San Antonio, Texas (Oct. 10, 2017) - Neuropsychiatric disorders like bipolar disorder, major depressive disorder, schizophrenia, post-traumatic stress disorder, and Alzheimer's and Parkinson's diseases are often correlated with changes in the size and shape of the brain. Texas Biomedical Research Institute Associate Scientist Melanie Carless, Ph.D., has been funded by the National Institute of Mental Health, part of the National Institutes of Health, to identify microRNA biomarkers in the blood and cerebrospinal fluid (clear fluid in the brain and spinal cord) that are associated with these changes in the brain, using a non-human primate model.
"These biomarkers may reveal something about how neuropsychiatric diseases develop," Dr. Carless explained.
The 2-year, $521,848 project focuses on microRNAs, which are small molecules that influence gene and protein expression. MicroRNAs can be packaged inside exosomes, small vesicles that are secreted by different organs and tissues, and transported by blood and cerebrospinal fluid. By studying easily accessible peripheral tissues, such as blood, researchers can gain insight into changes that might be occurring within the brain.
In the first part of the project, Dr. Carless will validate the findings of previous research investigating blood microRNAs associated with changes in brain structure in humans. She plans to use baboons, which are similar to humans in many respects, to identify correlations between microRNAs in the blood or cerebrospinal fluid and structural variation in the brain.
The baboons in the study will include young and old animals as well as animals predisposed to epilepsy or cognitive deficits. Their brains will be measured with magnetic resonance imaging. Dr. Carless will extract microRNAs from the blood and cerebrospinal fluid to assess correlations with brain changes.
In the second part of the project, Dr. Carless will study microRNAs inside the brain regions of interest, such as the amygdala and hippocampus, to see if expression of brain microRNAs are correlated with those in blood and cerebrospinal fluid.
"If the blood and brain microRNA profiles are correlated, that gives you an indication that those microRNAs are not just easy to detect peripherally, but might also be important in disease pathology," Dr. Carless said.
Correlating blood and brain microRNAs is important for matching up blood-based studies with tissue-based studies in humans. Studies on post-mortem human brain tissues are constrained by small sample sizes (and limited statistical power to detect significant effects). In contrast, in living populations, it is possible to collect blood samples from thousands of individuals, but difficult to study brain tissue directly. These baboon studies are the key for linking changes in the blood and in the brain tissue and may indicate the potential of baboons for preclinical studies of neuropsychiatric diseases.
Dr. Carless envisions that these studies will establish baboons as a better model for testing novel neuropsychiatric treatments. Currently, the success rate for clinical trials of neuropsychiatric drugs hovers around only 8 percent, and the high failure rate is attributed in part to inadequate preclinical models. These baboon studies could bridge that gap, ultimately accelerating the development and FDA-approval process of novel treatments.
The project is being fully supported by the National Institute of Mental Health of the NIH under Award Number R21MH114154.
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