Roberta Diaz Brinton, Ph.D.

Molecular Pharmacology and Toxicology
Department of Biology: Neurobiology

Neurobiology of Learning and Memory

Research conducted in my laboratory investigates the cellular, biochemical and genomic mechanisms underlying plasticity in the nervous system with particular emphasis on neural peptide and neurosteroid factors that influence learning and memory. By exploring how mnemonic factors influence morphological plasticity and the associated biochemical and genomic mechanisms that mediate structural change, we can gain insights into the range of neuronal responses which potentially serve as cellular analogs of learning and memory. The goal of our research is to understand the basic cellular mechanisms involved in learning and memory and to apply these insights to the rational design of therapeutic agents for the treatment of cognitive disorders.

Our research on vasopressin, a neural peptide which can enhance memory function, has revealed by RT-PCR that the mRNA for the vasopressin receptor is expressed in brain regions critical to memory function. We have go on to explore the cellular, biochemical and genomic effector mechanisms associated with vasopressin receptors in the hippocampus and cerebral cortex. Results of these studies have shown that vasopressin acts as a neurotrophic factor for neurons derived from brain regions involved in memory function and induces complex calcium signaling in these cells. In addition, we have found that vasopressin induces immediate early response genes. We are currently investigating vasopressin-induction of novel genes in cortical neurons and vasopressin-induction of growth factor gene expression in cortical glial cells. In addition, we are exploring factors that regulate the expression of the vasopressin receptor in the cerebral cortex and hippocampus.

Our research on neurosteroids has shown that metabolites of the steroid progesterone can induce profound effects upon the outgrowth of neuronal projections as well as protect against epileptic seizure activity. More recently, we have focused on estrogenic steroids and their ability to act as neurotrophic agents for neurons derived from brain regions in learning and memory. Results of these studies have led to the discovery of estrogenic steroids that have a low affinity for the estrogen nuclear receptor but which exert a highly significant enhancement of nerve cell outgrowth. Because memory function is dependent upon neuronal outgrowth and the development of new structural circuits in the brain, these findings are particularly important for the development of therapeutic strategies for the treatment of cognitive decline in aging women and for the prevention of Alzheimer’s Disease in postmenopausal women. The discovery of estrogenic steroids that have a low affinity for the estrogen nuclear receptor and which act as neurotrophic agents are important considerations for reducing the risk of breast and uterine cancer while maintaining cognitive function in postmenopausal women.

Selected Publications

1. Brinton, R.D., Vasopressin in the Mammalian Brain: Neurobiology of a Mnemonic Peptide. Life Science Advances on Neuropeptides, In Press.
2. Brinton, R.D., The Neurosteroid, 3a-hydroxy-5a-pregnan-20-one, Induces Cytoarchitectural Regression In Cultured Fetal Hippocampal Nerve Cells. Journal of Neuroscience, 14(5): 2763-2774, 1994.
3. Brinton, R.D., Profitt, P., Tran, J. and Luu, R., Equilin, a major component of the estrogen replacement therapy, Premarin, increases the growth of neurons from the cerebral cortex. Proceedings of the Fifth International Conference on Alzheimer’s Disease, In Press.