The mammalian brain is made up of millions of cells that produce substances of diverse chemical composition. Some of these cells, known as neurons, release their products into synapses, highly specialized structures that link one neuron to another and permit the function of one cell to be directly influenced by multiple other neurons. In addition, non-neuronal cells, called glial cells, produce a variety of substances that affect the functions of neurons without the mediation of a synapse. Glial cells also secrete growth factors required for the integrity of neuronal function, trans-synaptic communication and the survival of neurons.
Sergio Ojeda and his collaborators seek to understand the process by which the brain controls the initiation of mammalian puberty. An important goal in their laboratory is to gain insights into the molecular and genetic mechanisms underlying deranged sexual development, particularly sexual precocity and delayed puberty of cerebral origin. Ojeda's team focuses on identifying molecules responsible for the interactions that occur between neurons and glial cells in the hypothalamus, a region in the base of the brain that controls several bodily functions, including hormone secretion, reproduction, response to stress, feeding and sex behavior. One group of hypothalamic neurons produces gonadotropin-releasing hormone (GnRH), a substance that controls the secretion of reproductive hormones from the pituitary gland.
The investigators are using cellular, molecular, genetics and systems biology strategies, in addition to high-throughput approaches and computational biology methods to develop three interrelated concepts: 1) That mammalian puberty is controlled by genetic networks that, operating within different cell contexts in the neuroendocrine brain, coordinate the activity of GnRH neurons at puberty, 2) That these networks are controlled at the transcriptional level by a repressive mechanism exerted by discrete subsets of gene "silencers", and 3) That this transcriptional regulation is under epigenetic control, i.e. a mechanism by which environmental factors (such as nutrition, man-made chemicals, changes in light/dark cycle, etc.) regulate gene activity without modifying the actual sequence of encoding DNA.
Sergio Ojeda is a senior scientist in the Division of Neuroscience. He is also professor of physiology and of cell biology in the OHSU School of Medicine. He received his D.V.M. degree from the University of Chile in 1968 and his postdoctoral training in neuroendocrinology between 1972-1974 at the University of Texas Southwestern Medical Center at Dallas. Ojeda was professor of physiology at the same institution when he was appointed to the Center in 1987. He has served as Associate Editor for the journals Endocrinology and Neuroendocrinology, and as an Editorial Board member for the American Journal of Physiology. He currently serves on the Editorial Board of Endocrinology, Neuroendocrinology, J. Neuroendocrinology, and Methods in Neuroscience, and is Associate Editor for Neuroendocrinology. Dr. Ojeda has served as a regular member of the NIH Biochemical Endocrinology Study Section, the NIH Population Research Committee, the NIH National Institute of Child Health Development Advisory Council and the NIH Council of Councils. He is currently a member of the NIH Integrative Clinical Endocrinology and Reproduction Study Section.
Heger S, Mastronardi C, Dissen GA, Lomniczi A, Cabrera R, Roth CL, Jung H, Galimi F, Sippell W and Ojeda SR. (2007) Enhanced at Puberty1 (EAP1) is a new transcriptional regulator of the female neuroendocrine reproductive axis. J Clin Invest. 117:2145-2154. PMID: 17627301. PMCID: PMC1906733.
Gray SJ, Matagne V, Bachaboina L, Yadav S, Ojeda SR and Samulski RJ. (2011) Preclinical differences of intravascular AAV9 delivery to neurons and glia: a comparative study of adult mice and non-human primates. Mol Ther. 19(6):1058-1069. PMID: 21487395. PMCID: PMC3129805.
Mueller JK, Dietzel A, Lomniczi A, Loche A, Tefs K, Kiess W, Danne T, Ojeda SR and Heger S. (2011) Transcriptional regulation of the human KiSS1 gene. Mol Cell Endo. 342(1-2):8-19. PMID: 21672609. PMCID: PMC3148268.
Clasadonte J, Poulain P, Hanchate NK, Corfas G, Ojeda SR and Prevot V. (2011) Prostaglandin E2 release from astrocytes triggers gonadotrophin-releasing hormone (GnRH) neuron firing via EP2 receptor activation. Proc Natl Acad Sci. 2011 Sep 20; 108(38):16104-16109. PMID: 21896757. PMCID: PMC3179065.
Sandau US, Alderman Z, Corfas G, Ojeda SR and Raber J. (2012) Astrocyte-specific disruption of SynCAM1 signaling results in ADHD-like behavioral manifestations. PLoS One. 7(4):e36424. PMID: 22558465. PMCID: PMC3340339.
Lomnizci A, Loche A, Castellano JM, Ronnekliev O, Bosh M, Kaidar G, Knoll JG, Wright H, Pfeifer GP and Ojeda SR. (2013) Epigenetic control of female puberty. Nature Neuroscience. 16:281-289. PMID: 23354331. PMCID: PMC3581714.
See a full listing of Dr. Ojeda's publications