title: Brain region-dependent differential expression of alpha-synuclein.
abstract: α-Synuclein, the major constituent of Lewy bodies (LBs), is normally expressed in presynapses and is involved in synaptic function. Abnormal intracellular aggregation of α-synuclein is observed as LBs and Lewy neurites in neurodegenerative disorders, such as Parkinson's disease (PD) or dementia with Lewy bodies. Accumulated evidence suggests that abundant intracellular expression of α-synuclein is one of the risk factors for pathological aggregation. Recently, we reported differential expression patterns of α-synuclein between excitatory and inhibitory hippocampal neurons. Here we further investigated the precise expression profile in the adult mouse brain with special reference to vulnerable regions along the progression of idiopathic PD. The results show that α-synuclein was highly expressed in the neuronal cell bodies of some early PD-affected brain regions, such as the olfactory bulb, dorsal motor nucleus of the vagus, and substantia nigra pars compacta. Synaptic expression of α-synuclein was mostly accompanied by expression of vesicular glutamate transporter-1, an excitatory presynaptic marker. In contrast, expression of α-synuclein in the GABAergic inhibitory synapses was different among brain regions. α-Synuclein was clearly expressed in inhibitory synapses in the external plexiform layer of the olfactory bulb, globus pallidus, and substantia nigra pars reticulata, but not in the cerebral cortex, subthalamic nucleus, or thalamus. These results suggest that some neurons in early PD-affected human brain regions express high levels of perikaryal α-synuclein, as happens in the mouse brain. Additionally, synaptic profiles expressing α-synuclein are different in various brain regions.
authors.affiliation: Department of Basic Geriatrics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Basic Geriatrics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Basic Geriatrics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tsujimura
authors.affiliation: Department of Basic Geriatrics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D016631:Lewy Bodies / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000378:metabolism*; D009830:Olfactory Bulb / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D065842:Pars Compacta / Q000378:metabolism; D051844:alpha-Synuclein / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D051844:alpha-Synuclein
keywords: GAD; Parkinson's disease; RRID: AB_10048713; RRID: AB_2192953; RRID: AB_2199314; RRID: AB_2301751; RRID: AB_390204; RRID: AB_398108; RRID: AB_477019; mouse; synapse; vGluT-1