Intrastriatal infusions of brain-derived neurotrophic factor: retrograde transport and colocalization with dopamine containing substantia nigra neurons in rat.
The pattern of retrogradely transported BDNF, a member of the nerve growth family of neurotrophins, following intrastriatal infusion was immunohistochemically visualized within the rodent central nervous system. Human recombinant BDNF was infused at a rate of 3 micrograms/h for 7 days with an Alzet 2002 minipump prior to sacrifice. Tissue immunohistochemically processed using a turkey anti-BDNF antibody revealed retrogradely transported BNDF within neurons located mainly within the ipsilateral frontoparietal cortex (predominantly layer V), parafascicular and posterior thalamic nuclei, and substantia nigra, pars compacta. Sections dual immunoreacted for BNNF and tyrosine hydroxylase revealed a subpopulation of dopaminergic neurons (approximately 28%) within the pars compacta which contained retrogradely transported BDNF. Experiments in which a mixture of BDNF and the retrograde tracer fluorogold were simultaneously infused for 7 days into the striatum revealed BDNF and fluorogold single-labeled neurons as well as BDNF and fluorogold dual-labeled cells within the substantia nigra, pars compacta. These observations indicate that only a subpopulation of neurons within the substantia nigra retrogradely transport BDNF following intrastriatal infusion and thus only a subpopulation of cells may be responsive to the trophic influences of BDNF. The retrograde transport of trophins, such as BDNF, represents a unique neuroanatomical tool to selectivity map the location of specific neurotrophin-responsive systems. Unraveling the trophic anatomy of BDNF will aid in understanding its role in development, degeneration, and experimental animal models of regeneration providing essential data for its use in clinical neurodegenerative disorders including Parkinson's disease.
Mufson
E J
EJ
Department of Neurological Sciences, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612.
Kroin
J S
JS
Sobreviela
T
T
Burke
M A
MA
Kordower
J H
JH
Penn
R D
RD
Miller
J A
JA
D000818:Animals; D000906:Antibodies; D001370:Axonal Transport; D019208:Brain-Derived Neurotrophic Factor; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000502:physiology*; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D007263:Infusions, Parenteral; D008297:Male; D009414:Nerve Growth Factors / Q000493:pharmacokinetics; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000032:analysis / Q000276:immunology; D013378:Substantia Nigra / Q000033:anatomy & histology / Q000502:physiology*; D014422:Turkeys; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine