New therapy for brain degeneration

New therapy for brain degeneration (The Hindu: 20170810)

http://www.thehindu.com/sci-tech/health/new-therapy-for-brain-

degeneration/article19459049.ece

A staff member holds a human brain in a brain bank in the Bronx borough of New York City

on June 28, 2017. | Photo Credit: REUTERS

A single injection of a fragment of a life-extending protein hormone could improve cognition

in those with neurodegenerative illnesses, according to new research.

The klotho protein was found to enhance cognitive and physical performance in ageing or

impaired mice, said a study carried out by scientists at the University of California, San

Francisco and published in the journal Cell Reports.

“Treatment with a klotho fragment enhances brain function across the lifespan and could

represent a new therapeutic strategy to boost brain resilience,” said lead author Dena Dubal.

Morality police

Rage of the morality police (The Hindu: 20170810)

http://www.thehindu.com/opinion/op-ed/rage-of-the-morality-police/article19459152.ece

DAILY NEWS BULLETINLEADING HEALTH, POPULATION AND FAMILY WELFARE STORIES OF THE DayThursday 20170810

For writers who ‘offend’ the faceless mob, it is always a lonely battle

Let’s face it, we have always been a little intolerant of the “other”. Anyone who doesn’t

conform to what we think is the “right” way to eat/look/think is guaranteed a difficult time.

So it is that a painter is forced to live and die in exile; a writer has to declare himself “dead”

in literary terms before a court grants him a fresh lease of life; cricket pitches are dug up to

keep a team out; a face smeared with tar for daring to speak up and so forth.

The explicit reality

When Jharkhand writer Hansda Sowvendra Shekhar finds himself being pilloried by people

who may not have actually read what he has written, he is not alone, but it will be a lonely

battle. To those saying he has slighted Adivasi culture in a story included in a collection of

erotic stories, they must turn to his fiction tuned to reality. One of the most powerful stories

in his The Adivasi Will Not Dance (2015) is the eponymously titled one, the last in the

collection. A group of Santhal dancers with their “tamak and tumdak” are gathered to

perform for the visiting President of India. When the troupe master Mangal Murmu refuses,

he is harassed, gagged and feels “helpless and so foolish”. All he wanted to do was protest

against his people being used as “toys”. As Murmu rages: “Someone presses our ‘ON’

button... and we Santhals start beating rhythms on our tamak... while someone snatches away

our dancing grounds. Tell me, am I wrong?”

Today, Shekhar, who won the Sahitya Akademi Yuva Purashkar in 2015 for The Mysterious

Ailment of Rupi Baskey, must be feeling a little “helpless and foolish” for the manner in

which self-appointed Adivasi groups have lashed out against him for “objectifying Santhal

women”, his writing branded as pure “porn”. Yes, he writes about sex, explicitly, but it’s a

distressing read — about girls selling their bodies, for ₹50 and two bread pakoras (November

is the Month of Migrations), for instance. Then again, isn’t that a reflection of reality? Just

turn to the newspapers; haven’t we read about girls from Jharkhand being rescued from the

brothel or from a house where they had been abused?

In 2015, award-winning Tamil writer Perumal Murugan declared himself literary “dead” after

conservative caste groups harassed him and sought a ban against his novel Maadhorubaagan

(One Part Woman), written in 2010, saying it was prurient. A year later, the Madras High

Court rejected the demand for banning the book, advising those who were hurt by it to stay

away from it. Murugan’s One Part Woman is about a couple’s efforts to conceive a child and

the taunts they face from the community; and why they pin their hopes on an age-old temple

festival when rules on sex are relaxed for one night. In his Treatise on Tolerance, French

philosopher Voltaire argued that while “tolerance has never provoked a civil war; intolerance

has covered the Earth in carnage.” We are unfortunately seeing a lot of it around us.

Abortion

Woman gets SC nod to abort 26-wk-old fetus (The Times of India:

20170810)

http://epaperbeta.timesofindia.com/Article.aspx?eid=31808&articlexml=Woman-gets-SC-

nod-to-abort-26-wk-10082017016016

The Supreme Court allowed a woman to terminate her pregnancy on Wednesday , relying on

a medical report that the 26week-old fetus was without a skull and would not be able to

survive.

The medical board report suggested if the pregnancy was allowed to run its full course, it

could pose severe mental injury to the 26-year-old woman.

