How childhood viral infections may later drive multiple sclerosis

Childhood viral infections that reach the brain may prime it for the development of autoimmune conditions, such as multiple sclerosis, later in life — this is what a recent study that scientists conducted in mice seems to suggest.

Recent research has shown that multiple sclerosis (MS) is the most common neurological autoimmune condition among young adults worldwide, with 2,221,188 prevalent cases of MS in 2016 alone.

This condition can cause problems with movement, balance, coordination, and even vision, alongside fatigue and other symptoms.

Despite the fact that MS can be debilitating, and that it affects such a large number of people worldwide, scientists are still unsure what causes it.

Now, a team of researchers from the University of Geneva (UNIGE) and the Geneva University Hospitals in Switzerland are proposing a new theory that viral infections during childhood could reach the brain and render the development of an autoimmune condition more likely later in life.

The researchers support this theory through evidence from a study of mouse models of MS, and they report their findings in the journal Science Translational Medicine.

"We asked ourselves whether brain viral infections that could be contracted in early childhood were among the possible causes," explains study co-author Doron Merkler, who is an associate professor in the Department of Pathology and Immunology at UNIGE's Faculty of Medicine.

"But these transient infections may, under certain circumstances, leave a local footprint, an inflammatory signature, in the brain," he adds, pointing out that this "mark" might be a factor in MS.

Brain lesions after a viral infection

In the current study, Merkler and team first induced a transient viral infection (an attenuated strain of the lymphocytic choriomenigitis virus) in two groups of mice — one of adult rodents, and another of very young ones.

"In both cases, the mice showed no signs of the disease and eliminated the infection within a week with a similar anti-viral immune response," notes study co-author Karin Steinbach, Ph.D.

For the second step of the research, the investigators allowed all the mice to age. Then, they transferred self-reactive cells to the mice. This type of cell, the researchers explain, can impact brain structure, and some scientists also believe that they contribute to MS.

"These self-reactive cells are present in most of us, but do not necessarily induce a disease, since they are controlled by different regulatory mechanisms and usually don't have access to the brain," Steinbach explains.

This was certainly true for the mice that had had the viral infection in adulthood. In these rodents, the transferred self-reactive cells did not reach the brain.

However, the mice that had had a viral infection early in their life developed brain lesions — in their case, the self-reactive cells managed to infiltrate the brain and affect it. Moreover, when they entered the brain, they went straight to the area where the viral infection had been present.

When they studied the brains of the mice that had had the viral infection as pups, the investigators found that an abnormal number of brain-resident memory T cells, which are a certain type of immune cells, had accumulated in the cortex.

"Under normal circumstances, these cells are distributed throughout the brain, ready to protect it in case of a viral attack. But here, the cells accumulate in surplus at the exact spot of the infantile infection in the brain," notes Merkler.

In the mice, brain-resident memory T cells produced a molecule that attracted self-reactive cells, which helped them to gain access to the brain, causing lesions.

 Source: Medical News Today

When and why is pain pleasurable?

Many people think of pain and sex as deeply incompatible. After all, sex is all about pleasure, and pain has nothing to do with that, right? Well, for some individuals, pain and pleasure can sometimes overlap in a sexual context, but how come? Continue reading this Spotlight feature to find out.

The relationship between pain and sexual pleasure has lit up the imaginations of many writers and artists, with its undertones of forbidden, mischievous enjoyment.

In 1954, the erotic novel Story of O by Anne Desclos (pen name Pauline Réage) caused a stir in France with its explicit references to bondage and discipline, dominance and submission, sadism and masochism — an array of sexual practices referred to as BDSM, for short.

Recently, the series Fifty Shades of Grey by E. L. James has sold millions of copies worldwide, fuelling the erotic fantasies of its readers.

Still, practices that involve an overlap of pain and pleasure are often shrouded in mystery and mythologized, and people who admit to engaging in rough play in the bedroom often face stigma and unwanted attention.

So what happens when an individual finds pleasure in pain during foreplay or sexual intercourse? Why is pain pleasurable for them, and are there any risks when it comes to engaging in rough play?

In this Spotlight feature, we explain why physical pain can sometimes be a source of pleasure, looking at both physiological and psychological explanations.

