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 luteinizing hormone-releasing hormone (LHRH), a substance that controls the secretion of reproductive hormones from the pituitary gland. The investigators are using cellular, molecular, genetic and systems biology approaches to identify the mechanisms used by glial cells and neurons to regulate LHRH secretion during sexual development.

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 knowas neurotrophins, and demonstrated that these factors are important for the assembly of ovarian follicles and for the acquisitions 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 and head of 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 Editorial Board members for the journals 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 Biochemical Endocrinology NIH 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

Mastronardi G, Smiley GG, Raber J, Kusakabe T, Kawaguchi A, Matagne V, Dietzel A, Heger S, Mungenast AE, Cabrera R, Kimura S, and Ojeda SR. (2006) Deletion of the Ttf1 gene in differentiated neurons disrupts female reproduction without impairing basal ganglia function.  J Neurosci 26:13167-13179.  PMID:17182767.

Garci-Rudaz C,  Luna F, Tapia V, Kerr B, Colgin L, Galimi F, Dissen GA, Rawlings ND, and  Ojeda SR. (2007) Fxna, a novel gene differentially expressed in the rat ovary at the time of folliculogenesis, is required for normal ovarian histogenesis. Development 134:945-957. PMID:17267443.

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.

Deng V, Matagne V, Banine F, Frerking M, Ohliger P, Budden S, Pevsner J, Dissen GA, Sherman L, 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. PMID:17309881.

Dissen GA, Lomniczi A, Neff TL, Hobbs TR, Kohama SG, Kroenke CD, Galimi F, and Ojeda SR.  (2009) In vivo manipulation of gene expression in non-human primates using lentiviral vectors as delivery vehicles.  Methods 49:70-77. PMID:19559089.