The medical board of Mumbai-based Sir JJ Hospital, where the woman was examined, said

that she wanted to terminate the pregnancy as the fetus was not likely to survive and it was

causing immense mental agony to her.

“We consider it appropriate in the interest of justice and particularly , to permit the petitioner

(woman) to undergo medical termination of her pregnancy under the provisions of Medical

Termination of Pregnancy Act, 1971,“ a bench comprising Justice S A Bobde and Justice L

Nageswara Rao said.

“The condition of the fetus is not compatible with life. The medical evidence clearly suggests

that there is no point in allowing the pregnancy to run its full course since the fetus would not

be able to survive outside the uterus without a skull,“ the bench noted in its order.

The court was also informed that the woman understood that her fetus was abnormal and the

risk of mortality was high. It directed that the termination of pregnancy would be performed

by the doctors of the hospital where she underwent the medical check-up.

The woman had moved the court for permission to terminate her pregnancy .Section 3(2)(b)

of the Medical Termination of Pregnancy (MTP) Act prohibits abortion of a foetus after 20

weeks of pregnancy.

Mental health

Mental health is not a priority at this University (Hindustan Times:

20170810)

http://www.westerngazette.ca/opinion/mental-health-is-not-a-priority-at-this-

university/article_6be31f02-665a-11e6-a09d-5345a82b1872.html

I have been on the Dean’s Honor List, worked tirelessly on my faculty council and

volunteered countless hours to the Orientation program, yet I am known to certain members

of the administration as the girl who was in the psych ward.

My journey accessing Western’s mental health resources (or lack thereof) began in

November 2014 when I was booked an appointment within 24 hours of revealing my suicidal

ideations. I was shocked how quickly I was able to get an appointment but then again, in my

experience, the mere mention of the word “suicidal” quickly grabs the attention of an

institution that seem to be more concerned with liability over safety of its students.

Nevertheless, after a psychiatric assessment, I was placed on medication, reassessed two

weeks later and then no longer received follow up. I fell through the cracks of an

underfunded system and failed to receive counselling as I was promised by my psychiatrist.

My condition deteriorated as I failed to keep up in school, withdrew from my social life and

lost pleasure in activities that used to bring me joy. This experience was in no way unique —

it is likely the experience of many, though perhaps my interactions with university

administration is rather distinctive.

Due to a variety of factors, my condition worsened in my third year at Western. After several

suicide attempts, I was admitted to Victoria Hospital. Academically, everything was put on

hold. Where things got complicated was in terms of my co-curriculars. I was still interested in

maintaining the same commitments as I had in the past, but some university administration

and student leaders disagreed with me.

I would like to preface this by saying that as a cisgendered white woman, I despise even

labelling my experience as discrimination, but with great hesitation I admit that by definition

I have fallen victim to the prejudice of narrow-minded individuals. With no hesitation I

believe that my mental illness was used as a factor in a hiring decision for a volunteer

position. I was promised that my “standing as an applicant [would] not be compromised in

any way” when receiving accommodation.

My “motivations for returning” to this position were brought into question, and I was being

asked to sit down one-on-one with one of the student leaders (which is not standard practice).

My honesty was used as a weapon against me when I chose to disclose the details of my

hospital stay. Deliberations that were supposed to be supervised were tainted by the

discussion of my mental health. None of these individuals have the qualifications or

experience to assess me or make fundamental decisions based on very limited information:

they are not experts.

I was mistaken that when applying to a program that prides itself on acceptance, respect and

mental wellness, my qualifications and experience would be taken seriously. Regardless, I am

the only individual to my knowledge who was rejected post-interview as a returning member.

My weeks at the hospital were not a result of any university student or administrator, but my

mental state was further affected by the difficulty of the process and the way I was treated by

individuals involved.

I fought tirelessly to reverse the decision made by individuals who were so quick to judge my

ability to perform. There were countless emails exchanged between myself and relevant

university employees. When I questioned inconsistent information during a phone call, I was

received with a shocking tone that practically questioned my sanity. I wasn’t treated with any

compassion. There was even a scheduled face-to-face meeting with a university employee.

When I cancelled this meeting the night before due to an unbearable amount of anxiety,

another university employee proceeded to call my parents in order to “make sure I was okay.”

Why didn’t they call me, you ask?