Also, we look at possible side effects of rough play and how to cope with them and investigate when the overlap of pain and pleasure is not healthful.

Physical pain as a source of pleasure

First of all, a word of warning: Unless a person is specifically interested in experiencing painful sensations as part of their sexual gratification, sex should not be painful for the people engaging in it.

People may experience pain during intercourse for various health-related reasons, including conditions such as vaginismus, injuries or infections of the vulva or vagina, and injuries or infections of the penis or testicles.

If you experience unwanted pain or any other discomfort in your genitals during sex, it is best to speak to a healthcare professional about it.

Healthy, mutually consenting adults sometimes seek to experience painful sensations as an "enhancer" of sexual pleasure and arousal. This can be as part of BDSM practices or simply an occasional kink to spice up one's sex life.

But how can pain ever be pleasurable? According to evolutionary theory, for humans and other mammals, pain functions largely as a warning system, denoting the danger of a physical threat. For instance, getting burned or scalded hurts, and this discourages us from stepping into a fire and getting burned to a crisp or drinking boiling water and damaging our bodies irreversibly.

Yet, physiologically speaking, pain and pleasure have more in common than one might think. Research has shown that sensations of pain and pleasure activate the same neural mechanismsin the brain.

Pleasure and pain are both tied to the interacting dopamine and opioid systems in the brain, which regulate neurotransmitters that are involved in reward- or motivation-driven behaviors, which include eating, drinking, and sex.

In terms of brain regions, both pleasure and pain seem to activate the nucleus accumbens, the pallidum, and the amygdala, which are involved in the brain's reward system, regulating motivation-driven behaviors.

Thus, the "high" experienced by people who find painful sensations sexually arousing is similar to that experienced by athletes as they push their bodies to the limit.

Source: Medical News Today

Obesity: How diet changes the brain and promotes overeating

Scientists have implicated specific neurons in the lateral hypothalamic area, a region involved in survival mechanisms such as food intake, in signaling to the brain when to stop eating. This mechanism is impaired in obese mice.

How does obesity trick the brain into sending a signal that says to keep on eating?

Obesity is a worldwide problem, with the World Health Organization (WHO) estimating that 650 million people across the globe were obese in 2016.

Many experts point the finger at overeating and a sedentary lifestyle as the root causes of the obesity epidemic.

However, any action that we take has consequences at the molecular level, and experts know little detail about how our brains behave as the readings on the scales slowly go up.

Scientists from the Department of Psychiatry at the University of North Carolina in Chapel Hill, along with collaborators in the United States, Sweden, and the United Kingdom, sought to unravel the molecular pathways at play in the brains of mice with obesity.

Garrett Stuber, a professor of neurobiology who has now moved to the Center for the Neurobiology of Addiction, Pain, and Emotion at the University of Washington in Seattle, is the senior author of the team's results, which feature in the journal Science.

Identifying the 'brake on feeding'

Stuber and his collaborators study a specific area of the brain called the lateral hypothalamic area (LHA).

"The LHA has long been known to play [a] role in promoting feeding behavior, but the exact cell types that contribute to feeding within this brain structure are not well-defined," explained Stuber about his research to Medical News Today.

Analyzing gene expression in individual cells in the LHA in obese mice and comparing it to that in normal mice, the team found prominent changes in vesicular glutamate transporter type-2 (Vglut2)–expressing neurons. These cells use glutamate as their fast-acting neurotransmitter.

However, changes in gene expression do not necessarily equate to changes in function.

Stuber dug deeper and used a combination of techniques to visualize individual LHA^Vglut2 neurons when the team gave mice sucrose, a common sugar comprising glucose and fructose.

The researchers found that sucrose consumption resulted in the cells' activation. However, the response was nuanced. Mice that were not very hungry showed strong activation of their LHA^Vglut2neurons, whereas those that had fasted for 24 hours had an attenuated response.

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Stuber and his colleagues, therefore, suggest that LHA^Vglut2 neurons play a role in the suppression of feeding by telling our brain when to stop eating. They call this the "brake on feeding."

"We hypothesize that the excitatory LHA^Vglut2 signal represents the activation of a brake on feeding to suppress further food intake," they write.

Next, the team investigated how obesity affects the activity of these cells in mice that ate a high fat diet for 12 weeks to induce obesity.

