Brain cell malfunction linked to schizophrenia
London: Defect in certain portions of protein that package DNA is the root cause of Schizophrenia and the deficit is especially pronounced in younger people, a new study has suggested.
Scientists at The Scripps Research Institute have discovered that DNA stays too tightly wound in certain brain cells of schizophrenic subjects.
The findings suggest that drugs already in development for other diseases might eventually offer hope as a treatment for schizophrenia and related conditions in the elderly.
Schizophrenia is a potentially devastating mental disorder associated with hallucinations, delusions, and emotional difficulties, among other problems.
“We’re excited by the findings,” said Scripps Research Associate Professor Elizabeth Thomas, a neuroscientist who led the study,
“and there’s a tie to other drug development work, which could mean a faster track to clinical trials to exploit what we’ve found.”
Over the past few years, researchers have increasingly recognized that cellular-level changes not tied to genetic defects play important roles in causing disease.
There is a range of such so-called epigenetic effects that change the way DNA functions without changing a person’s DNA code.
One critical area of epigenetic research is tied to histones. These are the structural proteins that DNA has to wrap around.
Histone “tails” regularly undergo chemical modifications to either relax the DNA or repack it. When histones are acetylated, portions of DNA are exposed so that the genes can be used.
If portions of DNA remain closed when they shouldn’t because histones are not acetylated properly, then genes can be effectively turned off when they shouldn’t be with any number of detrimental effects.
Numerous research groups have found that altered acetylation may be a key factor in other conditions, from neurodegenerative disorders such as Huntington’s disease and Parkinson’s disease to drug addiction.
Working with lead author Bin Tang, a postdoctoral fellow in her lab, and Brian Dean, an Australian colleague at the University of Melbourne, Thomas obtained post-mortem brain samples from schizophrenic and healthy brains.
Many researchers feared that histones and DNA bonds were disrupted in the brain after death. However, Thomas’s group was able to develop a technique for maintaining the histone-DNA interactions.
Compared to healthy brains, the brain samples from subjects with schizophrenia showed lower levels of acetylation in certain histone portions that would block gene expression. Another critical finding was that in younger subjects with schizophrenia, the problem was much more pronounced.
Based on the more pronounced results in younger brains, Thomas believes that treatment with histone deacetylase inhibitors might well prove helpful in reversing or preventing the progression of the condition, especially in younger patients.
Current drugs for schizophrenia tend to treat only certain symptoms, such as hallucinations and delusions, and the drugs have major side effects including movement problems, weight gain, and diabetes.
If deacetylase inhibitors effectively treat a root cause of the disease and prove sufficiently non-toxic, they might improve additional symptoms and provide a major expansion of treatment options.
The study has been published in the new Nature journal, Translational Psychiatry.