Fig. 1.

Hyperactivity is reversed by paraquat treatment in A30P mice with site-specific expression in the OB. a, b A30P α-synucleinopathy led to olfactory DA deficiency in absence of DAergic cell-death, elevated midbrain DA levels and an associated higher reactive phenotype in A30P mice [71]. Neurochemical changes and phenotype appear to be related to young age in several other mice with widespread α-syn expression [43, 44, 81] and may associate with higher reactivity to mild stress in early PD. Exposure to paraquat potentially exacerbates α-syn-induced toxicity in olfactory DAergic neurons and if leading to changes in phenotype and striatal DAergic tone, further supporting a potential regulative role of OB in the striatal DAergic activity. c Representative images of sagittal brain sections of A30P mice stained with anti-human α-syn antibody. Predominant expression was observed in the GL. Dox-treated mice show strong suppression of immunoreactivity. d Experimental design. The A30P+D and A30P+D+P received 2 mg/ml doxycycline (dox, D) during all the experimental period to suppress A30P expression. After 4 weeks, mice were randomized into two treatment groups receiving either paraquat (P) or saline. Groups were behaviorally tested prior (OF1) and after P treatment (OF2). e Horizontal and vertical (rearing) open field activity was recorded over 10 min. A30P mice are hyperactive compared to controls without expression (A30P+D and non-transgenic controls; Ntg). Horizontal activity and rearing was strongly reduced after paraquat treatment and when compared to dox-treated mice (A30P+P+D). Mice did not display differences in anxiety, as thigmotaxis (expressed in percent of time) was unchanged among groups. The data are mean ± SEM. *p < 0.05, **p < 0.01 A30P vs. A30P+D or A30P+P vs. A30P+D+P. ^§§§p < 0.001 A30P+P vs. A30P. Scale bar in overviews: 3 mm, left panel 60 μm