Research Paper Volume 13, Issue 16 pp 20319—20334

Inhibition of endoplasmic reticulum stress reverses synaptic plasticity deficits in striatum of DYT1 dystonia mice

Altered molecular markers and morphology of synapse in Tor1a+/- mice. (A) Representative confocal images from two SPNs recorded in Tor1a+/- and Tor1a+/+ slices (scale bar: 10 μm). Recording electrodes were filled with biocytin (pink) and SPNs were immunolabelled with anti-ENK (green) and anti-DARPP-32 (red). ENK-negative SPNs from Tor1a+/- slices failed to induce LTD. (B) WB analysis for p-GluA1 (Ser845), GluA1, GluA2, NMDAR2A, NMDAR2B, PSD-95 and α-tubulin in Tor1a+/- and age-matched Tor1a+/+ mice. (C) Histogram showed the quantification of protein levels following normalization on α-tubulin in Tor1a+/- and age-matched Tor1a+/+ mice. All values are mean ± SEM expressed as % of Tor1a+/+ mice. (D) Representative images showed spine morphology of Tor1a+/- and age-matched Tor1a+/+ mice (scale bar: 10 μm). (E) Histogram represented dendritic spine density in Tor1a+/- and Tor1a+/+ SPNs. Tor1a+/- SPNs exhibited an overall decrease of dendritic spine density (PF, G) Histograms showed the quantification of dendritic spine size (F, spine length and head width) and dendritic spine type (G, mushroom, stubby, thin) in Tor1a+/- and age-matched Tor1a+/+ mice. A larger number of mushroom-type spines and a concomitant smaller number of stubby-type spines were found in Tor1a+/- SPNs (both PP

Figure 2. Altered molecular markers and morphology of synapse in Tor1a+/- mice. (A) Representative confocal images from two SPNs recorded in Tor1a+/- and Tor1a+/+ slices (scale bar: 10 μm). Recording electrodes were filled with biocytin (pink) and SPNs were immunolabelled with anti-ENK (green) and anti-DARPP-32 (red). ENK-negative SPNs from Tor1a+/- slices failed to induce LTD. (B) WB analysis for p-GluA1 (Ser845), GluA1, GluA2, NMDAR2A, NMDAR2B, PSD-95 and α-tubulin in Tor1a+/- and age-matched Tor1a+/+ mice. (C) Histogram showed the quantification of protein levels following normalization on α-tubulin in Tor1a+/- and age-matched Tor1a+/+ mice. All values are mean ± SEM expressed as % of Tor1a+/+ mice. (D) Representative images showed spine morphology of Tor1a+/- and age-matched Tor1a+/+ mice (scale bar: 10 μm). (E) Histogram represented dendritic spine density in Tor1a+/- and Tor1a+/+ SPNs. Tor1a+/- SPNs exhibited an overall decrease of dendritic spine density (P<0.05). (F, G) Histograms showed the quantification of dendritic spine size (F, spine length and head width) and dendritic spine type (G, mushroom, stubby, thin) in Tor1a+/- and age-matched Tor1a+/+ mice. A larger number of mushroom-type spines and a concomitant smaller number of stubby-type spines were found in Tor1a+/- SPNs (both P<0.05). In each group, five mice were used (N=5), and three independent experiments were conducted for each mouse (n=3). P<0.05 was considered to be statistically significant.