"Whereas LHA^Vglut2 neurons from control mice maintained their responsivity to sucrose consumption, LHA^Vglut2 neurons from [the high fat diet] mice became progressively less responsive to sucrose consumption and less active at rest," the team writes in the study paper.

In other words, the neurons did not send such a strong "stop eating" signal to the brain when the mice consumed sugar or when the mice were resting. Instead, the animals overate and developed obesity.

Obesity 'impairs break on food intake'

When MNT asked whether he was surprised to see such a stunted response by the cells, Stuber explained, "Yes, the imaging results, which show that LHA glutamate cells are downregulated by high fat diet exposure (our experimental model of obesity) was surprising to us."

"When these neurons are activated, mice halt sucrose licking and avoid locations paired with LHA^Vglut2 stimulation. Thus, activation of LHA^Vglut2 neurons may serve as a brake on feeding," comments Stephanie Borgland, a professor at the Hotchkiss Brain Institute at the University of Calgary in Canada, in an accompanying Perspective article in Science.

"Given that activation of these neurons also leads to escape and avoidance behaviors, these neurons may be involved in the switch from foraging to escaping to promote survival, which is consistent with other homeostatic functions of the hypothalamus."

Source: Medical News Today

All you need to know about neurons

Neurons are responsible for carrying information throughout the human body. Using electrical and chemical signals, they help coordinate all of the necessary functions of life. In this article, we explain what neurons are and how they work.

In short, our nervous systems detect what is going on around us and inside of us; they decide how we should act, alter the state of internal organs (heart rate changes, for instance), and allows us to think about and remember what is going on. To do this, it relies on a sophisticated network — neurons.

It has been estimated that there are around 86 billion neurons in the brain; to reach this huge target, a developing fetus must create around 250,000 neurons per minute.

Each neuron is connected to another 1,000 neurons, creating an incredibly complex network of communication. Neurons are considered the basic units of the nervous system.

Because they are

Neurons, sometimes called nerve cells, make up around 10 percent of the brain; the rest consists of glial cells and astrocytes that support and nourish neurons.

What do neurons look like?

Neurons can only be seen using a microscope and can be split into three parts:

Soma (cell body) — this portion of the neuron receives information. It contains the cell's nucleus.

Dendrites — these thin filaments carry information from other neurons to the soma. They are the "input" part of the cell.

Axon — this long projection carries information from the soma and sends it off to other cells. This is the "output" part of the cell. It normally ends with a number of synapses connecting to the dendrites of other neurons.

Both dendrites and axons are sometimes referred to as nerve fibers.

Axons vary in length a great deal. Some can be tiny, whereas others can be over 1 meter long. The longest axon is called the dorsal root ganglion (DRG), a cluster of nerve cell bodies that carries information from the skin to the brain. Some of the axons in the DRG travel from the toes to the brain stem — up to 2 meters in a tall person.

Types of neurons

Neurons can be split into types in different ways, for instance, by connection or function.

Connection

Efferent neurons — these take messages from the central nervous system (brain and spinal cord) and deliver them to cells in other parts of the body.

Afferent neurons — take messages from the rest of the body and deliver them to the central nervous system (CNS).

Interneurons — these relay messages between neurons in the CNS.

Function

Sensory — carry signals from the senses to the CNS.

Relay — carry signals from one place to another within the CNS.

Motor — carry signals from the CNS to muscles.

How do neurons carry a message?

If a neuron receives a large number of inputs from other neurons, these signals add up until they exceed a particular threshold.

Once this threshold is exceeded, the neuron is triggered to send an impulse along its axon — this is called an action potential.

An action potential is created by the movement of electrically charged atoms (ions) across the axon's membrane.

Neurons at rest are more negatively charged than the fluid that surrounds them; this is referred to as the membrane potential. It is usually -70 millivolts (mV).

 Source: Medical News Today

Are our brains addicted to information?

According to new research, human brains really are hungry for information, and this hunger can devolve into unhealthful snacking-like behaviors now that we have unfettered access to random information.

Humans are naturally curious beings. We constantly seek to learn, explore, and understand. However, curiosity may not always be a positive feature.

The popular saying, "Curiosity killed the cat" refers to seeking knowledge to the point of putting oneself in danger.

