Proteomics has had much less traction in neuroscience research because the exact molecular pathways of our basic cognitive functions remain elusive and the neurobiological pathophysiology for the majority of brain diseases is poorly understood.1 This makes biomarker validation a challenge in neuroscience.
Having said that, there are researchers applying proteomics technology to neuroscience research with some success in search of a translational biomarker for their respective brain diseases. In January this year, Nilsson et al.2 investigated the role of the hypothalamic-pituitary-adrenal (HPA) axis in depression. Depression results in more than $31 billion of lost productive time in the U.S. and is also the principal cause of 30,000 suicides in the each year.3 There is no doubt that improvements in treatment of mental illness would be of significant benefit. A biomarker for depression could be applied to address the time lag between commencement of treatment and its therapeutic effects.
Nilsson et al. approached their study using the common tricyclic antidepressant, Imipramine, because of the known effects that this drug has on the HPA axis. Mice received intraperitoneal injections for 21 days or on a single day. Hypothalamic samples were then extracted, and peptide identification was was done using mass spectrometry to identify and quantify hypothalamic neuropeptides. They were able to identify several candidates for potential use as translational biomarkers. Among those were peptides derived from chromogranin B. In addition, experiments identified SRIF as a biomarker, a peptide that has previously been implicated in psychiatric diseases. Understanding its mechanism may provide further clues for identifying a translational biomarker to counter depressive symptoms and, in fact, other mental illness.
As our understanding of the human brain continues to develop with the aid of technology, the application of proteomics to this field will certainly expand. Neuropeptides play a vital role in neuronal communication and, without a doubt, will subsequently lead to discovery of a translational biomarker for a multitude of human brain disorders.
1. Filiou, M.D., et al. (2012) ‘To label or not to label: Applications of quantitative proteomics in neuroscience research‘, Proteomics, 12 (4-5), (pp. 736-747)
2. Nilsson, A., et al. (2012) ‘Neuropeptidomics of mouse hypothalamus after imipramine treatment reveal somatostatin as a potential mediator of antidepressant effects‘, Neuropharmacology, 62 (1), (pp. 347-357)
3. Mental Health America, http://www.nmha.org/go/state-ranking