I believe they were interested in assessing whether I was alive or not, to see if they had

another suicide on their hands: they weren’t so much concerned for my safety but whether or

not they had a liability brewing. As a result, my confidentiality was breached as I had never

given permission for my parents to be called.

To this day, three months after I had been discharged from the hospital, there still seems to be

gossiping of my stay. When I had introduced myself to a university employee who I had

never spoken with, they asked me “Wait, Anastasia? The one in the hospital?”

Some students complain about how they’re only defined as their student number. Imagine

being defined by your time of weakness, rather than your courage by taking charge of your

mental illness. I’m not ashamed of having been a psychiatric patient for seven weeks. I’m

ashamed that the individuals involved are planning an event around mental health for first-

year students this September. Further, I’m ashamed of calling myself a student at a university

that boasts about their efforts to end the stigma.

Sleep

How sleep helps us to remember and forget at the same time (Medical

News Today: 20170810)

http://www.medicalnewstoday.com/articles/318887.php

Can we both learn and unlearn while we sleep? A new study suggests that we can. Both

processes occur during different phases of sleep, the research shows.

Our brains have the ability to come up with creative solutions to problems when we least

think about them, and, some think, to learn new things while we are resting.

Most of the wonderful work that our brains do is invisible, and what goes on under the hood

has preoccupied neuroscientists for at least the past two centuries.

It is a known fact that sleep and memory are deeply connected. For instance, studies have

shown that neuroplasticity - that is, the brain's ability to retrace new connections between

neurons and to forge new pathways that enable us to learn new information - is heavily

dependent on sleep. It is during sleep that our synapses relax and regain their plasticity.

Despite some of these studies suggesting that our brains have the ability to learn while asleep,

the scientific literature available shows mixed results. Some studies managed to produce

evidence in favor of this theory, while others did not.

This is why a team of scientists based in Paris, France, set out to examine in more depth

whether or not learning occurs during sleep. They hypothesized that perhaps the reason why

different studies produced different results is that they studied different sleep phases, each

with a different effect on learning abilities.

The researchers - from the École Normale Supérieure (ENS) and the Paris Descartes

University - were led by Thomas Andrillon, Ph.D., of the Département d'Études Cognitives at

ENS, and the findings were published in the journal Nature Communications.

Studying different sleep phases

To test their hypothesis, Dr. Andrillon and team played sequences of sound to 28 participants

while they were asleep. During sleep, their brain activity was monitored with the help of an

electroencephalogram (EEG), which records the brain's electrical activity.

Using the readings from the EEG, Dr. Andrillon and colleagues looked at three sleep phases:

rapid eye movement (REM) sleep; light non-REM (NREM) sleep; and deep NREM sleep.

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REM sleep accounts for around 25 percent of any sleep cycle, tending to occur between 70

and 90 minutes after a person falls asleep. Likewise, NREM sleep also has several substages.

Because of the different brain waves associated with these different sleep phases, an EEG can

detect when a person is going through a specific sleep phase.

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Additionally, an EEG can also decide whether the brain is responding to new auditory

information or to information that has already been learned.

The researchers examined EEG data. They also asked participants, upon waking, to recognize

the sounds that they were played while asleep, and the team measured their learning

performance in a series of tests.

Finally, the participants were repeatedly played some of the same sound sequences, in an

attempt to see how easily they relearned information that had previously been presented to

them.

Some phases help learning, others inhibit it

Overall, the study revealed significant differences between the sleep phases. When

participants heard the sound sequences during REM sleep or during light NREM sleep, they

were better able to recognize the sounds. By contrast, when they were exposed to the new

sounds during deep NREM sleep, they performed significantly worse at the recognizing tests

when awake.

These findings were confirmed by EEG markers. And quite surprisingly, the experiments

revealed that during deep NREM sleep, the brain seems to not aid learning as well as

suppress it.

After waking, not only did the participants find it difficult to recognize the sounds that were

played to them while asleep, but they also found it even harder to (re)learn them than entirely

new sounds. The role of deep NREM sleep, therefore, seems to be to suppress previous

learning.

Speaking to Medical News Today about the findings, the study's lead investigator said:

"[The] biggest surprise came from brain's ability to unlearn. Thus, it seems that during sleep,

we can either form new memories, learn, or do the reverse: suppress memories and unlearn."

The findings are significant because they help to harmonize two previously discordant

theories. One theory referenced by the authors in the study suggests that sleep's main function

in memory is to consolidate newly acquired information. The other theory sees sleep as a way

to discard useless information that would otherwise back up and overwhelm our brains'

capacities.

