Tag Archives: nervous system

The study explains how to rebuild the neurons inside fat to increase the calorie burning capacity | Instant News

A previous study suggested that you can lose weight, eat less or move more. However, despite studying it for many decades, the biology underlying this equation remains mysterious.

What really ignites the breakdown of fat molecules nerves embedded in fat, and new research now suggests that these fat burning of neurons previously unrecognized powers. If they get the right signal, they have the amazing ability to grow. This signal is the hormone leptin, which is secreted by fat cells.

In experiments with mice, the results of which are published in the journal Nature, the researchers found that, as a rule, a dense network of nerve fibers in adipose tissue is reduced in the absence of leptin and increases the hormone as a drug. These changes were shown to influence the ability of animals to burn energy stored in fat.

“While the architecture of the nervous system can significantly change how a young animal develops, we did not expect to find in this deep level of neural plasticity in an adult,” says Jeffrey M. Friedman, molecular geneticist of the Rockefeller University.

If confirmed in humans, this information can advance research on obesity and related diseases, and potentially opens the way for the development of new therapies, which target neurons in the adipose tissue.

The team began looking at what happens to mice that do not produce leptin on their own, and how they react when you speak with him.

Found in Friedman’s laboratory in 1994, the hormone relay signals from adipose tissue and the brain, allowing the nervous system to curb appetite and increase energy expenditure to control body weight. When mice are genetically engineered to stop the production of leptin, they grow three times heavier than a normal mouse. They eat more, move less, and can survive in what should be tolerated the cold because their body cannot properly use fat to generate heat.

Giving these mice leptin doses, however, and they quickly begin to eat less and move more. But when the researchers processed them longer, within two weeks, more profound changes have occurred: the animals began to break down white fat, which stores unused calories at a normal level and regained the ability to use another form of fat, brown fat, to produce heat.

It was slower than the changes that interested the research team, including first authors on the nature paper, Putianqi Wang, a graduate student in the lab, and Ken H. Luo, postdoctoral fellow. They suspect that changes of neurons outside of the brain-those that are distributed in fat … might explain why this part of the response to leptin it took some time.

Using the imaging technique, developed in the laboratories of the Rockefeller and Paul Cohen to visualize the nerves inside the body fat, researchers have traced the influence of leptin on fat-built-in neurons of the brain the hypothalamus region. Hence, they are found contributing to the growth of Leptin that message goes through the spinal cord back to the neurons to fat.

“This work is the first example of how leptin can regulate the presence of neurons in adipose tissue, white and brown,” added Cohen.

In this way, fat seems to be telling the brain how much nerve supply it needs to function properly. “Fat is indirectly controlled by its own innervation and hence function,” says Friedman. “It is an exquisite feedback loop”.

Future research will analyze the role of this pathway in human obesity and may provide a new approach to therapy. Most of the obese people produce high levels of leptin and showed a decrease of response to hormone injection, suggesting that their brains are resistant to the hormone. Thus, the bypass resistance leptin may have a therapeutic effect for these patients.

“In the new study, we see that similar to animals lacking leptin, obese leptin-resistant animals also show a low-fat innervation. Therefore, we assume that directly stimulating the nerves that Innervate fat and restoring the normal ability to use stored fat can create new opportunities for the treatment of obesity,” said Friedman.


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How COVID-19 affects the nervous system | Instant News

A new paper published in the journal JAMA Neurology in May 2020 discussed the presentation and complications of COVID-19 with respect to the nervous system.

The COVID-19 pandemic has caused hundreds of thousands of cases of severe pneumonia and respiratory disorders, in 188 countries and regions in the world. The causative agent, SARS-CoV-2, is a new coronavirus, with well-recognized lung complications. However, evidence is increasing that the virus also affects other organs, such as the nervous system and heart.

The Coronaviruses: A Glimpse

That corona virus is a group of large spread RNA viruses that infect animals and humans. Human infections are known to be caused by 7 coronaviruses, namely human coronavirus (HCoV) –229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43, MERS-CoV, SARS-CoV-1, and SARS-CoV-2.

Among these, the last three are known to cause severe human disease. While HCoV is more associated with respiratory manifestations, three of them are known to infect neurons: HCoV-229E, HCoV-OC43, and SARS-CoV-1.

