title: Alpha-synuclein deficiency affects brain Foxp1 expression and ultrasonic vocalization.
abstract: Alpha-synuclein is an abundant protein implicated in synaptic function and plasticity, but the molecular mechanism of its action is not understood. Missense mutations and gene duplication/triplication events result in Parkinson's disease, a neurodegenerative disorder of old age with impaired movement and emotion control. Here, we systematically investigated the striatal as well as the cerebellar transcriptome profile of alpha-synuclein-deficient mice via a genome-wide microarray survey in order to gain hypothesis-free molecular insights into the physiological function of alpha-synuclein. A genotype-dependent, specific and strong downregulation of forkhead box P1 (Foxp1) transcript levels was observed in all brain regions from postnatal age until old age and could be validated by qPCR. In view of the co-localization and heterodimer formation of FOXP1 with FOXP2, a transcription factor with a well established role for vocalization, and the reported regulation of both alpha-synuclein and FOXP2 expression during avian song learning, we performed a detailed assessment of mouse movements and vocalizations in the postnatal period. While there was no difference in isolation-induced behavioral activity in these animals, the alpha-synuclein-deficient mice exhibited an increased production of isolation-induced ultrasonic vocalizations (USVs). This phenotype might also reflect the reduced expression of the anxiety-related GABA-A receptor subunit gamma 2 (Gabrg2) we observed. Taken together, we identified an early behavioral consequence of alpha-synuclein deficiency and accompanying molecular changes, which supports the notion that the neural connectivity of sound or emotion control systems is affected.
authors.affiliation: Section Molecular Neurogenetics, Department Neurology, Goethe University Medical School, Frankfurt am Main, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kurz
authors.forename: M
authors.initials: M
authors.lastname: Wöhr
authors.forename: M
authors.initials: M
authors.lastname: Walter
authors.forename: M
authors.initials: M
authors.lastname: Bonin
authors.forename: G
authors.initials: G
authors.lastname: Auburger
authors.forename: S
authors.initials: S
authors.lastname: Gispert
authors.forename: R K W
authors.initials: RK
authors.lastname: Schwarting
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D014828:Vocalization, Animal; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D051858:Forkhead Transcription Factors; C432917:Foxp1 protein, mouse; C432918:Foxp2 protein, mouse; C546280:Gabrg2 protein, mouse; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D012097:Repressor Proteins; D051844:alpha-Synuclein