Although not exactly in the sense that this saying connotes, humans' modern-day compulsion to seek information can have negative effects.

As we scroll greedily through social media or peruse random, bite-sized articles about nothing in particular, we may be feeding the equivalent of empty calories to our brains.

Or, to put it a different way, our brains may be addicted to unvaluable information on which we snack insatiably.

Why is this the case? In a new study, two researchers — from the Helen Wills Neuroscience Institute and the Haas School of Business, at the University of California, Berkeley — have found that the search for information accesses the same neural code as the search for money. Their findings appear in the journal PNAS.

"To the brain, information is its own reward, above and beyond whether it's useful," says co-author and associate professor Ming Hsu, Ph.D.

"And just as our brains like empty calories from junk food, they can overvalue information that makes us feel good but may not be useful — what some may call idle curiosity."

Ming Hsu, Ph.D.

Seeking information for information's sake

According to Hsu: "Our study tried to answer two questions. First, can we reconcile the economic and psychological views of curiosity, or, why do people seek information? Second, what does curiosity look like inside the brain?"

For this purpose, the researchers started by administering functional MRI (fMRI) scans as volunteers played a gambling game. In this game, participants had to assess a series of lotteries and then make a choice, deciding how much money they wanted to invest in order to uncover more information about winning odds.

Some lotteries featured more valuable information, while others held very little information. The participants mostly made logical choices, considering the economic value of the information in each lottery — with value referring to how much money the given information could help them win in the game.

However, there was a catch. When there were higher stakes, people's curiosity about information increased, even when that information was unhelpful in making gameplay decisions.

Based on this observation, the researchers thought that the players' behavior was likely explained by a conflation of economic motivation and psychological (curiosity-driven) impulses.

Thus, they suspected that people seek information not just because it has value and can bring them benefits but also because we simply want to know, regardless of whether we intend to use the information or whether it is useful at all. At the core of this is the thrill of anticipation, the two authors note.

"Anticipation serves to amplify how good or bad something seems, and the anticipation of a more pleasurable reward makes the information appear even more valuable," Hsu explains.

Information overload is 'just like junk food'

When the researchers went on to analyze the fMRI scans, they saw that accessing information during the gambling game activated the striatum and the ventromedial prefrontal cortex — two regions involved in the brain's reward circuit.

These areas also respond to money, food, and recreational drugs, and they produce dopamine, a hormone and chemical messenger that plays a key role in directing motivation.

The researchers also found that the brain appeared to use the same kind of neural "code" when responding to amounts of money and information about winning odds in the game.

"We were able to demonstrate for the first time the existence of a common neural code for information and money, which opens the door to a number of exciting questions about how people consume, and sometimes overconsume, information," says Hsu.

The fact that there is a common code for monetary value and information and that it activates brain regions involved in the reward cycle could mean that people might actually get addicted to information.

This could have implications as to why we overconsume information, such as when we are unable to stop checking notifications on our phones.

"The way our brains respond to the anticipation of a pleasurable reward is an important reason why people are susceptible to clickbait," notes Hsu.

While, throughout the past, the human race hungrily sought information to maximize the odds of survival, easy access to useless information may now lead to an overload.

"Just like junk food, this might be a situation where previously adaptive mechanisms get exploited now that we have unprecedented access to novel curiosities," Hsu warns.

Source: Medical News Today

How long will a person with stage 4 colon cancer live?

Stage 4 colon cancer occurs when cancer in the colon spreads, or metastasizes, to other tissues and organs. Colon cancer most often spreads to the liver, but it may also reach the lungs, the lymph nodes, or the lining of the abdominal cavity.

The American Cancer Society (ACS) note that the 5-year relative survival rate for people with stage 4 colon cancer that has spread is 14%.

However, everyone is different, and other factors contribute to a person's survival rate.

Diagnosis

The correct diagnosis of colon cancer may take patience, as doctors use many tests to detect and locate cancer.

If they identify cancer, they will also use more tests to see whether it has spread.

