Format

Send to

Choose Destination
Neuroscience. 2017 Aug 15;357:37-55. doi: 10.1016/j.neuroscience.2017.05.041. Epub 2017 May 31.

Imaging of glial cell morphology, SOD1 distribution and elemental composition in the brainstem and hippocampus of the ALS hSOD1G93A rat.

Author information

1
Center for Laser Microscopy, Institute for Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Serbia. Electronic address: stefan.stamenkovic@bio.bg.ac.rs.
2
CELLS - ALBA Synchrotron Light Source, Carrer de la Llum 2-26, 08290 Cerdanyola del Valles, Barcelona, Spain.
3
Center for Laser Microscopy, Institute for Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Serbia.
4
Experimental Imaging Unit, Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor and cognitive domains of the CNS. Mutations in the Cu,Zn-superoxide dismutase (SOD1) cause 20% of familial ALS and provoke formation of intracellular aggregates and copper and zinc unbinding, leading to glial activation and neurodegeneration. Therefore, we investigated glial cell morphology, intracellular SOD1 distribution, and elemental composition in the brainstem and hippocampus of the hSOD1G93A transgenic rat model of ALS. Immunostaining for astrocytes, microglia and SOD1 revealed glial proliferation and progressive tissue accumulation of SOD1 in both brain regions of ALS rats starting already at the presymptomatic stage. Glial cell morphology analysis in the brainstem of ALS rats revealed astrocyte activation occurring before disease symptoms onset, followed by activation of microglia. Hippocampal ALS astrocytes exhibited an identical reactive profile, while microglial morphology was unchanged. Additionally, ALS brainstem astrocytes demonstrated progressive SOD1 accumulation in the cell body and processes, while microglial SOD1 levels were reduced and its distribution limited to distal cell processes. In the hippocampus both glial cell types exhibited SOD1 accumulation in the cell body. X-ray fluorescence imaging revealed decreased P and increased Ca, Cl, K, Ni, Cu and Zn in the brainstem, and higher levels of Cl, Ni and Cu, but lower levels of Zn in the hippocampus of symptomatic ALS rats. These results bring new insights into the glial response during disease development and progression in motor as well as in non-motor CNS structures, and indicate disturbed tissue elemental homeostasis as a prominent hallmark of disease pathology.

KEYWORDS:

X-ray fluorescence; amyotrophic lateral sclerosis; brainstem; glia; hSOD1(G93A) rat; hippocampus

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center