Systemic LPS Administration Stimulates the Activation of Non-Neuronal Cells in an Experimental Model of Spinal Muscular Atrophy
Eleni Karafoulidou,
Evangelia Kesidou,
Paschalis Theotokis,
Chrystalla Konstantinou,
Maria-Konstantina Nella,
Iliana Michailidou,
Olga Touloumi,
Eleni Polyzoidou,
Ilias Salamotas,
Ofira Einstein,
Athanasios Chatzisotiriou,
Marina-Kleopatra Boziki,
Nikolaos Grigoriadis
Affiliations
Eleni Karafoulidou
Laboratory of Experimental Neurology and Neuroimmunology, 2nd Neurological University Department, AHEPA General Hospital of Thessaloniki, Faculty of Health Science, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Evangelia Kesidou
Laboratory of Experimental Neurology and Neuroimmunology, 2nd Neurological University Department, AHEPA General Hospital of Thessaloniki, Faculty of Health Science, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Paschalis Theotokis
Laboratory of Experimental Neurology and Neuroimmunology, 2nd Neurological University Department, AHEPA General Hospital of Thessaloniki, Faculty of Health Science, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Chrystalla Konstantinou
Laboratory of Experimental Neurology and Neuroimmunology, 2nd Neurological University Department, AHEPA General Hospital of Thessaloniki, Faculty of Health Science, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Maria-Konstantina Nella
Laboratory of Experimental Neurology and Neuroimmunology, 2nd Neurological University Department, AHEPA General Hospital of Thessaloniki, Faculty of Health Science, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Iliana Michailidou
Laboratory of Experimental Neurology and Neuroimmunology, 2nd Neurological University Department, AHEPA General Hospital of Thessaloniki, Faculty of Health Science, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Olga Touloumi
Laboratory of Experimental Neurology and Neuroimmunology, 2nd Neurological University Department, AHEPA General Hospital of Thessaloniki, Faculty of Health Science, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Eleni Polyzoidou
Laboratory of Experimental Neurology and Neuroimmunology, 2nd Neurological University Department, AHEPA General Hospital of Thessaloniki, Faculty of Health Science, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Ilias Salamotas
Laboratory of Experimental Neurology and Neuroimmunology, 2nd Neurological University Department, AHEPA General Hospital of Thessaloniki, Faculty of Health Science, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Ofira Einstein
Department of Physical Therapy, Faculty of Health Sciences, Ariel University, Ariel 40700, Israel
Athanasios Chatzisotiriou
Department of Physiology, Medical School, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Marina-Kleopatra Boziki
Laboratory of Experimental Neurology and Neuroimmunology, 2nd Neurological University Department, AHEPA General Hospital of Thessaloniki, Faculty of Health Science, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Nikolaos Grigoriadis
Laboratory of Experimental Neurology and Neuroimmunology, 2nd Neurological University Department, AHEPA General Hospital of Thessaloniki, Faculty of Health Science, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by deficiency of the survival motor neuron (SMN) protein. Although SMA is a genetic disease, environmental factors contribute to disease progression. Common pathogen components such as lipopolysaccharides (LPS) are considered significant contributors to inflammation and have been associated with muscle atrophy, which is considered a hallmark of SMA. In this study, we used the SMNΔ7 experimental mouse model of SMA to scrutinize the effect of systemic LPS administration, a strong pro-inflammatory stimulus, on disease outcome. Systemic LPS administration promoted a reduction in SMN expression levels in CNS, peripheral lymphoid organs, and skeletal muscles. Moreover, peripheral tissues were more vulnerable to LPS-induced damage compared to CNS tissues. Furthermore, systemic LPS administration resulted in a profound increase in microglia and astrocytes with reactive phenotypes in the CNS of SMNΔ7 mice. In conclusion, we hereby show for the first time that systemic LPS administration, although it may not precipitate alterations in terms of deficits of motor functions in a mouse model of SMA, it may, however, lead to a reduction in the SMN protein expression levels in the skeletal muscles and the CNS, thus promoting synapse damage and glial cells’ reactive phenotype.
