A new dopaminergic nigro-olfactory projection

作者：Hoeglinger Guenter U; Alvarez Fischer Daniel; Arias Carrion Oscar; Djufri Miriam; Windolph Andrea; Keber Ursula; Borta Andreas; Ries Vincent; Schwarting Rainer K W; Scheller Dieter; Oertel Wolfgang H

来源：Acta Neuropathologica, 2015, 130(3): 333-348.

DOI：10.1007/s00401-015-1451-y

• Parkinson disease
• Braak stages
• Neurodegeneration
• Olfactory perception
• Hyposmia
• Olfactory bulbectomy

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.

• 出版日期2015-9