Tag Archives: Neurons

The study exposed human olfactory and brain cells as targets of the original SARS-CoV-2 virus | Instant News


In a study published in iScience Jurnal, a research group from Switzerland showed that the receptor and entry gene for coronavirus 2 (SARS-CoV-2) severe acute respiratory syndrome is expressed in human olfactory nerve cells and the brain by observing key molecular players involved in the infection process.

The entry of SARS-CoV-2 which is the causative agent for the coronavirus disease pandemic (COVID-19) requires the use of a spike. glycoproteins to interact with the angiotensin-converting enzyme-2 (ACE2) receptor. Attached to the cell membrane are serine proteases TMPRSS2, which prioritizes glycoprotein spikes and facilitates viral entry.

As a result, the main target of the virus – namely the respiratory cells lining the respiratory tract – together express ACE2 and TMPRSS2. The nasal cavity also houses respiratory cells, but there is an area of ​​smell which is responsible for regulating the sense of smell.

And indeed, loss of smell is one of the causes symptoms of COVID-19; However, the notion that viruses can directly or indirectly affect the integrity and functioning of the sensory parts of the olfactory system is not new. Some viruses actually interfere with the neuroepithelium in various ways and often modify certain types of cells, including neurons.

But whether the olfactory dysfunction shown to be associated with SARS-CoV-2 infection originates from a generalized inflammatory process in the nasal cavity or from a targeted disorder of the olfactory neuroepithelium or olfactory bulb is unclear.

In this new paper, researchers from Switzerland (led by Dr. Leon Fodoulian of the University of Geneva) aim to investigate the distribution of the SARS-CoV-2 ACE2 receptor in human olfactory neuroepithelial cells, as well as in the brain.

Multidisciplinary methodological approach

This research effort was carried out using a multidisciplinary approach, based on its data and publicly available RNA-seq datasets, as well as immunohistochemical staining of mice and human tissue.

More specifically, the investigators have collected biopsies using endoscopic nasal surgery from four adult patients and then explored the potential for expression of ACE2 and TMPRSS2. Immunohistochemistry was then used to evaluate ACE2 expression in the human nasal cavity.

In their study, transcriptomic analysis of entire tissues and single cells of the human olfactory epithelium was pursued, and they have also explored two single-core RNA-seq data sets to assess ACE2 expression in the human brain precisely.

Sustentacular cells loaded with receptors

The results have revealed that a subset of olfactory support cells in the olfactory neuroepithelium (also known as support cells involved in odor transformation and xenobiotic metabolism) express ACE2, but not olfactory sensory neurons.

“In mice, where the olfactory mucosa is well structured both in terms of the pseudo layer and in terms of its very tight separation from the respiratory epithelium, we observed (similar to humans) clear ACE2 expression at the apical boundaries of the support cells”, explain the study authors.

However, this distribution is not homogeneous because ACE2 is observed in cells that are located very dorsally but completely absent in the more ventral zone of the olfactory neuroepithelium.

However, these cells were also found to express TMPRSS2, and the researchers also revealed ACE2 expression in a subset of brain cell types – including nerve cells and non-neurons.

Credible link with anosmia

In short, this study has shown that respiratory cells are not the only players in contact with the outside world which stores the molecular keys involved in the entry of SARS-CoV-2 in the nose. Sustentacular cells, located at the interface between the central nervous system and the olfactory cavity, have the same properties.

But what is the likelihood that the co-expression of ACE2 in olfactory-supporting cells and its direct connection to the brain is the underlying cause of SARS-CoV-2-induced anosmia?

“Taken together, and despite the fact that one cannot exclude inflammation and infection of other types of non-neuronal cells in the olfactory neuroepithelium as the origin of SARS-CoV-2- induced anosmia, the relationship between the means of entry of viral molecules is revealed by the olfactory support and SARS-CoV-2-induced chemosensory changes appear to be quite credible “, the study authors concluded.

However, the existence of a wide variety of neuronal and non-neuronal cell populations that express ACE2 in the human brain is a research interest that needs to be pursued, with possible practical applications in the future.

.



image source

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.

.



image source

Neurologists on the map touch the gatekeeper of the brain in unprecedented detail | Instant News


Many people with autism experience sensory hypersensitivity, attention deficit, sleep disorders. One area of the brain that were involved in these symptoms of the thalamic reticular nucleus (ryat), which is believed to acts as a gatekeeper for sensory information entering the cortex.

A group of researchers from mit and the broad Institute of MIT and Harvard, is now visible in unprecedented detail TIN, showing that the region contains two different subnets of neurons with different functions. The obtained results have more to offer researchers specific targets for drug development that could facilitate some of the senses, sleep and attention symptoms of autism, says Guoping Feng, one of the leaders of the research team.

The idea is that you can very specifically one group of neurons without affecting the whole brain, and other cognitive functions”.

Guoping Feng, the James and Patricia Poitras Professor of neuroscience at MIT and a member of the Institute of mit McGovern Institute for brain research

Feng; SMA-Fu, Deputy Director of neurobiology in the center of the broad Institute of psychiatric research, Stanley; and Joshua Levin, senior group leader at broad Institute, senior author of the study, which appears today in Nature. Leading the report’s authors, former post-doctoral research fellowship at MIT, Yinqing Li, a former postdoc of the broad Institute Violeta Lopez-Huerta, and a wide researcher of the Institute of Xian Adiconis.

