Brain-Derived Neurotrophic Factor Augments Rotational Behavior and Nigrostriatal Dopamine Turnover in Vivo (Nigrostratal Neurons/Parknon Dsease/Neostratum) C
Proc. Natl. Acad. Sci. USA Vol. 89, pp. 11347-11351, December 1992 Neurobiology Brain-derived neurotrophic factor augments rotational behavior and nigrostriatal dopamine turnover in vivo (nigrostratal neurons/Parknon dsease/neostratum) C. ANTHONY ALTAR*, CAROLYN B. BOYLAN*, CARL JACKSON*, SUSAN HERSHENSONt, JAMES MILLERt, STANLEY J. WIEGAND*, RONALD M. LINDSAY*, AND CAROLYN HYMAN* *Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591; and tAmgen, Inc., 1900 Oak Terrace Lane, Thousand Oaks, CA 91320 Communicated by Norman Davidson, August 4, 1992 (receivedfor review April 6, 1992) ABSTRACT Brain-derived neurotrophic factor (BDNF), a embryonic dopaminergic neurons in the absence of glia and member of the nerve growth factor (NGF)-related family of in serum-free conditions (5, 11, 13, 14). Several mitogenic neurotrophins, promotes the survival and differentiation of growth factors, including epidermal growth factor and basic cultured ngal dopamine neurons. Two-week infusions of fibroblast growth factor, also promote the growth of cultured BDNF were made above the right pars compacta of the sub- or transplanted mesencephalic dopamine neurons (15-19). stantia nigra in adult rats. Systemic injection of these a s However, these in vitro and in vivo effects appear to be with (+)-amphetamine, a dopamine-releasing drug, induced 3 mediated via astrocytes (15, 16). or 4 body rotations per minute directed away from the nil It remains unknown whether BDNF exerts neurotrophic infuson site. Neither supranigral NGF nor neocortical BDNF effects on central nervous system neurons in vivo. Injections nfusions induced rotational behavior. Systemic i jections ofthe of 17-I-labeled BDNF into the rat neostriatum (area of ni- postsynaptic dopaine receptor agonist apomorphine did not grostriatal dopamine neuron terminals) result in a pharma- induce rotations in these animals, demonstrating a presynaptic cologically specific retrograde transport of 125I-BDNF to dopamine neuron locus for BDNF action.
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