiting other inhibitory neurons in multiple regions of cortex, and does so under specific behavioral conditions.

The new research finds that VIP interneurons, when activated, release principal cells from inhibition, thus boosting their responses. This provides an additional layer of control over cortical processing, much like a dimmer switch can fine-tune light levels.

The discovery was made by a team of neuroscientists at Cold Spring Harbor Laboratory (CSHL) led by Associate Professor Adam Kepecs, Ph.D. Their research, published online today in Nature, shows that neurons expressing vasoactive intestinal polypeptide, or VIP, provide disinhibition in the auditory cortex and the medial prefrontal cortex. 

The researchers used molecular tagging techniques developed by team member Z. Josh Huang, a CSHL Professor, to single out VIP-expressing neurons in the vast diversity of cortical neurons. This enabled Kepecs’ group, led by postdocs Hyun Jae Pi and Balazs Hangya, to employ advanced optogenetic techniques using color-coded laser light to specifically activate VIP neurons. The activity of the cells was monitored via electrophysiological recordings in behaving animals to study their function, and in vitro to probe their circuit properties.

These VIP neurons are long sought “disinhibitory” cells: they inhibit other classes of inhibitory neurons; but they do not directly cause excitation to occur in brain. Dr. Kepecs and colleagues propose that the disinhibitory control mediated by VIP neurons represents a fundamental “motif” in cerebral cortex.

The difference between neural excitation and disinhibition is akin to the difference between hitting the gas pedal and taking your foot off the breaks. Cells that specialize in releasing the brakes, Dr. Kepecs explains, provide the means for balancing between excitation and inhibition. Kepecs calls this function “gain modulation,” which brings to mind the fine control that a dimmer switch provides.

The team wondered when VIP neurons are activated during behavior. When, in other words, is the “cortical dimmer switch” engaged? To learn the answer the scientists recorded VIP neurons while mice were making simple decisions, discriminating between sounds of different pitches. When they made correct choices, the mice earned a drop of water; for incorrect choices, a mild puff of air. Surprisingly, the team found that in auditory cortex, a region involved in processing sounds, VIP neurons were activated by rewards and punishments. Thus these neurons appeared to mediate the impact of reinforcements and “turn up the lights” on principal cells, to use the dimmer-switch analogy.

“Linking specific neuronal types to well-defined behaviors has proved extremely difficult,” says Kepecs. These results, he says, potentially link the circuit-function of VIP neurons in gain control to an important behavioral function: learning.

(Source: cshl.edu)