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Fig. 3 | Translational Neurodegeneration

Fig. 3

From: Constipation, deficit in colon contractions and alpha-synuclein inclusions within the colon precede motor abnormalities and neurodegeneration in the central nervous system in a mouse model of alpha-synucleinopathy

Fig. 3

Colonic contractile activity is impaired in presymptomatic αS Tg mice from 3 months of age. Electrical stimulation (ES) of intestinal tissues shows a reduced response for the colon longitudinal (L) and circular (C) smooth muscles in Tg mice already at 3 months but not for the ileum. The reduced contraction was mainly due to a decreased cholinergic transmission and exacerbated with age. Recordings were performed in αS Tg mice and nTg littermate controls in colon (a, b, c, d, e) and ileum (f). a, f Effects of ES (↑ = ES, 10 Hz) on the contractile activity of colonic (a) or ileal (f) preparations maintained in standard Krebs solution in order to register the overall response. b Effect of selective ES (↑ = ES, 10 Hz) of the inhibitory nitrergic pathway on the activity of colonic longitudinal and circular muscle in order to record nitrergic-induced response. Colonic preparations were maintained in Krebs solution containing guanethidine, L-732,138, GR159897, SB218795 and atropine. c Effect of selective ES (↑ = ES, 10 Hz) of the excitatory cholinergic system on the activity of colonic muscle in order to record cholinergic-induced contractions. Colonic sections were maintained in Krebs solution containing L-NAME, guanethidine, L-732,138, GR159897, and SB218795. d Effect of selective ES (↑ = ES, 10 Hz) of the excitatory tachykinergic pathway on the activity of colonic muscle to record NK1-mediated tachykinergic contractions. Colonic preparations were maintained in Krebs solution containing L-NAME, guanethidine, GR159897, SB218795, atropine. e Effects of carbachol (↑ = Cch; 10 μM) stimulation on the activity of colonic preparations in order to record myogenic response in absence of neurogenic stimulation. Colonic preparations were maintained in Krebs solution containing tetrodotoxin. Tracings in the inset on the top of each panel display the contractile responses to ES, as raw data. Values on graphs are expressed as % relative to controls and are given as the mean ± SEM (n = 8 per group). * p < 0.05; **** p < 0.0001, two-way ANOVA followed by Fischer’s LSD test

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