title: Differential expression of alpha-synuclein in hippocampal neurons.
abstract: α-Synuclein is the major pathological component of synucleinopathies including Parkinson's disease and dementia with Lewy bodies. Recent studies have demonstrated that α-synuclein also plays important roles in the release of synaptic vesicles and synaptic membrane recycling in healthy neurons. However, the precise relationship between the pathogenicity and physiological functions of α-synuclein remains to be elucidated. To address this issue, we investigated the subcellular localization of α-synuclein in normal and pathological conditions using primary mouse hippocampal neuronal cultures. While some neurons expressed high levels of α-synuclein in presynaptic boutons and cell bodies, other neurons either did not or only very weakly expressed the protein. These α-synuclein-negative cells were identified as inhibitory neurons by immunostaining with specific antibodies against glutamic acid decarboxylase (GAD), parvalbumin, and somatostatin. In contrast, α-synuclein-positive synapses were colocalized with the excitatory synapse marker vesicular glutamate transporter-1. This expression profile of α-synuclein was conserved in the hippocampus in vivo. In addition, we found that while presynaptic α-synuclein colocalizes with synapsin, a marker of presynaptic vesicles, it is not essential for activity-dependent membrane recycling induced by high potassium treatment. Exogenous supply of preformed fibrils generated by recombinant α-synuclein was shown to promote the formation of Lewy body (LB) -like intracellular aggregates involving endogenous α-synuclein. GAD-positive neurons did not form LB-like aggregates following treatment with preformed fibrils, however, exogenous expression of human α-synuclein allowed intracellular aggregate formation in these cells. These results suggest the presence of a different mechanism for regulation of the expression of α-synuclein between excitatory and inhibitory neurons. Furthermore, α-synuclein expression levels may determine the efficiency of intracellular aggregate formation in different neuronal subtypes.
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 Neurology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, Japan.
authors.forename: Harutsugu
authors.initials: H
authors.lastname: Tatebe
authors.affiliation: Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Miyata
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, Japan ; Department of Molecular Pathobiology of Brain Diseases, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tokuda
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Mizuno
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; D002478:Cells, Cultured; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010320:Parvalbumins / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D010320:Parvalbumins; D050598:Vesicular Glutamate Transport Protein 1; D051844:alpha-Synuclein; D013004:Somatostatin; D005968:Glutamate Decarboxylase