Drug Reverses Schizophrenia in Mice by Curbing Synaptic Pruning

Experimental chemical restores some lost brain cell function in schizophrenia.

Experimental chemical restores some lost brain cell function in schizophrenia.

An anticancer compound has reversed the behaviours associated with schizophrenia in mice.

On top of reversing these behaviours, the chemical also restores some lost brain cell function, the Johns Hopkins University School of Medicine research finds (Hayashi-Takagi et al., 2014).

The compound is a type of PAK inhibitor which has been tested in the treatment of cancer, Fragile X syndrome (a type of mental retardation) and Alzheimer’s disease.

Synaptic pruning

The drug works by targeting a natural process called ‘synaptic pruning’.

Synaptic pruning is one of the underlying biological processes thought to be important in the development of schizophrenia.

In adolescence it is normal for children’s brain to undergo quite extensive synaptic pruning: a process where the brain’s grey matter is lost over time.

The refining of the brain’s synapses seems to be beneficial to boosting cognitive control.

In schizophrenia, however, the pruning process gets out of control and many connections which are needed by the brain are destroyed.

The study’s leader Akira Sawa, explained the results:

“By using this compound to block excess pruning in adolescent mice, we also normalized the behavior deficit.

That we could intervene in adolescence and still make a difference in restoring brain function in these mice is intriguing.”

This is just one of many approaches being tried to tackle schizophrenia, which is a fiendishly complicated condition.

Although there is not yet evidence that the PAK inhibitor will work in humans, Sawa, the director of the Johns Hopkins Schizophrenia Center, says:

“Drugs aimed at treating a disease should be able to reverse an already existing defect as well as block future damage.

This compound has the potential to do both.”

Image credit: Birth Into Being

Copper Pinpointed as Main Environmental Cause of Alzheimer’s Disease

Two pivotal processes affected by copper may hasten the onset and progression of Alzheimer’s.

Two pivotal processes affected by copper may hasten the onset and progression of Alzheimer’s.

Copper may be one of the main environmental factors in Alzheimer’s disease, according to recent research which has identified how the metal stops the brain clearing a toxic protein.

The conclusion comes from a study of both mouse and human brain cells and is published in the journal Proceedings of the National Academy of Sciences (Singh et al., 2013).

Dr Rashid Deane of the University of Rochester Medical Center, and one of the study’s lead authors explains:

“It is clear that, over time, copper’s cumulative effect is to impair the systems by which amyloid beta [a toxic protein] is removed from the brain.

This impairment is one of the key factors that cause the protein to accumulate in the brain and form the plaques that are the hallmark of Alzheimer’s disease.”

Amyloid beta is a toxic byproduct of cellular activity which is crucial in the development of the plaques found in the brains of those with Alzheimer’s disease.

The recent study put very low levels of copper into the drinking water of mice over three months, then examined how this affected their brains.

They found that the copper accumulated in the vessels which feed blood to the brain.

The copper then disrupted the removal of amyloid beta from the brain cells.

Researchers confirmed this process in both mouse and human brain cells.

Copper penetrates the brain

In a second phase of the research, they looked at how copper affected the mice’s brain cells over time.

What they found was that with age the blood-brain barrier became ‘leaky’ so that copper could penetrate the brain.

There it tended to increase the production of amyloid beta.

Together, then, these two processes show that copper can both inhibit the clearance of amyloid beta and stimulate production in the brain.

Balanced consumption

Since copper is a ubiquitous essential metal that is vital to many bodily functions, it’s not simply a case of cutting it out of the diet.

Deane explains:

“Copper is an essential metal and it is clear that these effects are due to exposure over a long period of time. The key will be striking the right balance between too little and too much copper consumption. Right now we cannot say what the right level will be, but diet may ultimately play an important role in regulating this process.”

Image credit: ML Cohen

The Tragic Story of the Most Famous Amnesiac and Pictures of His Brain

Henry Molaison’s brain has been preserved forever as a Google Map.

Henry Molaison’s brain has been preserved forever as a Google Map.

Henry Molaison has–or rather had–the most famous amnesiac brain in psychology.

The results of tests carried out on him over the last five decades have produced thousands of academic papers examining all aspects of memory and thinking.

Molaison’s story is tragic: he agreed to experimental surgery in 1953 in an attempt to be free of very severe epilepsy which had blighted his life from an early age.

The surgery–which cut out most of his hippocampi–was successful in controlling his epilepsy, but had the unintended consequence of leaving him severely amnesic.

molaison_brain

After the surgery he lost the ability to lay down new memories, as well as losing many memories from around 1 to 2 years before the surgery was performed.

