In vitro cell culture findings could lead to novel interventions for schizophrenia

A study recently  has shown how using cultured cells from patients with psychotic disorders, such as schizophrenia, to investigate abnormalities in nerve connections in the brain could lead to new treatments. Strong correlations were observed between the findings in the cells in culture—grown outside the body in a controlled environment—and findings from brain imaging performed on the very same human participants. 

"The findings are important, because if the health of cells in culture reflects the health of the same cells in a human brain, we may be able to create a better model for studying psychotic disorders," said the study's senior author. He said such a model could give researchers a greater capacity to find genetic and biochemical targets in the brain. Using these targets, he said, "could enable us to develop novel and more effective interventions for psychotic disorders."

For their work, the team  drew on studies showing that altered pathways of brain development can be found across most cases of schizophrenia and that inaccurate connections and "leaks" in signaling between nerve cells are a feature of many psychotic disorders. A substance called myelin, produced by cells called oligodendrocytes, serves as a kind of insulation to prevent these leaks. In studies , myelin was measured and found to be reduced in the brain in patients with schizophrenias.

Based on this prior research, the researchers drew on a repository of cell lines they had obtained from patients with psychiatric disorders. These samples were reprogrammed from skin cells into brain-like cells in the laboratory. The reprogrammed cell lines, taken from both ill and healthy patients, produced nerve cells and support cells called glia, including oligodendrocytes, in laboratory cultures. Investigations into these cells revealed significant abnormalities in the development of oligodendrocytes grown from subjects with psychotic disorders.

The research also revealed a strong correlation between the number of oligodendrocytes in culture and the amount of myelin made by these cells in the brains of the same subjects who provided the cells. This finding, Cohen explained, "means that we can now study the causes of the abnormality of myelin that we have observed in living brain tissue in a laboratory setting."

For the researchers, the prospect of using lab cultures to examine differences in the brains of individuals with psychotic illnesses is "an exciting development." For example, the Prof. said, researchers have observed that not all genes and proteins necessary to make oligodendrocytes are affected in these cells, and they can now begin to identify exactly what genes and proteins are different in these cells. It would be impossible, he said, to do these detailed studies in living brain tissue.

Such studies, the researchers believe, could lead to better treatment approaches for individuals with psychotic conditions. "Using in vitro cell cultures to study these abnormalities could help us identify specific genetic and biochemical targets that might be addressed by novel drug treatments, cell transplantation, or other interventions," the Prof. said.

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Sleep 'boosts brain cell numbers'

Scientists believe they have discovered a new reason why we need to sleep - it replenishes a type of brain cell.

Sleep ramps up the production of cells that go on to make an insulating material known as myelin which protects our brain's circuitry.

The findings, so far in mice, could lead to insights about sleep's role in brain repair and growth as well as the disease MS.

Dr  found that the production rate of the myelin making cells, immature oligodendrocytes, doubled as mice slept.

The increase was most marked during the type of sleep that is associated with dreaming - REM or rapid eye movement sleep - and was driven by genes.

In contrast, the genes involved in cell death and stress responses were turned on when the mice were forced to stay awake.

Precisely why we need to sleep has baffled scientists for centuries. It's obvious that we need to sleep to feel rested and for our mind to function well - but the biological processes that go on as we slumber have only started to be uncovered relatively recently.

Growth and repair

Dr said: "For a long time, sleep researchers focused on how the activity of nerve cells differs when animals are awake versus when they are asleep.

"Now it is clear that the way other supporting cells in the nervous system operate also changes significantly depending on whether the animal is asleep or awake."

The researchers say their findings suggest that sleep loss might aggravate some symptoms of multiple sclerosis (MS), a disease that damages myelin.

In MS, the body's immune system attacks and destroys the myelin coating of nerves in the brain and spinal cord.

Future studies could look at whether or not sleep affects the symptoms of MS, says Dr.

Her team is also interested in testing whether lack of sleep, especially during adolescence, may have long-term consequences for the brain.

Sleep appears necessary for our nervous systems to work properly.

Deep sleep coincides with the release of growth hormone in children and young adults. Many of the body's cells also show increased production and reduced breakdown of proteins during deep sleep.

Since proteins are the building blocks needed for cell growth and for repair of damage from factors like stress and ultraviolet rays, deep sleep may truly be "beauty sleep".

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