The tests and processes that can aid a colon cancer diagnosis include:

a physical examination

blood tests

a colonoscopy to look inside the rectum

a biopsy, in which the doctor takes a sample of tissue and sends it to a laboratory for analysis

molecular testing to help identify specific characteristics of the tumor that may be important for treatment

imaging tests, such as CT, PET, ultrasound, or MRI scans, to see whether cancer has spread

a chest X-ray to check whether cancer has spread to the lungs

After running all of the necessary tests, a doctor will discuss the diagnosis with the individual.

Decisions

Anyone who receives a stage 4 colon cancer diagnosis will have to make some decisions about the way forward, particularly regarding treatment options.

It is important to discuss all of the options with a doctor and to understand the goal of each treatment.

Treatment options

The treatment options available to people with stage 4 colon cancer are more limited than those suitable for the earlier stages of this cancer. However, there are still some treatment options to consider, as well as other factors to keep in mind.

Surgery

When cancerous cells have spread to distant organs and tissues, surgery is unlikely to cure cancer. There are some cases in which surgery may still be a good option, though.

If a scan reveals that the cancer has only spread to a few small areas, surgery may still be possible. By surgically removing the cancerous cells, doctors hope to help the person live longer.

These surgeries will involve the removal of part of the colon as well as the nearby lymph nodes. Additional surgery may remove the areas of tissue into which the cancer has spread. Doctors will typically also recommend chemotherapy, either before or after the surgery.

If the tumor cells are too large to remove, or there are too many of them, doctors will recommend chemotherapy before the person undergoes any surgical procedures. If this shrinks the tumors, they may then ask a surgeon to proceed with the surgery.

Doctors may also need to perform additional surgical procedures if the cancerous growth is likely to obstruct the colon or is already blocking it. In some cases, minimally invasive surgery, such as placing a stent, may be possible. Surgeons can place a stent, which is a hollow tube that typically consists of mesh metal or plastic, into the colon during a colonoscopy. When successful, a stent may help keep the colon open and make more invasive surgery unnecessary.

Doctors may also recommend a diverting colostomy, which essentially cuts the colon above the cancerous tissue and diverts the waste from the body out through a small opening in the skin.

Chemotherapy

If the colon cancer has spread too far for surgery to be effective, chemotherapy is the primary treatment option.

Most people with stage 4 colon cancer will receive chemotherapy or specific targeted therapies to help control the cancer progression or symptoms.

Doctors may recommend some treatment regimens that include a targeting drug, which targets either the vascular endothelial growth factor (VEGF) pathway or the epithelial growth factor receptor (EGFR) pathway.

The choice between regimens will vary in each situation. The most suitable option will depend on the types of treatment that a person has had before, their overall health, and their responsiveness to treatment.

It is not uncommon for doctors to try multiple treatments. If the cancer does not respond to the first treatment, they may stop that treatment and start another instead.

Radiation therapy

Doctors may also recommend radiation therapy in late-stage colon cancer to help reduce symptoms such as pain and discomfort. This treatment might even shrink the tumor for a time, but it will not usually cure the cancer.

Hepatic artery infusion

A hepatic artery infusion may be a treatment option for people with colon cancer that has spread to the liver. Hepatic artery infusion is a type of regional chemotherapy, which involves delivering a chemotherapy drug directly into the hepatic artery in the liver. This treatment may help destroy cancer cells without harming the healthy liver cells in the process.

Ablation or embolization

Ablation or embolization may be appropriate for people who have metastatic or reoccurring colorectal cancer that causes a few tumors in the lung or liver that are less than 4 centimeters across.

Ablation uses either radio frequencies, microwaves, or alcohol — which people also call percutaneous ethanol injection (PEI) — to target and kill cancer cells while leaving the surrounding tissues relatively unharmed.

During embolization, a doctor will inject substances into the blood vessels to try to block or reduce the blood flow to cancer cells in the liver.

Palliative care

If cancer progresses to many distant organs and tissues, surgery may not help extend a person's lifespan. Other treatment options can cause discomfort and may produce additional symptoms that make the person's quality of life worse.

In these cases, people may decide against medical treatment that seeks to cure the cancer and instead opt for palliative care to try to make living more comfortable.

Palliative care will typically involve finding ways to manage pain and reduce a person's symptoms so that they can live comfortably for as long as possible.

Source : Medical News Today

What are mitochondria?

Mitochondria are often referred to as the powerhouses of the cell. They help turn the energy we take from food into energy that the cell can use. But, there is more to mitochondria than energy production.