Here is conversation he had with Suzanne Corkin, a psychologist he had been working with–and seen regularly–for thirty years:

“Have we ever met before?” [Corkin asked]

“Yes, I think we have”

“Where?”

“Well, in high school?”

“Yes.”

“What school?”

“In East Hartford.”

“Have we ever met any place besides high school?”

Henry paused. “Tell you the truth, I can’t–no. I don’t think so” (from: Permanent Present Tense by Suzanne Corkin)

In fact, they didn’t meet in high school but when Corkin was a grad student. The other things Molaison ‘remembered’ were really his own pre-surgery memories. He himself had attended high school in East Hartford, Connecticut.

By carrying out experiments on Molaison’s memory, psychologists made all kinds of breakthroughs, here are a couple:

  • He  was able to learn new skills despite not remembering he had learnt them. This suggests a separation in the brain between procedural and semantic memory.
  • He could learn unconsciously when patterns were hidden in tests. This suggested that it was only certain types of new learning which he couldn’t achieve.

Molaison died in 2008 and one year later neuroscientists spent 53 hours dissecting his brain, also taking a series of detailed digital images.

These images have now been reconstructed to create a 3-D microscopic model of his brain, which exists as a Google map.

Molaison_brain2

The leader of the team, Dr. Jacopo Annese, explained:

“Our goal was to create this 3-D model so we could revisit, by virtual dissection, the original surgical procedure and support retrospective studies by providing clear anatomical verification of the original brain lesion and the pathological state of the surrounding areas of H.M.’s brain.”

Even after his death Henry Molaison continues to provide insights into how memory works; Dr Annese continues:

“For many decades, it was thought the main area of damage responsible for H.M.’s amnesia was the hippocampus. However, these new findings show that a substantial portion of H.M.’s hippocampus may have been spared by the operation. Instead, H.M.’s entorhinal cortex […] was almost completely destroyed.

This new discovery suggests that the entorhinal cortex may be more important for H.M.’s memory deficits than previously thought. Indeed, this is the same region that seems to be most heavily impacted during the earliest stages of Alzheimer’s disease.”

Henry Molaison lives on in introductory psychology courses across the world where the results of the studies carried out on him are taught to new generations of psychology students every year.

He also lives on in the form of a highly detailed Google Map of his brain.

Image credit: https://thedigitalbrainlibrary.org/

Hidden Caves in the Brain Open Up During Sleep to Wash Away Toxins

“Hidden caves” that open up in the brain may help explain sleep’s amazing restorative powers.

“Hidden caves” that open up in the brain may help explain sleep’s amazing restorative powers.

A new study published in the prestigious journal, Science, has found that the brain may wash away toxins built up over the day during sleep.

The research discovered “hidden caves” inside the brain, which open up during sleep, allowing cerebrospinal fluid (CSF) to flush out potential neurotoxins, like β-amyloid, which has been associated with Alzheimer’s disease.

To reach their discovery, researchers injected mice’s brains with a dye and monitored the flow while they were awake, asleep and anaesthetised (Xie et al., 2013).

One of the study’s authors, Dr Maiken Nedergaard, explained the results:

“We were surprised by how little flow there was into the brain when the mice were awake. It suggested that the space between brain cells changed greatly between conscious and unconscious states.”

For a long time the real physiological purpose of sleep has remained a mystery.

We know that lack of sleep causes all kinds of psychological problems like poor learning, decision-making and so on.

We also know that animals that are chronically deprived of sleep will eventually die: flies or rodents in days to weeks, humans within months or years.

Everyone who has ever enjoyed a blissfully good night’s sleep knows just how restorative it can be, but the actual physiological process wasn’t clear.

This study, though, suggests that the flushing out of toxins by the CSF may be central to sleep’s wondrous powers.

The interstitial spaces in the mouse’s brain took up only 14% of the brain’s volume while it was awake. Yet, while it slept, this increased by almost two-thirds to take up fully 23% of the brain’s total volume.

The difference might seem slight, but the actual physiological effects are profound.

During the day, the CSF mostly covers the surface of the brain. During sleep, though, the CSF is able to move deep inside.

The effect is that potential neurotoxins, like β-amyloid, are cleared twice as fast during sleep as during waking.

The results of this study–if they hold in humans–may help to explain why many neurological diseases, like strokes and dementia, are associated with problems sleeping.

It could be that lack of sleep, and restriction of the brain’s cleaning system, may cause toxic metabolites to building up, leading to long-term damage.