Some populations

When you receive sensory information from the eyes, ears and other sensory organs to our brain, it goes first to the thalamus, which then relays it to the cortex for higher level processing. The disadvantages of these thalamo-cortical circuit may lead to attention deficit, hypersensitivity to noise and other stimuli, and sleep problems.

One of the main ways, which controls the flow of information from the thalamus and cortex TRN, which is responsible for blocking distracting stimuli. In 2016, Feng and MIT associate Professor Michael Halassa, who is also the author of the new Nature the paper found that the loss under the Ptchd1 gene significantly affect the function of the RNN. In boys, the loss of this gene, which is carried on the X chromosome, may lead to attention deficit, hyperactivity, aggression, mental retardation and autism spectrum disorders.

In this study, the researchers found that when the Gene Ptchd1 was knocked out in mice, animals showed many of the same behavioral defects seen in humans. When he was knocked out only in TRN, the mice showed only hyperactivity, attention deficit, sleep disturbances, assuming that the BCH is responsible for these symptoms.

In the new study, the researchers wanted to try to learn more about specific types of neurons found in the BCH, in the hope of finding new methods of treating hyperactivity and attention deficit. Currently, these symptoms are most commonly treated with stimulants, such as ritalin, which have a wide impact on the entire brain.

“Our goal was to find a particular part, to modulate functions of the thalamo-cortical output and link it to neurological development,” says Feng. “We decided to try using single-cell technology to analyze what types of cells are there and what genes are expressed. There are certain genes that are amenable to therapy with drugs that are included as a target?”

To explore this possibility, the researchers sequenced the messenger RNA molecules found in the neurons of the RNN, which reveals the genes that are expressed in these cells. This allowed them to identify several hundred genes that can be used to differentiate the cells into two subpopulations, based on how strongly they Express certain genes.

They found that one of these cell populations is at the core of TIN, and the other forms a very thin layer around the nucleus. These two populations also form connections of various parts of the thalamus, the researchers found. On the basis of these compounds, the researchers suggest that cells mainly involved in transmission of sensory information to the cortex when cells in the outer layer appear to help to coordinate information across different senses, such as sight and hearing.

“Targets amenable to therapy with drugs included”

Now scientists plan to study the different roles that these two populations of neurons can have different neurological symptoms, including attention deficit, hypersensitivity, and sleep disturbance. Using genetic and optogenetic methods, they hope to determine the effects of activation or inhibition of different TIN cell types, or genes that are expressed in those cells.

“This may help us in the future to develop specific tasks, amenable to therapy with preparations that have the potential to modulate different functions,” says Feng. “Thalamo-cortical circuits control many different things such as sensory perception, sleep, attention, and cognition, and it may well be that they can be targeted more specifically.”

This approach can also be useful for treating disorders of attention or sensitivity, even when not caused by defects in the function of TIN, say the researchers.

“Trn-target where if you can improve its function, you may be able to fix the problems caused by violations of thalamo-cortical circuits,” says Feng. “Of course, we are far from development of any kind of treatment, but the potential that we can use single-cell technology to not only understand how the brain organizes itself, but also how brain function can be separated, allowing to identify more specific targets that modulate specific functions.”

.



image source

Research finds that specific brain cells trigger sugar consumption and cravings | Instant News


New research has identified specific brain cells that control how much sugar you eat and how hungry you are for sweet foods.

Most people enjoy sweets from time to time. However, unchecked “sweets” can lead to excessive consumption of sugary foods and chronic health problems such as obesity and type 2 diabetes. Understanding the biological mechanisms that control sugar intake and preference for sweetness may have important implications for controlling and preventing these health problems.

The new research is led by Dr. Matthew Potthoff, associate professor of neuroscience and pharmacology at Carver University in Iowa, and Dr. Matthew Gillum at Copenhagen University in Denmark. The research focuses on the action of a hormone called fibroblast growth. Factor 21 (FGF21). This hormone is known to play a role in energy balance, weight control and insulin sensitivity.

This is the first study to truly identify where this hormone works in the brain, and provides very cool insights into how to regulate sugar intake. “

Matthew Potthoff, a member of the Eagle Diabetes Brotherhood Research Center at UI and the Iowa Neuroscience Institute

Potthoff and his colleagues previously discovered that FGF21 is made in the liver in response to elevated sugar levels and plays a role in the brain to suppress sugar intake and preference for sweetness.

Based on this discovery, the team now shows for the first time which brain cells respond to FGF21 signaling and how this interaction helps regulate sugar intake and sweetness preferences. The study was published in the journal Cell metabolism, Also revealed how hormones mediate their effects.

Although FGF21 is known to function in the brain, because hormone receptors are expressed at very low levels, it is difficult to “see”, so determining the exact cellular target becomes complicated. Using various techniques, the researchers were able to accurately identify which cells express the FGF21 receptor. By studying these cells, studies have shown that FGF21 targets glutamatergic neurons in the brain to reduce sugar intake and sweet taste preference. The researchers also showed that the effect of FGF21 on specific neurons in the hypothalamus of the peritoneum reduces sugar intake by enhancing the sensitivity of neurons to glucose.

Several drugs based on modified forms of FGF21 have been tested as treatments for obesity and diabetes. The new discovery may cause the new drug to more precisely target the different behaviors controlled by FGF21, which may help control how much sugar a person eats.

Resources:

Journal reference:

Jensen-Cody, so, Wait. (2020) FGF21 signaling to the hypothalamus glutamatergic neurons in the hypothalamus inhibits carbohydrate intake. Cell metabolism. doi.org/10.1016/j.cmet.2020.06.008.

.



image source

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.

.



image source