When asked about the possible mechanisms that could explain the findings, Dr. Andrillon

pointed to the neuromodulator acetylcholine as a potential key player.

"Interestingly, the memories formed during light NREM sleep were erased as sleepers

transitioned toward deep NREM sleep. We interpret this reversal as the effect in brain

chemistry during sleep," he told MNT.

"Indeed, sleep is characterized by large changes in the concentration of neuromodulators," he

continued. "Acetylcholine in particular is high during both wakefulness and REM sleep but is

low during deep NREM sleep."

"Crucially, acetylcholine can modulate synaptic plasticity. Under high concentration, the

activation of a given memory will lead to its strengthening (due to an increase in the strength

of synaptic contacts between neurons). Under low concentration, the reverse would occur,"

explained Dr. Andrillon.

Based on this, a possible direction for future research would "target the precise mechanisms

of learning and unlearning during sleep [focusing on] a model in which the neuromodulator

acetylcholine plays a central role in determining brain's ability to learn or unlearn."

Vitamin B-3

Could vitamin B-3 help to prevent melanoma? (Medical News Today:

20170810)

http://www.medicalnewstoday.com/articles/318876.php

In a new review, researchers claim that nicotinamide may have the potential to prevent

melanoma - the deadliest form of skin cancer - and they say that it should be tested for this

purpose in clinical trials.

Nicotinamide, also referred to as niacinamide, is a form of vitamin B-3, or niacin. It is present

in a variety of foods, including milk, eggs, fish, green vegetables, and lean meats. It is also

available as a dietary supplement.

Nicotinamide is already recognized as an effective cholesterol-lowering medication, and it is

also used for the prevention and treatment of pellagra, which is a disease caused by niacin

deficiency.

The new review - conducted by Dr. Gary Halliday, of the University of Sydney in Australia,

and colleagues - suggests that nicotinamide could also help to prevent melanoma, particularly

in people who are at high risk of the disease.

Dr. Halliday and his team recently reported their findings in the journal Photodermatology,

Photoimmunology & Photomedicine.

Melanoma is a form of skin cancer that begins in melanocytes. These are skin cells that

produce a pigment called melanin, which works to protect the deeper skin layers against the

harmful effects of ultraviolet (UV) radiation.

According to the American Cancer Society, there will be 87,110 new cases of melanoma

diagnosed in the United States this year, and around 9,730 people will die from the disease.

Exposure to UV radiation is considered a key risk factor for melanoma; it damages the DNA

in skin cells. This DNA damage can cause the skin cells to grow out of control, which may

lead to cancer.

Nicotinamide boosts skin DNA repair

While sunscreen is widely recommended for skin cancer prevention, Dr. Halliday and team

say that the benefits of sunscreen for melanoma prevention are "inconclusive."

"These conflicting results may stem from insufficient application [...] and reapplication of

sunscreen and increased motivation to sunbathe, as long as sunscreen is applied," write the

authors.

However, the researchers say that there are a number of other agents that have shown promise

for melanoma prevention - one of which is nicotinamide.

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For their research, Dr. Halliday and colleagues reviewed numerous studies that have

previously investigated the effects of nicotinamide against melanoma cancer cells. The results

suggest that the vitamin may be an effective candidate for prevention, especially for patients

at high risk of melanoma.

The team cites a wealth of research that reveals how nicotinamide can protect the skin against

the harmful effects of UV radiation. For example, studies in human cell lines have shown that

nicotinamide can boost DNA repair in response to UV exposure.

Research has also indicated that the vitamin might reduce immunosuppression and

inflammation, both of which are known to contribute to cancer development. The team

therefore hypothesizes that nicotinamide could reduce the risk of melanoma.

Clinical trials warranted

In their review, Dr. Halliday and colleagues discuss the results of The Oral Nicotinamide To

Reduce Actinic Cancer study, which was a phase III clinical trial of nicotinamide for the

prevention of non-melanoma skin cancers (NMSCs).

The trial involved 386 participants, each of whom had been diagnosed with at least two non-

melanoma skin cancers within the past 5 years.

Participants were randomized to one of two groups: one group took 500 milligrams of

nicotinamide daily for 12 months, while the other group received a placebo.

