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Abstract

The present invention relates to neuronal formation and methods of treating diseases characterized by abnormalities in the activity of dopaminergic (DA) and serotonergic (5HT) neurons. In particular, the invention relates to a method of forming serotonergic neurons in vitro by contacting neuroprogenitor cells to an effective amount of native sequence, variants and functional fragments of FGF-4, FGF-8 and Shh. Additionally, disclosed is a method for forming dopaminergic neurons by contacting neuroprogenitor cells to an effective amount of FGF-8 and Shh. Further described are compositions, cell culture compositions and medical devices which contain sufficient amount of FGF-8, Shh or FGF-8, Shh and FGF-4 to stimulate differentiation into dopaminergic or serotonergic neurons, respectively. Further described are methods of using serotoneurgic neurons to treat disorders relating to food intake, hormone secretion, stress response, pain and immune function, sexual activity, cardiovascular function and temperature regulation, in particular, depression, proclivity to suicide, violent aggressive behavior, obsessive-compulsive behavior and anorexia/bulimia and schizophrenia. Further described are methods of using dopaminergic neurons to treat disorders relating postural reflexes, movement and reward-associated behaviors, specifically, Parkinson's disease, schizophrenia and drug addiction. Further described is the coadministration of a neuronal survival factor, for example, NGF, CNTF, BDNF, NT-3, NT-4, aFGF, IL-1.beta., TNF.alpha., IGF-1, IGF-2, TGF-.beta., TGF-.beta.1 or skeletal muscle extract.

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First Claim