• Berthold Debye, Lena Schmülling, Lepu Zhou, Gabriele Rune, Cordian Beyer, and Sonja Johann.
• Institute of Neuroanatomy, RWTH Aachen University, 52074 Aachen, Wendlingweg 2, Germany.
• Brain Pathol. 2018 Jan 1; 28 (1): 14-27.

AbstractNowadays, amyotrophic lateral sclerosis (ALS) is considered as a multisystem disorder, characterized by a primary degeneration of motor neurons as well as neuropathological changes in non-motor regions. Neurodegeneration in subcortical areas, such as the thalamus, are believed to contribute to cognitive and behavioral abnormalities in ALS patients. In the present study, we investigated neurodegenerative changes including neuronal loss and glia pathology in the anterodorsal thalamic nucleus (AD) of SOD1(G93A) mice, a widely used animal model for ALS. We detected massive dendrite swelling and neuronal loss in SOD1(G93A) animals, which was accompanied by a mild gliosis. Furthermore, misfolded SOD1 protein and autophagy markers were accumulating in the AD. Since innate immunity and activation inflammasomes seem to play a crucial role in ALS, we examined protein expression of Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) and the cytokine interleukin 1 beta (IL1β) in AD glial cells and neurons. NLRP3 and ASC were significantly up-regulated in the AD of SOD1(G93A) mice. Finally, co-localization studies revealed expression of NLRP3, ASC and IL1β in neurons. Our study yielded two main findings: (i) neurodegenerative changes already occur at an early symptomatic stage in the AD and (ii) increased inflammasome expression may contribute to neuronal cell death. In conclusion, neurodegeneration in the anterior thalamus may critically account for cognitive changes in ALS pathology.© 2016 International Society of Neuropathology.

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