Sergio Ojeda

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, transsynaptic 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 part of its research on 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 approaches to identify the mechanisms used by glial cells and neurons to regulate GnRH secretion during sexual development.  They are also investigating the role that epigenetic mechanisms play in the neuroendocrine control of female reproductive development and the contribution of epigenetics to the process by which early-live alterations in the metabolic programming of energy balance affect the timing of female puberty.

Another subject of research by this lab focuses on a neurodevelopmental disorder known as Rett syndrome (RTT).  This is a progressive X-linked neurodevelopmental disorder almost exclusively diagnosed in females.  RTT is characterized by a plethora of manifestations that become apparent within the first year of postnatal life.  Most of these manifestations are neurologic, including loss of speech and acquired motor skills, acquirement of stereotypic hand-wringing movements, autistic behavior, seizures, autonomic dysfunction, irregular breathing, and severe mental retardation.  The Ojeda team is investigating the contribution that a gene, over expressed in the cerebral cortex of RTT patients, has the morphological and behavioral abnormalities seen in RTT.

In addition to these neuroendocrine/neurodevelopmental subjects, the Ojeda team is also investigating the concept that certain genes known to be required for the development of the nervous system contribute to regulating the development, differentiation and function of the ovary. Ojeda and his colleges have shown that the ovary expresses a family of genes encoding trophic factors know as neurotrophins, and demonstrated that these factors are important for the assembly of ovarian follicles and for the acquisition of ovulatory competence. In excess, some of these factors are deleterious to ovarian function and cause cyst formation and ovulation failure.

BIOGRAPHY

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.

KEY PUBLICATIONS

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.

Roth, CL, C Mastronardi, A Lomniczi, H Wright, R Cabrera, AE Mungenast, S Heger, H Jung, C Dubay and SR Ojeda. (2007)  Expression of a tumor-related gene network increases in the mammalian hypothalamus at the time of female puberty. Endocrinology  148:5147-5161.

Deng V, Matagne V, Banine F, Frerking M, Ohliger P, Budden S, Pevsner J, Dissen GA, Sherman LS, and Ojeda SR (2007) FXYD1 is an MeCP2 target gene overexpressed in the brains of Rett syndrome patients and Mecp2-null mice.  Hum Mol Genetics 16:640-650.

Ojeda SR, Dubay C, Lomniczi A, Kaidar G, Matagne V, Sandau US, and Dissen GA. (2010) Gene networks and the neuroendocrine regulation of puberty.  Mol Cell Endocrinol  324:3-11. 

Sandau, US, AE Mungenast Z Alderman SP Sardi, AI Fogel, B Taylor, A-S Parent, T Biederer, G Corfas and SR Ojeda. (2011) SynCAM1, a synaptic adhesion molecule, is expressed in astrocytes and contributes to erbB4 receptor-mediated control of female sexual development   Endocrinology 152:2364-2376. 

Clasadonte, J, P Poulain, NK Hanchate, G Corfas, SR Ojeda and V Prevot. Prostaglandin E2 release from astrocytes triggers gonadotrophin-relasing hormone (GnRH) neuron firing via EP2 receptor activation. Proc Natl, Acad. Sci, 2011 Sept 20; 108(38):16104-16109

See a full listing of Dr. Ojeda's publications.