Current research aims to contribute to the knowledge of the SARS-CoV-2 neurotropism, as well as post-infectious neurological complications. This virus infects humans through ACE2 receptors in various tissues, including airway epithelium, kidney cells, small intestine, proper lung tissue, and endothelial cells.

Because endothelium is found in blood vessels throughout the body, this offers a potential route for CoV to be localized in the brain. In addition, a recent report shows that ACE2 is also found in brain neurons, astrocytes, and oligodendrocytes, especially in areas such as substantia nigra, ventricles, middle temporal gyrus, and olfactory bulb.

Interestingly, ACE2 in neuron tissue is expressed not only on the surface but also in the cytoplasm. This finding could imply that SARS-CoV-2 can infect neuronal and glial cells in all parts of the central nervous system.

How does neuroinvasion occur with SARS-CoV-2?

Current knowledge indicates the possibility of nerve cell virus invasion by several mechanisms. These include the transfer of viruses across synapses of infected cells, entering the brain through the olfactory nerve, infection of endothelial blood vessels, and migration of infected white blood cells across the blood-brain barrier (BBB).

The corona virus has been shown to spread back along the nerves from the edge of the peripheral nerves, across synapses, and thus into the brain, in several small animal studies. This is facilitated by a pathway for endocytosis or exocytosis between motor cortex neurons, and other secretory vesicular pathways between neurons and satellite cells.

Axonal transport occurs rapidly using axonal microtubules, which allow the virus to reach the body of neuron cells with a retrograde version of this mechanism.

The possibility of spreading the olfactory route is marked by the occurrence of isolated anosmia and age. In such cases, the virus can pass through the latticed plate to enter the central nervous system (CNS) of the nose. However, more recent unpublished research shows that olfactory neurons lack ACE2, whereas cells in the olfactory epithelium do so. This could mean that a viral injury to the olfactory epithelium, and not the olfactory neuron, is responsible for anosmia, but further studies will be needed to confirm this.

Cross the BBB

This virus can also pass through the BBB through two separate mechanisms. In the first case, infected vascular endothelial cells can move the virus across blood vessels to neurons. Once there, the virus can start to bud and infect more cells.

The second mechanism is through infected white blood cells that pass through the BBB – a mechanism called Trojan horse, which is famous for its role in HIV. Inflamed BBB allows the entry of immune cells and cytokines, and even, possibly, viral particles into the brain. T-lymphocytes, however, do not allow viruses to replicate even though they can be infected.

Neurological features of COVID-19

From limited data on neurological manifestations related to COVID-19, it is clear that headaches, anosmia, and age are among the most common symptoms. However, other findings include stroke and an abnormal state of consciousness.

While headaches occur in up to one third of confirmed cases, anosmia or age shows a much more varied prevalence. In Italy, about one fifth of cases show this symptom, while almost 90% of patients in Germany have such symptoms.

The researchers said, “Given the reports of anosmia that appear as early symptoms of COVID-19, specific testing for anosmia can offer the potential for early detection of COVID-19 infection.”

Impaired consciousness can occur in up to 37% of patients, due to various mechanisms such as infection and direct brain injury, metabolic-toxic encephalopathy, and demyelinating disease. Encephalitis has not been documented as a result of COVID-19.

Toxic-metabolic encephalopathy can occur due to a number of disorders of metabolic and endocrine function. These include electrolyte and mineral imbalances, kidney disorders, and cytokine storms, hypo or hyperglycemia, and liver dysfunction. Patients who are elderly, ill, or already have symptoms of dementia, or are malnourished, are at higher risk for this condition.

Less common neurological complications include Guillain-Barre syndrome, which is a post-viral acute inflammatory demyelinating disease, and cerebrovascular events, including stroke.

Is COVID-19 Therapy Related to Neurological Manifestations?

Nowadays, many different drugs are used to treat this condition.

Chloroquine and hydroxychloroquine, for example, can cause psychosis, peripheral neuropathy, and the latter can worsen the symptoms of myasthenia gravis. Tocilizumab, an IL-6 blocker, is intended to reduce excessive cytokine release that occurs in severe inflammation. Although admission to CNS is limited, it can sometimes cause headaches and dizziness.

Precautions for COVID-19 Patients with Neurological Conditions

If a patient already has a neurological condition that requires special treatment, they tend to be at higher risk for COVID-19, due to existing lung, heart, or liver conditions, having kidney disease (dialysis), if they are overweight, or at immunosuppressive drugs. Also, it is likely that they may be in nursing homes, where many countries have reported severe outbreaks.