Over the 12-month period, the development of new non-melanoma skin cancers was found to

be 23 percent lower for subjects who took nicotinamide, compared with those who took a

placebo.

While this trial was unable to investigate the effects of nicotinamide against melanoma - due

to few cases of the disease among participants - Dr. Halliday and team say that the results

suggest that it is worth conducting clinical trials to assess how the vitamin may fare against

this deadly skin cancer.

"To assess melanoma incidence, the cohort would need to recruit individuals at high

melanoma risk, such as those with a previous melanoma, [or] those with a genetic

susceptibility to develop melanomas," the authors note.

"The study was also conducted over a 12-month period," they add, "and it is likely that a

longer trial period, and a much larger study cohort, is necessary to adequately assess the

incidence of melanomas, which are much less frequent than NMSCs."

In conclusion to their review, Dr. Halliday and team say:

"Based on current clinical evidence of the use of NAM [nicotinamide] in NMSC and early in

vitro studies conducted with melanocytes and melanoma cells, randomized placebo-

controlled trials are now warranted to determine the efficacy and safety of NAM for

melanoma prevention in high-risk patients."

Hyperpyrexia

Hyperpyrexia: Causes, symptoms, and treatment (Medical News Today:

20170810)

http://www.medicalnewstoday.com/articles/318856.php

Hyperpyrexia is another term for a very high fever. The medical criterion for hyperpyrexia is

when someone is running a body temperature of more than 106.7°F or 41.5°C.

Some doctors lower the measure for hyperpyrexia to include anyone with a body temperature

of 106.1°F or 41.1°C and above.

Fevers, including very high fevers, are never illnesses in themselves, or the causes of

illnesses. Instead, they are symptoms of other problems, such as an infection or injury. Viral

or bacterial infections cause most fevers. However, in hyperpyrexia, that is not always the

case.

Hyperpyrexia is an emergency that needs immediate attention from a medical professional.

Contents of this article:

What is hyperpyrexia?

Causes of hyperpyrexia

What are the symptoms?

Treatment and management

How is hyperpyrexia diagnosed?

Outlook

Fast facts on hyperpyrexia:

Viruses that can cause hyperpyrexia include enterovirus infection, roseola, rubeola, and

malaria.

Hyperpyrexia is associated with a body temperature of more than 106.7°F or 41.5°C.

Typically, treatment for hyperpyrexia focusses on the underlying disease, if one exists.

The outlook for hyperpyrexia depends on the underlying condition causing the state of very

high fever.

What is hyperpyrexia?

In hyperpyrexia and most other cases of fever, the brain tells the body to raise its baseline

temperature above normal. The body responds to the brain's messages and raises its

temperature to a new baseline. This reaction normally happens as a result of an infection or

trauma.

Hyperpyrexia differs from hyperthermia, a medical term for the uncontrolled rise in body

temperature due to excess amounts of body heat generated.

In hyperthermia, the brain is not regulating the rise in temperature the way it does with other

fevers. Rather, the body cannot handle the heat from environmental causes, and so it

overheats.

Cases of heat stroke are due to hyperthermia, and not to hyperpyrexia.

Causes of hyperpyrexia

Usually, instances of hyperpyrexia are associated with viral or bacterial infections. Some

other causes include the following:

Intracranial hemorrhage

In some cases, bleeding in the brain known as intracranial hemorrhage causes hyperpyrexia.

Accidents or other traumas and strokes are the most likely cause of intracranial hemorrhage.

The bleeding in the brain can affect an area of the brain called the hypothalamus, which is

responsible for regulating the body's temperature.

Sepsis

In rare cases, hyperpyrexia may result from sepsis. Sepsis is a potentially life-threatening

response to an infection caused by the immune system. The overwhelming immune system

response gets into the blood, which may cause organ damage or failure.

Anesthesia

People may experience hyperpyrexia due to a direct side effect of general anesthesia,

occurring when there is an underlying disease of muscle. In these cases, a person's

temperature rises rapidly while under anesthesia, requiring doctors to make adjustments to

lower the body's temperature again.

Hyperpyrexia in children

Kawasaki syndrome or disease is a potential cause of hyperpyrexia, especially in children.

Kawasaki syndrome causes inflammation to the medium-sized arteries throughout the body.

One sign of Kawasaki disease is high fever, which can result in hyperpyrexia if left untreated.

What are the symptoms?

