Johns Hopkins University

Fasgen, Inc.

Gabriele V Ronnett

Solomon H Snyder

Lynda D Hester

Jill Marie Sturdivant

Craig B Warren

Louise D McCullough

Loren Walensky

Jeffrey S Nye

Anne M Cunningham

Felice F Borisy

A method of neuroprotection which comprises administration of an AMPK inhibitor to a patient who is experiencing or has experienced a stroke, the compound being an AMPK inhibitor. Treatments with these agents significantly reduce the size of infarcts, and therefore minimize the loss of brain tissue and neurons. Thus, function can be preserved after stroke or ischemic injury in the brain. Similarly, neuronal loss can be minimized in degenerative diseases that cause neuronal compromise by perturbing energy utilization and availability in neurons.

Method of neuroprotection by pharmacological inhibition of AMP-activated protein kinase

The present invention provides a nucleic acid comprising a sequence that encodes a sperm receptor that is related to, but is different from, a receptor of the odorant receptor family. The present invention also provides a method of obtaining a nucleic acid that comprises a sequence that encodes a sperm receptor, as well as a means of using the elements of the invention in a method of contraception, a method of detecting autoimmune infertility, and a method of affecting fertility.

Sperm receptors

The present invention provides the art with methods for enhancing the sense of smell. The method involves application of an inhibitor of phosphodiesterase to the olfactory epithelium. New inhibitors can be screened using one or more phosphodiesterases isolated from olfactory mucosa. Nebulizers for applying inhibitors to the olfactory mucosa are also provided.

Inhibition of phosphodiesterase in olfactory mucosa

Primary cultures of purified olfactory neurons can be stimulated with physiological levels of odorants. The neurons of the cultures express markers characteristic of mature olfactory neurons in vivo, such as vimentin, olfactory marker protein and neuron-specific enolase. The cultures are useful for screening for odorants and antagonists, as well as for biochemical and physiological studies of olfactory transduction. The olfactory neurons may comprise at least about 85% of cells in the culture. The olfactory neurons demonstrate responsiveness in culture to IBMP, citraliva, and isovaleric acid.

Method of determining odorant compounds and antagonists of odorants

Primary cultures of purified olfactory neurons can be stimulated with physiological levels of odorants. The neurons of the cultures express markers characteristic of mature olfactory neurons in vivo, such as vimentin, olfactory marker protein and neuron-specific enolase. The cultures are useful for screening for odorants and antagonists, as well as for biochemical and physiological studies of olfactory transduction.

Primary culture of olfactory neurons

A method of producing primary cultures of olfactory neurons which are purified from sustentacular cells and basal cells. The neuronal cells demonstrate responsiveness to physiologic levels of odorants and express Olfactory Marker Protein (OMP). The steps required to obtain the primary cultures are:

Method of making primary culture of olfactory neurons

Primary cultures of purified olfactory neurons can be stimulated with physiological levels of ordorants. The neurons of the cultures express markers characteristic of mature olfactory neurons in vivo, such as vimentin, olfactory marker protein and neuron-specific enolase. The cultures are useful for screening for odorants and antagonists, as well as for biochemical and physiological studies of olfactory transduction. The olfactory neurons may contain at least about 95% of cells in the culture. The olfactory neurons demonstrate responsiveness in culture to IBMP, citraliva, and isovaleric acid.

This invention is directed to continuous, non-maligant, neuronal cell lines, the cells of which: a) in the undifferentiated form are essentially free of branched process; b) stain positively for neurofilament protein and neurotransmitters; c) do not stain positively for glial fibrillary acidic protein; and d) in the presence of nerve growth factor differentiate into cells with long branched processes. Derivative cell lines of such cell lines are also contemplated. The cell lines are useful in screening methods for evaluation of chemical and biological compounds as well as for therapeutic uses.

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Baltimore, MD, United States of America

Gabriele V Ronnett