Schizophrenia and the Dysfunction of Glial Cells

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young woman looking fine on the outside but unwell in her emotions and mental state

Around the world, at least 21 million people have schizophrenia. As Nobel laureate Eric Kandel wrote, “schizophrenia is a complex disorder affecting numerous regions of the brain and ultimately undermining the integrity of the self.” The self, as Kandel explains, is never the same. Let’s take a deeper look into the causes and effects of this disorder.

The Many Faces of Schizophrenia

For many family members, it is difficult to see their loved ones suffer from such a disorder. The first visible effects of schizophrenia are social withdrawal and the lack of motivation. Psychiatrists refer to these as the negative effects, but then, well past the teenage years, certain positive effects start to kick in; hallucinations and delusion start to take over and loved ones that once were thought of being shy or nervous can begin to change drastically.

The great neurologist Oliver Sacks gave a vivid account on how life is around a loved one with schizophrenia. His brother, Michael Sacks, suffered from such disease and in Oliver Sacks’s first memoir, Uncle Tungsten, he described how life changed for his family when Michael was diagnosed:

“My Auntie Len, who was staying with us, spied Michael as he came, half naked, from the bath. ‘Look at his back!’ she said to my parents, ‘it’s full of bruises and weals!’ If this is happening to his body,’ she continued, ‘what is happening to his mind?’ My parents seemed surprised, said that they had noticed nothing amiss, that they thought that Michael was enjoying school, had no problem and was ‘fine.’

Soon after this, when he was fifteen, Michael became psychotic. He felt a magical and malignant world was closing about him. He came to believe that he was ‘the darling of a flagello-maniac God,’ as he put it, subject to the special attentions of ‘a sadistic Providence.’ Messianic fantasies or delusions appeared at the same time—if he was being tortured or chastised, this was because he was the (or might be) the Messiah, the one for whom we had waited so long. Torn between bliss and torment, fantasy and reality, feeling he was going mad (or perhaps so already), Michael could no longer sleep or rest, but agitatedly strode to and fro in the house, his feet, glaring, hallucinations, shouting.”

Dopamine in excess

Excessive dopamine, the “feel-good hormone,” is the key player in schizophrenia. As Kandel explains, “During pregnancy environmental factors, such as nutritional deficits, infections, or exposure to stress and toxins, may interact with the genes to increase the risk that the fetus will develop abnormality functioning of dopaminergic pathways.” This excess of dopamine release was the key for understanding schizophrenia for many scientists, so they targetted brain regions like the substantia nigra and ventral tegmental area (pathways for the release of dopamine) with the hope of finding a solution.

In 2017, scientists found out that excess of dopamine was not the only thing to worry about. University of Copenhagen scientists found that “genetic defects may damage the supporting cells of the brain—the glial cells—which may lead to some brain disorders, including schizophrenia.”

What are Glial Cells?

The term glia means “neuro glue,” and these cells are found adhered to neurons, the cells of the nervous system. R. Douglas Fields, one of the prime experts in such cells, explains, “For decades these glial cells had been considered little more than mental bubble wrap, connective tissue that physically and perhaps nutritionally supported the neurons…” Glial cells outnumbered neurons six to one and can differ in numbers across the nervous system. One of the most well-known sort of glia cells are Oligodendrocytes, which form an octopus-shaped attached to the axon of the neuron. As Fields explains, “Without these octopus glial, the nervous impulses will fail and the brain circuits become powerless.”

Another type of glia cells, Astrocytes, are also crucial to the development of the brain and the nervous system. Tasks like maintaining homeostasis, regulating the blood flow, and playing a vital role in information processing in the synapsis make astrocytes an intriguing type of glial cell. Because of the purpose of this type of glia cells, scientist has found certain diseases linked to them. One of the most famous is Alexander disease, a rare neurological disorder that develops early in the life of humans, involving enlarged brains and constant seizures. The scientist that first described the disease showed that the disorder was connected to the degeneration of astrocytes.

The scientists at Copenhagen found that astrocytes and oligodendrocytes played a key role in schizophrenia when showing dysfunctional development. As neuroscientist Steve Goldman explains, “It was through studies of mice with human glial cells that we succeeded in testing how dysfunctional glial cells may cause abnormalities in the formation of the brain’s neural networks, which may, in turn, cause severe anxiety, anti-social behaviour and severe sleep problems.”

Schizophrenia is not the only problem that includes malfunction of the glial cells. Last month, these same scientists found that the dysfunction in the maturation and development of glial cells contributed to the development of Huntington’s Disease. With the finding, it seems that glial cells when dysfunctional don’t just affect schizophrenia and Huntington’s disease, but many neurodegenerative diseases. In the past, abundant astrocytes (glial cells), were observed in patients with multiple sclerosis.

Last Word on Glial Cells and Neurodegenerative Diseases

These findings are key because they shed light on how essential glial cells are to the development of the brain. Moreover, this gives scientist a new way of approaching many of these neurodegenerative diseases. Already, experts on the field of stem-cells are looking for how to tackle such problems. In 2016, the Copenhagen group experimented with glial cell transplants, looking for a cure for Huntington’s disease. Understanding how glial cells affect the brain could unlock much for neuroscientists in the future.

For more about the brain, check out LWOS life: Science & Technology.

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