Headache pyrexia

Headaches can be a sign that a fever is becoming more severe.

Symptoms of hyperpyrexia vary from person to person, depending on how long the condition

lasts and if it worsens. Early symptoms may include:

increased thirst

extreme sweating

dizziness

muscle cramps

fatigue and weakness

nausea

light-headedness

As the high temperature persists or gets worse, the severity of the symptoms can increase.

This situation can lead to:

headache

contracted pupils

mild confusion

pale, moist, and cool skin

vomiting or upset stomach

decreased urination or inability to urinate

In prolonged periods of a temperature of more than 106.1°F, the following symptoms may

occur:

extreme confusion

loss of consciousness

rapid, shallow breathing

dry, hot, and red skin

weak, fast pulse

widened pupils

seizures

It is essential to seek treatment for fevers over 106.1°F to help prevent serious long-term

complications or death.

Treatment and management

As hyperpyrexia is caused by another disease, treating the latter will usually cause the body's

temperature to go down.

When the body temperature starts reaching 106.1°F and higher, it may be necessary to treat

the fever itself, as well as the underlying cause. Direct treatment of hyperpyrexia may

include:

a cool bath or cold, wet sponges put on the skin

liquid hydration through IV or from drinking

fever-reducing medications, such as dantrolene

In cases of malignant hyperpyrexia caused from general anesthesia, doctors will need to take

steps to reduce the patient's fever.

How is hyperpyrexia diagnosed?

Thermometer hyperpyrexia

A thermometer is used to diagnose hyperpyrexia.

Diagnosing hyperpyrexia is done using a thermometer. If the reading is over 106.1°F, then

the person has the symptoms of hyperpyrexia.

Since hyperpyrexia itself is not a diagnosis and only a symptom of a larger problem, finding

the underlying cause of the high fever is more important and often more challenging.

A doctor will assess the person's physical state and run tests to rule out the more common

causes of high fever. These test may include the following:

blood work, to check for signs of infection

image studies of the brain to check for intracranial hemorrhage

Further tests will largely depend on any other symptoms the person has.

Outlook

If the fever is not treated and a person's temperature brought down to a safe level,

hyperpyrexia can cause permanent brain damage or death.

However, in most circumstances, correct treatments can lower the fever safely, giving doctors

time to diagnose and treat the underlying cause of the hyperpyrexia.

Alzheimer's disease

Alzheimer's disease: Targeting enzyme may reverse memory loss

After many years of research, scientists have found that by blocking one specific enzyme,

Alzheimer's-related memory loss could be reversed or prevented.

A new study has suggested that it may be possible to reverse the memory loss that occurs in

Alzheimer's disease with drugs that selectively block the ability of the HDAC2 enzyme to

interfere with the communication between brain cells.

Previous attempts to target HDAC2 have not been satisfactory because the drugs that were

used also disrupted other functions of the enzyme, producing toxic side effects.

Now, research has shown that blocking a molecule called sp3 that binds to HDAC2 might be

a way to stop them both from disrupting synaptic function, or the communication between

brain cells that is important for memory.

A report on the study, led by researchers from the Massachusetts Institute of Technology

(MIT) in Cambridge, is published in the journal Cell Reports.

Senior author Prof. Li-Huei Tsai, director of the Picower Institute for Learning and Memory

at MIT, says that they believe that HDAC2 is a master regulator of genes that control

memory and that because its levels are raised in Alzheimer's disease, it blocks the expression

of those genes.

"If we can remove the blockade by inhibiting HDAC2 activity or reducing HDAC2 levels,"

Prof. Tsai explains, "then we can remove the blockade and restore expression of all these

genes necessary for learning and memory."

Growing number of people with Alzheimer's

Alzheimer's disease is the most common form of dementia, a progressive brain-wasting

condition that gradually diminishes people's ability to think, remember, reason, and make

decisions.

As the symptoms worsen, people lose the ability to hold a conversation and respond to what

is happening around them.

Experts do not yet know exactly what causes Alzheimer's disease, but they say that it could

be due to several factors that arise differently in different people.

Although it can affect younger people, Alzheimer's disease is more common among adults

aged 60 and older.

Around 5 million people are thought to be living with Alzheimer's disease in the United

States, and this number is expected to rise to 14 million by 2050.

Synaptic plasticity

The new study concerns the disruption of a biological process called synaptic plasticity,

which is thought to be important for learning and memory.

