Muons penetrate much further than X-rays, they do essentially zero damage, and they are provided for free by the cosmos.
Image credit: Science Source/Digital Globe.
Edited by Anders Bjorklund, Lund University, Lund, Sweden, and approved May 19, 2014 (received for review February 24, 2014)
Article Figures & SI
Figures
- Fig. 1.
Absence of LRRK2 protects from LPS-induced dopaminergic neurodegeneration. LRRK2 WT or KO rats, aged 10–12 wk, were unilaterally injected with either 50 kE.U. (from 10 μg of LPS) or vehicle (PBS) control, and killed 2 wk postinjection. (A) Representative coronal sections of TH-stained SNpc and (B) unbiased stereological counts of TH-positive neurons in the SNpc, with injected side (ipsilateral) counts and noninjected side (contralateral) counts given. Counts expressed as a percentage TH-positive cell loss are shown in Fig. S1 D and E. (C) Stereological counts of CD68-positive myeloid cells in the ipsilateral midbrain sections. Contralateral midbrain sections have negligible CD68 immunoreactivity (<100 cells) and counts are not shown. (D) Representative coronal sections showing CD68 immunoreactivity in the SNpc injected with LPS. (E) Correlation between recruitment of CD68-positive myeloid cells and percentage of surviving TH cells in the SNpc. (F) Perimeter analysis of cells labeled with Iba1 through the midbrain (n = 3 animals per group, >1,000 Iba1 cells analyzed per group). (G) Representative confocal images that span the ipsilateral (LPS-exposed) SNpc. [Scale bar, 0.5 mm for A and D and 100 μm (5 μm for high-magnification insets) for G.] P values are calculated by one-way ANOVA with Tukey’s post hoc test (B, C, D, and F), and linear regression analysis for E (Pearson’s r = −0.75). Error bars represent SEM.
- Fig. 2.
Absence of LRRK2 protects from α-synuclein–induced dopaminergic neurodegeneration. Analysis of 10–12-wk-old LRRK2 WT and KO rats unilaterally injected with 6 × 109 rAAV2 α-synuclein viral particles. (A) Representative DAB images with Nissl counterstain showing human α-synuclein immunoreactivity in neurons of the ipsilateral SNpc 4 wk after viral injection. (B) Representative high-magnification SNpc neurons showing human α-synuclein immunoreactivity and (C) reactivity with a α-synuclein antibody that selective recognizes pathologic inclusions (23). SNpc sections were analyzed for α-synuclein aggregates in Nissl-positive cells at high magnification. (D) Representative coronal sections showing TH immunoreactivity in the SNpc, 4 wk after viral injection. (E) Unbiased stereological analysis of TH-positive neurons in the SNpc with respect to ipsilateral (ipsi, injected) and contralateral (contra, uninjected) sides. Stereological counts of Nissl-positive cells and dopaminergic neurodegeneration, calculated as percentage of remaining neurons, are provided in Fig. S4. (F) Linear regression analysis for SNpc neurodegeneration, determined by stereological counts of TH cells in the SNpc, and the percentage of cells that remain with α-synuclein aggregates. Additional representative images are provided in Fig. S5. (G) Representative coronal sections showing CD68 immunoreactivity in the SNpc and (H) unbiased stereological analysis of CD68 cells, 4 wk postinjection of rAAV2 α-synuclein viral particles. (I) Perimeter analysis of cells labeled with Iba1 through the midbrain (n = 3 animals per group, >1,000 Iba1 cells analyzed per group). (J) Representative confocal sections that span the ipsilateral (α-synuclein transduced) SNpc. CD68 immunoreactivity was never detected on the contralateral side. [Scale bar, 0.5 mm for A, D, and G and 50 μm (and 5 μm for the high-magnification inset) for J.] P values were calculated by one-way ANOVA with Tukey’s post hoc test, and error bars represent SEM.
- Fig. 3.
LRRK2 immunoreactivity in CD68/iNOS-positive cells recruited in response to α-synuclein and LPS-transduced SNpc. (A–D) Representative confocal sections of the unilateral SNpc transduced with rAAV2/1–α-synuclein, into 10–12-wk-old LRRK2 WT rats, killed 4 wk postinjection. LRRK2 (green)/CD68 (red)/iNOS (blue)-positive small amoeboid (spherical) cells (e.g., ∼5 μm) are highlighted with arrowheads. (E–H) In the contralateral side (noninjected), no immunoreactivity could be detected for LRRK2, CD68, and iNOS. (I–L) LRRK2 WT rats, aged 10–12 wk, were unilaterally injected with 50 kE.U. (from 10 μg of LPS) and killed 2 wk postinjection. Confocal analysis of a representative area of the ipsilateral SNpc revealed cells positive for LRRK2, Iba1, CD68, and iNOS. Arrowheads indicate points of reference. (Scale bar, 50 μm for A–H and 20 μm for I–L.)
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LRRK2 deficiency protects from neurodegeneration
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