→ Related: 10 Sleep Deprivation Effects.

Image credit: HaoJan Chang

10 Superb Psychological Advantages of Learning Another Language

Learning another language can promote brain growth, stave off dementia, boost memory, improve attention and more…

Benefits of learning a second language include brain growth, staving off dementia, boosting memory, improving attention and more…

To have another language is to possess a second soul.” –Charlemagne

People used to think that learning two languages created confusion in the mind.

Far better, it was thought, to get one right than bother with two.

An even more extreme and absurd view was that learning two languages caused a kind of schizophrenia or dual personality.

Some studies did seem to back up the idea that learning two languages could be problematic; early researchers noted that bilingual people tended to have smaller vocabularies and slower access to words.

But these myths and minor disadvantages have now been overshadowed by a wave of new research showing the incredible psychological benefits of learning a second language. And these extend way beyond being able to order a cup of coffee abroad or ask directions to your hotel.

1.Brain growth

The fact that language centres in the brain actually grow is one of the major benefits of learning a second language.

The better you learn, the more those vital areas of the brain grow (Mårtensson et al., 2012).

2. Stave off dementia

Bilingualism delays Alzheimer’s disease in susceptible people by as much as five years (Craik et al., 2010). Seems incredible, but the studies are continuing to support this result.

To put this in context: the effect on dementia of learning another language is much greater than anything achievable with the latest drugs.

3. Hear language better

Being bilingual can lead to improved listening skills, since the brain has to work harder to distinguish different types of sounds in two or more languages (Krizman et al., 2012).

4. Become more language sensitive

Infants in bilingual households can distinguish languages they’ve never even heard before (Werker & Sebastian-Galles, 2011).

Just being exposed to the different sounds in, for example, Spanish and Catalan, helps them tell the difference between English and French is another of the benefits of learning a second language.

5. Boost your memory

Babies brought up in a bilingual environment have stronger working memories than those brought up with only one language (Morales et al., 2013).

This means they are better at mental calculation, reading and many other vital skills.

6. Better multi-tasking

Bilingual people can switch from one task to another more quickly.

They show more cognitive flexibility and find it easier to adapt to unexpected circumstances (Gold et al., 2013)

7. Increased attention

Bilinguals have stronger control over their attention and are better able to limit distractions (Bialystok & Craik, 2010).

8. Double the activation

Cognitive boosts, like improved attention and better multi-tasking, may come because bilingual people have both languages activated at the same time, and must continually monitor which one is appropriate (Francis, 1999).

All that switching back and forth confers the benefits of learning a second language.

9. New ways of seeing

Learning a new language can literally change the way you see the world.

Learning Japanese, for example, which has basic terms for light and dark blue, may help you perceive the colour in different ways (Athanasopoulos et al., 2010).

10. Improve your first language

Since learning a second language draws your attention to the abstract rules and structure of language, it can make you better at your first language.

As Geoffrey Willans said: “You can never understand one language until you understand at least two.”

Benefits of learning a second language

These ten are all quite apart from the benefits of immersing yourself in another culture, and of seeing your own culture from the perspective of another.

All told, you may well get something like ‘a second soul’ from learning another language.

[Note: some of these studies relate specifically to those who have learned two languages from very early on, but may also be relevant to new language learners.]

Image credit: Michael Davis-Burchat

Misleading Reporting of Alzheimer’s and Conscientiousness Research

There is some classic misinformation in the reporting of a new Alzheimer’s study on the BBC News website.

BBC News clipping

There is some classic misinformation in the reporting of a new Alzheimer’s study on the BBC News website. Entitled ‘Discipline’ may beat Alzheimer’s the first part of the story suggests the personality variable of conscientiousness might protect against developing Alzheimer’s. The link from the homepage states boldly, “Being conscientious may ward off Alzheimer’s.” In fact this line is a far cry from the study which merely finds a correlation between high conscientiousness and lower levels of Alzheimer’s.

Continue reading “Misleading Reporting of Alzheimer’s and Conscientiousness Research”

Brain Cells Matured in Lab

“US scientists say they have duplicated the generation of new adult brain cells in the lab in a controlled way. It is hoped the technique, tested so far on animal cells, will eventually allow scientists to produce a limitless supply of a person’s own brain cells.”

“It is not the first time that immature stem cells have been manipulated in the laboratory to become brain cells. But the researchers say nobody else has replicated the process of cell maturation that goes on in the brain in such complete and close step-by-step detail before.”

The hope is that the cells can be used in the treatment of dementia, Parkinson’s disease and epilespsy.
BBC News

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