Research on what happens at synapses - which are the junctions between brain cells - has

revealed that they are "plastic" and not fixed as the soldered joints in electronic circuits are.

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Synaptic plasticity is defined as a biological process whereby synapses change over time,

depending on specific patterns of activity.

The synaptic changes affect various properties, including the strength of communication

between brain cells, which impacts memory.

Prof. Tsai has been researching the role that enzymes called HDACs play in memory loss for

over a decade. In 2007, she discovered that blocking HDAC activity in mice could reverse

memory loss. There are around a dozen types of HDAC in humans.

HDAC2 blocks memory-related genes

HDACs affect memory by altering histones, which are the proteins that help to package DNA

into a structure called chromatin. The effect of HDAC is to condense chromatin, which, in

turn, reduces the expression of some genes in the DNA.

In later research, Prof. Tsai found that a particular HDAC in humans called HDAC2 blocked

some genes that are important for memory, and that levels of the enzyme are higher in people

with Alzheimer's and also in mouse models of the disease.

Compounds that inhibit HDAC2 have already been tested, but most of these have undesirable

side effects. For example, they interfere with HDAC1, which is important for cell

proliferation, especially in white and red blood cells.

Therefore, Prof. Tsai and colleagues set out to find a way to target only the activity of

HDAC2 that interferes with memory by searching for proteins that help the enzyme to bind to

the relevant genes.

Gene expression data from post-mortems of people who did not have Alzheimer's disease -

some whose brains had high and some whose had low levels of HDAC2 - helped the team to

find more than 2,000 genes that might be involved with HDAC2 activity.

Sp3 helps HDAC2 to block memory genes

Using other information that they already had about how the genes behave with HDAC2, the

team whittled down the candidates to three.

Further tests on these three led them to Sp3, a "transcription factor" molecule that helps

HDAC2 to alter chromatin and block the memory genes on the DNA.

Gene expression data from post-mortem samples taken from brains of people who died with

Alzheimer's disease revealed a strong link between levels of HDAC2 and Sp3.

The researchers then showed that reducing sp3 expression in a mouse model of Alzheimer's

disease restored the animals' ability to form long-term memories.

"Our findings indicate that targeting the HDAC2-Sp3 complex could enhance cognitive

function without affecting HDAC2 function in other processes."

The team also found a molecule that might serve as a basis for developing a drug that

prevents sp3 from binding to HDAC2 to free up the memory genes. They showed that the

molecule does not interfere with cell proliferation, as some other HDAC inhibitors do.

Prof. Tsai says that there is further work to do - such as finding a smaller version of the

molecule - before they can settle on a suitable experimental drug candidate.

She also wishes to find out how many other genes might be teaming up with HDAC2, which

could lead to other drug targets.

Alzheimer's and Parkinson's

Life-extending protein could treat Alzheimer's and Parkinson's (Medical

News Today: 20170810)

http://www.medicalnewstoday.com/articles/318861.php

New research has shown that a naturally occurring protein can improve cognition in mice

with Alzheimer's and Parkinson's disease-like characteristics. The findings open up a new

therapeutic avenue for treating these neurodegenerative illnesses.

The research was carried out by scientists at the University of California, San Francisco, and

it was led by Dr. Dena Dubal, an associate professor of neurology at the university. Their

findings were published in the journal Cell Reports.

This study builds on previous research that found that high levels of the klotho protein

correlated with improved cognition. These previous studies looked at mice that had been

genetically modified to have high levels of the protein, as well as with humans who naturally

had such elevated levels.

What the new research adds is an investigation into the potential therapeutic use of this

protein. More specifically, the new study examines whether or not the protein can be used as

a drug to quickly improve cognition in mice that have either low levels of the protein, normal

levels, or cognitive impairment.

About the relevance of the research, Dr. Dubal says, "With our new aging demographic,

cognitive dysfunction and lack of mobility are now emerging as our biggest biomedical

challenges, and there are no truly effective medical therapies for these debilitating problems."

However, her findings point to the protein hormone klotho as key for devising such therapies.

What is klotho?

Klotho is a protein that occurs naturally in the body - produced in the kidneys and the brain -

which then goes on to circulate as a hormone.

As the researchers explain in their study, klotho is known to be involved in regulating several

other key bodily processes and hormones, such as insulin and the growth of fibroblasts,

which are a type of connective tissue cell that produces collagen, among other things.

