Nav: Home

Resynchronizing neurons to erase schizophrenia

September 17, 2018

Schizophrenia, an often severe and disabling psychiatric disorder, affects approximately 1% of the world's population. While research over the past few years has suggested that desynchronization of neurons may be the cause of its neuropsychiatric symptoms, such as memory disorders, hyperactivity or hallucinatory phenomena, the cellular origin of such desynchronization remains poorly understood. Today, a decisive step in understanding this disease has been taken. Researchers at the University of Geneva (UNIGE) have succeeded not only in deciphering a cellular mechanism leading to the desynchronization of neural networks, but also in correcting this organizational defect in an adult animal model, thereby suppressing abnormal behaviours associated with schizophrenia. Results, to be discovered in Nature Neuroscience, that show that a therapeutic intervention is possible at all ages.

Schizophrenia, which clinical manifestations may differ from one patient to another, is a neurodevelopmental disease characterized by many cognitive and behavioural symptoms, including visual or auditory hallucinations, memory and planning issues, or hyperactivity. While the exact cause of this highly disabling disease is not yet known, certain genetic mutations greatly increase its risk. For example, individuals affected by the DiGeorge syndrome are 40 times more likely to develop schizophrenic disorders than the general population. The DiGeorge syndrome, also known as the 22q11 deletion syndrome, is a human genetic abnormality marked by the absence of about thirty genes on one of the two copies of chromosome 22.

"What happens in the brains of patients suffering from these behavioural changes characteristic of the disease? Our aim was not only to understand how their neural networks dysfunctions, but also to figure out whether it was possible to restore their normal functioning, especially in adults," explains Alan Carleton, professor in the Department of Basic Neurosciences at the Faculty of Medicine of the UNIGE, who directed this work.

A question of networks

The Geneva neuroscientists chose to focus on neural networks of the hippocampus, a brain structure notably involved in memory. They studied a mouse model that reproduces the genetic alteration of DiGeorge syndrome as well as some behavioural changes associated with schizophrenia. In the hippocampus of a control mouse, the thousands of neurons that make up the network coordinate according to a very precise sequence of activity, which is dynamic in time and synchronized. However, in the neural networks of their mouse models, the scientists observed something completely different: the neurons showed the same level of activity as in control animals, but without any coordination, as if these cells were incapable of communicating properly with each other. "The organization and synchronization of neural networks is achieved through the intervention of subpopulations of inhibitory neurons, including parvalbumin neurons,» says Carleton. "However, in this animal model of schizophrenia, these neurons are much less active. Without proper inhibition to control and structure the electrical activity of other neurons in the network, anarchy rules. "

Restoring neural order, even in adulthood

The second step was to try to restore the synchronization necessary for neural networks to function properly. To do this, the scientists specifically targeted the parvalbumin neurons of the hippocampus. By stimulating these dysfunctional inhibitory neurons, they managed to restore the sequential organization and normal functioning of neural networks. Similarly, they were able to correct some behavioural abnormalities in these schizophrenia mouse models, suppressing both hyperactivity and memory deficit.

These very positive results suggest that a therapeutic intervention is possible, even in adulthood. "This is really essential. Indeed, schizophrenia develops in late adolescence, although the neural alterations are most likely present since the neurodevelopmental stage. According to our results, reinforcing the action of a poorly active inhibitory neuron, even after the brain has developed, could be sufficient to restore the proper functioning of these neural networks, thus making certain pathological behaviours disappear."

Current treatments for schizophrenia are primarily based on the administration of antipsychotic drugs targeting the dopaminergic and serotoninergic systems. In spite of their positive effect on hallucinatory symptoms, they remain less effective to improve many symptoms, and in particular cognitive symptoms. An approach aiming at overcoming the defect of parvalbumin neurons to increase their inhibitory effect therefore appears to be a promising target; nevertheless, time will be needed before a treatment based on this strategy is developed. The neuroscientists now want to confirm their results by extending their research to schizophrenia resulting from genetic alterations different from those of DiGeorge syndrome.
-end-


Université de Genève

Related Schizophrenia Articles:

Dietary supplement may help with schizophrenia
A dietary supplement, sarcosine, may help with schizophrenia as part of a holistic approach complementing antipsychotic medication, according to a UCL researcher.
Schizophrenia: Adolescence is the game-changer
Schizophrenia may be related to the deletion syndrome. However, not everyone who has the syndrome necessarily develops psychotic symptoms.
Study suggests overdiagnosis of schizophrenia
In a small study of patients referred to the Johns Hopkins Early Psychosis Intervention Clinic (EPIC), Johns Hopkins Medicine researchers report that about half the people referred to the clinic with a schizophrenia diagnosis didn't actually have schizophrenia.
The ways of wisdom in schizophrenia
Researchers at UC San Diego School of Medicine report that persons with schizophrenia scored lower on a wisdom assessment than non-psychiatric comparison participants, but that there was considerable variability in levels of wisdom, and those with higher scores displayed fewer psychotic symptoms.
Recognizing the uniqueness of different individuals with schizophrenia
Individuals diagnosed with schizophrenia differ greatly from one another. Researchers from Radboud university medical center, along with colleagues from England and Norway, have demonstrated that very few identical brain differences are shared amongst different patients.
Resynchronizing neurons to erase schizophrenia
Today, a decisive step in understanding schizophrenia has been taken.
Genetics researchers close in on schizophrenia
Researchers at the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University have discovered 50 new gene regions that increase the risk of developing schizophrenia.
Looking for the origins of schizophrenia
Schizophrenia may be related to neurodevelopment changes, including brain's inability to create the appropriate vascular system, according to new study resulted from a partnership between the D'Or Institute for Research and Education, the University of Chile and the Federal University of Rio de Janeiro (UFRJ).
Researchers uncover novel mechanism behind schizophrenia
An international team of researchers led by a Case Western Reserve University School of Medicine scientist has uncovered a novel mechanism in which a protein--neuregulin 3--controls how key neurotransmitters are released in the brain during schizophrenia.
A new genetic marker for schizophrenia
Japanese scientists find a rare genetic variant that shows strong association with schizophrenia.
More Schizophrenia News and Schizophrenia Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.