This study concludes: “Doctors must continue to monitor patients closely for neurological diseases. Early detection of neurological deficits can lead to improved clinical outcomes and better treatment algorithms. “

Journal reference:

  • Zubair, A. S. et al. (2020). Neuropathogenesis and Neurological Manifestations of Coronavirus in the Coronavirus Era 2019: Overview. JAMA Neurology. doi: 10.1001 / jamaneurol.2020.2065.


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Neurobiologists Discover Effective Pain Relief Centers in the Brain | Instant News

DURHAM, N.C. – Duke University research team has found a small area of ​​the brain in mice that can control animal pain.

Somewhat unexpectedly, this brain center kills pain, not life. It is also located in an area where some people will think of looking for an anti-pain center, the amygdala, which is often considered a home for emotions and negative responses, such as fight or flight responses and general anxiety.

“People believe there is a central place for pain relief, that’s why placebos work,” said senior author Fan Wang, professor of neurobiology Morris N. Broad Distinguished of neurobiology at the School of Medicine. “The question is where in the brain is the center that can kill pain.”

“Most of the previous studies focused on which areas were ACTIVE by pain,” Wang said. “But there are so many areas that process pain, you have to turn off everything to stop the pain. Even though this one center can kill pain by itself.”

This work is a follow-up to previous research in Wang’s laboratory looking at neurons that are activated, not suppressed, by general anesthesia. In a 2019 study, they found that general anesthesia promotes slow wave sleep by activating the brain’s supraoptic nucleus. But sleep and pain are separate, important clues that lead to new findings, which appear online May 18 in Nature Neuroscience.

The researchers found that general anesthesia also activates specific subset of inhibitory neurons in the central amygdala, which they call CeAga neurons (CeA stands for central amygdala; does not indicate activation by general anesthesia). Rats have a relatively larger central amygdala than humans, but Wang says he has no reason to think we have a different system for controlling pain.

Using technology pioneered by Wang’s lab to track the pathways of neurons that are activated in mice, the team found that CeAga is connected to many different areas of the brain, “which is surprising,” Wang said.

By giving mice a mild pain stimulus, the researchers could map out all areas of the brain that activated pain. They found that at least 16 brain centers known to process sensory or emotional aspects of pain received inhibitory input from CeAga.

“Pain is a complicated brain response,” Wang said. “This involves sensory, emotional, and autonomic (unconscious nervous system) discrimination. Treating pain by reducing all these brain processes in many areas is very difficult to achieve. But activating a key node that naturally sends inhibitory signals to this pain processing area will be stronger. “

Using a technology called optogenetics, which uses light to activate small populations of cells in the brain, the researchers found they could kill the self-care behavior that mice exhibit when they feel uncomfortable by activating CeAga neurons. The behavior of licking or rubbing the face is “completely erased” once the light is turned on to activate the anti-pain center.

“Very drastic,” Wang said. “They immediately stop licking and rubbing.”

When scientists suppressed the activity of CeAga’s neurons, mice responded as if temporary insults became intense or painful again. They also found that low-dose ketamine, an anesthetic that allows sensation but inhibits pain, activates the CeAga center and will not work without it.

Now researchers will look for a drug that can only activate these cells to suppress pain as a potential pain killer in the future, Wang said.

“Another thing that we are trying to do is (transcriptome) sorting out of these cells,” he said. The researchers hope to find genes for rare or unique cell surface receptors among specialized cells that will allow very specific drugs to activate these neurons and relieve pain.

This research was supported by the National Institutes of Health (DP1MH103908, R01 DE029342, R01 NS109947, R01 DE027454), Holland-Trice Scholar Award, the W.M. Keck Foundation, and predoctoral fellowship from the National Science Foundation.

CITATION: “General Anesthesia Activates Powerful Central Pain-Suppressing Circuits in Amygdala,” Thuy Hua, Bin Chen, Dongye Lu, Katsuyasu Sakurai, Shengli Zhao, Bao-Xia Han, Kim Jiwoo, Luping Yin, Yong Chen, Jinghao Lu, Fan Wang . Nature Neuroscience, May 18, 2020. DOI: 10.1038 / s41593-020-0632-8


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