Overexpression of the protein has been shown to be life-extending in humans and a variety of

organisms, while low levels have been shown to shorten the lifespan.

With age, we lose this life-extending protein. Studies referenced by the authors of the current

research have shown that klotho levels decrease with age, with increased levels of chronic

stress, and in the presence of a neurodegenerative illness such as Alzheimer's disease or

Parkinson's.

Previous studies have also shown that natural genetic overexpression of the protein boosts

cognition and neural resilience, regardless of age. It is also known that the way it does this is

at least partially by improving the connections between the neurons' synapses through the

NMDA receptor, which is for glutamate.

But what was not known was whether or not klotho could be used therapeutically to achieve

the same effects, and if so, how quickly it can do this. For this reason, Dr. Dubal and team set

out to test its therapeutic potential.

How a klotho fragment boosts cognition

The team injected both young and aging mice (which were 18 months old - roughly the

equivalent of 65 human years) with an alpha-klotho protein fragment (αKL-F), which is

similar to the secreted hormone.

The researchers also created a mouse model wherein the rodents were genetically engineered

to have excessive levels of alpha-synuclein - that is, a protein largely responsible for

Alzheimer's and Parkinson's disease. They administered injections of αKL-F to these rodents

as well.

Dr. Dubal and team went on to test the cognitive performance of these mice by subjecting

them to a range of tests. These included the Morris water maze and the Y-maze, which assess

spatial learning and spatial memory.

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The tests revealed that young mice that had been treated with αKL-F for 4 days in a row

drastically improved their cognition, and the cognitive benefits lasted for more than 2 weeks.

As for the aging mice, these showed cognitive improvements only 2 days after receiving just

a single shot of the treatment.

Finally, receiving αKL-F treatment for a few days in a row helped to alleviate motor and

cognitive impairment in mice with neurodegenerative illness.

The study also found that for the duration of the time that αKL-F boosted cognition, the

neural signaling through the NMDA receptor was also enhanced, which, in turn, strengthened

neural connections in the hippocampus, which is a brain area key for learning and memory.

Speaking to Medical News Today about the results of the new study, Dr. Dubal said, "When

the impaired mice were treated with the hormone, they soon experienced the ability to move,

learn, and remember better - all in spite of the high levels of toxic proteins in their brains."

"The klotho treatment increased the ability of their brains to withstand and even reverse

effects of pathogenic proteins already present; it boosted their brain resilience."

Klotho may treat neurodegeneration

"The burning question in the field was, 'Does klotho have therapeutic potential?'" says Dr.

Dubal, speaking about the significance and impact of their findings. "We now know that, yes,

it does."

"Our findings suggest that treatment with a klotho fragment enhances brain function across

the lifespan and could represent a new therapeutic strategy to boost brain resilience against

neurodegenerative diseases like Alzheimer's and Parkinson's disease."

Dr. Dena Dubal

The way in which klotho improves cognition remains unclear, however. Dr. Dubal told MNT,

"Surprisingly, we did not find evidence that [αKL-F] crossed into the brain. [...] This means

that the klotho fragment probably sends a signal from the body to the brain - to increase brain

function and boost its ability to counter toxicity."

In trying to elucidate the mechanism, she draws parallels with physical exercise. "It reminds

us of the positive effects of body exercise on optimizing brain health. It also reminds us of the

beneficial effects of young blood on rejuvenating the brains of old mice."

"In both scenarios, a systemic signal or signals enhance brain functions. Could klotho

orchestrate or converge upon beneficial body-to-brain signals?"

In their future research, Dr. Dubal and her team plan to answer this question by investigating

how exactly αKL-F sends signals to the brain to improve cognition.

Swine Flu (Navbharat Times: 20170810)

http://epaper.navbharattimes.com/details/19366-25357458-1.html

Migraine (Hindustan Times: 20170810)

http://epaper.livehindustan.com/story.aspx?id=2136776&boxid=96160436&ed_date=2017-

08-10&ed_code=1&ed_page=22

Blood Cancer (Dainik Gagaran: 20170810)

http://epaper.jagran.com/ePaperArticle/10-aug-2017-edition-Delhi-City-page_24-329-4585-

4.html

Malaria ((Dainik Gagaran: 20170810)

http://epaper.jagran.com/ePaperArticle/10-aug-2017-edition-National-page_14-269-18557-

262.html