Elena Sidorova-Darmos BSc, MSc, PhD
Postdoctoral Research Fellow, Krembil Research Institute
Supervisor: Dr. James Eubanks
Recently, much progress has been made in our understanding of sex differences in neurobiology and how these dissimilarities can contribute to disease manifestation and outcome. My ongoing research has found that a mitochondrial enzyme called Sirtuin-3 (SIRT3) may play a sex-specific role in several neurodegenerative and neuropsychiatric conditions. In genetic mouse models lacking SIRT3 only female mice displayed mania-like behavioural phenotype. In fact, mania is a key characteristic of a number of neurological and neuropsychiatric disorders, such as Alzheimer’s disease, bipolar disorder, schizophrenia and attention deficit hyperactivity disorder. Thus, SIRT3 may be a common factor in these different conditions. Consistent with current literature, this research demonstrates that neuropsychiatric and neurological disorders involving a mania-like phenotype may be sex-dependent as they are more prevalent in females. My studies show that SIRT3 may represent a new therapeutic target for these conditions and further supports the importance for sex-specific diagnosis. Currently, our laboratory has two publications within this area of focus that are ready for submission.
Keywords: mitochondria, oxidative stress, central nervous system, neurodegenerative disease
What sparked your interest in science or in your specific research area?
I have always believed the brain to be the most intricate and captivating organ in the human body. After all, it is the only organ in the body that named itself. Its interwinding electrical highways carry our thoughts, memories, perceptions and experiences, all of which are established and governed by genetic and cellular underpinnings. What captivated me the most, however, was that these predetermined roads can often fail us. The consequences of trauma, illness, genetic predisposition or even experience can change us as a person in an instant. This very humanizing aspect of the working brain propelled me to become a neuroscientist.
How will your research improve patient care or impact public health?
Collectively, my research adds to the growing body of research that is focused on investigating sex-associated physiological differences. The one-size-fits-all framework for gathering data is now outdated; clinical researchers must retool their efforts by including the analysis of sex effects—an important approach that will enable us to uncover the mechanisms and molecular pathways that underly sex-differences. Ultimately this will help patients by enabling better, more customized, diagnoses and improved treatment outcomes.
Sidorova-Darmos, E., Sommer, R., Eubanks, J.H. (2018). The Role of SIRT3 in the Brain Under Physiological and Pathological Conditions. Frontiers of Cell Neuroscience. 25:12:196.
Sidorova-Darmos E., Wither R., Shulyakova N., Fisher C., Ratnam M., Aarts M., Lilge L., Monnier P., Eubanks J. (2014) Differential expression of sirtuin family members in the developing, adult, and aged rat brain. Frontiers in Aging Neuroscience. 6:333.
Shulyakova N., Sidorova-Darmos E., Fong J., Zhang G., Mills L., Eubanks J. (2014) Over-expression of the Sirt3 sirtuin Protects neuronally differentiated PC12 Cells from degeneration induced by oxidative stress and trophic withdrawal. Brain Research. 1587:40-53.