title: A new dopaminergic nigro-olfactory projection.
abstract: Parkinson disease (PD) is a neurodegenerative disorder characterized by massive loss of midbrain dopaminergic neurons. Whereas onset of motor impairments reflects a rather advanced stage of the disorder, hyposmia often marks the beginning of the disease. Little is known about the role of the nigro-striatal system in olfaction under physiological conditions and the anatomical basis of hyposmia in PD. Yet, the early occurrence of olfactory dysfunction implies that pathogens such as environmental toxins could incite the disease via the olfactory system. In the present study, we demonstrate a dopaminergic innervation from neurons in the substantia nigra to the olfactory bulb by axonal tracing studies. Injection of two dopaminergic neurotoxins-1-methyl-4-phenylpyridinium and 6-hydroxydopamine-into the olfactory bulb induced a decrease in the number of dopaminergic neurons in the substantia nigra. In turn, ablation of the nigral projection led to impaired olfactory perception. Hyposmia following dopaminergic deafferentation was reversed by treatment with the D1/D2/D3 dopamine receptor agonist rotigotine. Hence, we demonstrate for the first time the existence of a direct dopaminergic projection into the olfactory bulb and identify its origin in the substantia nigra in rats. These observations may provide a neuroanatomical basis for invasion of environmental toxins into the basal ganglia and for hyposmia as frequent symptom in PD.
authors.affiliation: Department of Neurology, Technical University Munich, 81377, Munich, Germany, guenter.hoeglinger@dzne.de.
authors.forename: Günter U
authors.initials: GU
authors.lastname: Höglinger
authors.forename: Daniel
authors.initials: D
authors.lastname: Alvarez-Fischer
authors.forename: Oscar
authors.initials: O
authors.lastname: Arias-Carrión
authors.forename: Miriam
authors.initials: M
authors.lastname: Djufri
authors.forename: Andrea
authors.initials: A
authors.lastname: Windolph
authors.forename: Ursula
authors.initials: U
authors.lastname: Keber
authors.forename: Andreas
authors.initials: A
authors.lastname: Borta
authors.forename: Vincent
authors.initials: V
authors.lastname: Ries
authors.forename: Rainer K W
authors.initials: RK
authors.lastname: Schwarting
authors.forename: Dieter
authors.initials: D
authors.lastname: Scheller
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D056347:Neuroanatomical Tract-Tracing Techniques; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D056325:Neuronal Tract-Tracers; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D000857:Olfaction Disorders / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D018491:Dopamine Agonists; D056325:Neuronal Tract-Tracers; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine; D016627:Oxidopamine; D004298:Dopamine