Present in nearly all types of human cell, mitochondria are vital to our survival. They generate the majority of our adenosine triphosphate (ATP), the energy currency of the cell.

Mitochondria are also involved in other tasks, such as signaling between cells and cell death, otherwise known as apoptosis.

In this article, we will look at how mitochondria work, what they look like, and explain what happens when they stop doing their job correctly.

The structure of mitochondria

Mitochondria are small, often between 0.75 and 3 micrometers and are not visible under the microscope unless they are stained.

Unlike other organelles (miniature organs within the cell), they have two membranes, an outer one and an inner one. Each membrane has different functions.

Mitochondria are split into different compartments or regions, each of which carries out distinct roles.

Some of the major regions include the:

Outer membrane: Small molecules can pass freely through the outer membrane. This outer portion includes proteins called porins, which form channels that allow proteins to cross. The outer membrane also hosts a number of enzymes with a wide variety of functions.

Intermembrane space: This is the area between the inner and outer membranes.

Inner membrane: This membrane holds proteins that have several roles. Because there are no porins in the inner membrane, it is impermeable to most molecules. Molecules can only cross the inner membrane in special membrane transporters. The inner membrane is where most ATP is created.

Cristae: These are the folds of the inner membrane. They increase the surface area of the membrane, therefore increasing the space available for chemical reactions.

Matrix: This is the space within the inner membrane. Containing hundreds of enzymes, it is important in the production of ATP. Mitochondrial DNA is housed here (see below).

Different cell types have different numbers of mitochondria. For instance, mature red blood cells have none at all, whereas liver cells can have more than 2,000. Cells with a high demand for energy tend to have greater numbers of mitochondria. Around 40 percent of the cytoplasm in heart muscle cells is taken up by mitochondria.

Although mitochondria are often drawn as oval-shaped organelles, they are constantly dividing (fission) and bonding together (fusion). So, in reality, these organelles are linked together in ever-changing networks.

Also, in sperm cells, the mitochondria are spiraled in the midpiece and provide energy for tail motion.

Mitochondrial DNA

Although most of our DNA is kept in the nucleus of each cell, mitochondria have their own set of DNA. Interestingly, mitochondrial DNA (mtDNA) is more similar to bacterial DNA.

The mtDNA holds the instructions for a number of proteins and other cellular support equipment across 37 genes.

The human genome stored in the nuclei of our cells contains around 3.3 billion base pairs, whereas mtDNA consists of less than 17,000.

During reproduction, half of a child's DNA comes from their father and half from their mother. However, the child always receives their mtDNA from their mother. Because of this, mtDNA has proven very useful for tracing genetic lines.

For instance, mtDNA analyses have concluded that humans may have originated in Africa relatively recently, around 200,000 years ago, descended from a common ancestor, known as mitochondrial Eve.

What do mitochondria do?

Although the best-known role of mitochondria is energy production, they carry out other important tasks as well.

In fact, only about 3 percent of the genes needed to make a mitochondrion go into its energy production equipment. The vast majority are involved in other jobs that are specific to the cell type where they are found.

Below, we cover a few of the roles of the mitochondria:

Producing energy

ATP, a complex organic chemical found in all forms of life, is often referred to as the molecular unit of currency because it powers metabolic processes. Most ATP is produced in mitochondria through a series of reactions, known as the citric acid cycle or the Krebs cycle.

Energy production mostly takes place on the folds or cristae of the inner membrane.

Mitochondria convert chemical energy from the food we eat into an energy form that the cell can use. This process is called oxidative phosphorylation.

The Krebs cycle produces a chemical called NADH. NADH is used by enzymes embedded in the cristae to produce ATP. In molecules of ATP, energy is stored in the form of chemical bonds. When these chemical bonds are broken, the energy can be used.

Cell death

Cell death, also called apoptosis, is an essential part of life. As cells become old or broken, they are cleared away and destroyed. Mitochondria help decide which cells are destroyed.

Mitochondria release cytochrome C, which activates caspase, one of the chief enzymes involved in destroying cells during apoptosis.

Because certain diseases, such as cancer, involve a breakdown in normal apoptosis, mitochondria are thought to play a role in the disease.

 Source: Medical News Today