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Am J Neurodegener Dis 2012;1(2):122-129

Original Article
Neuroprotection against iron-induced cell death by perineuronal nets - an
in vivo analysis of oxidative stress

Anne Suttkus, Susanne Rohn, Carsten Jäger, Thomas Arendt, Markus Morawski

University of Leipzig, Department for Molecular and Cellular Mechanisms of Neurodegeneration, Paul Flechsig Institute
for Brain Research, Jahnallee 59, 04109 Leipzig, Germany; University of Leipzig, Department for Molecular and Cellular
Mechanisms of Neurodegeneration, Paul Flechsig Institute for Brain Research, Jahnallee 59, 04109 Leipzig, Germany;
Fraunhofer Institute for Cell Therapy and Immunology, Perlickstraße 1, 04103 Leipzig, Germany; University of Leipzig,
Department for Molecular and Cellular Mechanisms of Neurodegeneration, Paul Flechsig Institute for Brain Research,
Jahnallee 59, 04109 Leipzig, Germany; University of Leipzig, Department for Molecular and Cellular Mechanisms of
Neurodegeneration, Paul Flechsig Institute for Brain Research, Jahnallee 59, 04109 Leipzig, Germany.

Received May 29, 2012; accepted June 23, 2012; Epub July 23, 2012; published July 31, 2012

Abstract: Perineuronal nets (PNs) are a specialized form of extracellular matrix, surrounding different types of neurons
and mainly consist of chondroitin sulfate proteoglycans connected to hyaluronan, stabilized by link protein and cross-
linked via tenascin-R. Due to their polyanionic character, caused by the highly charged chondroitin sulfate
glycosaminoglycan and hyaluronan components, PNs might be involved in local ion homeostasis. They are able to
scavenge and bind redox-active ions and thus reduce the local oxidative potential. We investigated whether net-
enwrapped neurons are less vulnerable against iron-induced oxidative processes. Oxidative stress is a key factor in
the development and progression of neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. Iron is
believed to contribute to oxidative stress in Alzheimer brains by catalyzing the generation of free radicals. For examining
potential neuroprotective effects of PNs, mice were microinjected with 0.2µl of a 20mM solution of FeCl3 into the barrel
field while the control group received an equal volume of 0.9% NaCl. Brains were analyzed after time intervals of 24h
and 72h. Neuronal degeneration was visualized using Fluoro-Jade B staining. The presence of PNs was assessed by
Wisteria floribunda agglutinin histochemistry or aggrecan immunocytochemistry. The analysis showed a significant
lower degeneration rate of net-ensheathed neurons in comparison to neurons without PNs. The results suggest a
neuroprotective mechanism associated with the presence of PNs against iron-induced cell death. (AJND1205003)

Keywords: Perineuronal nets, iron, neuroprotection, oxidative stress


Address all correspondence to:
Dr. Thomas Arendt
University of Leipzig
Department for Molecular and Cellular Mechanisms of Neurodegeneration
Paul Flechsig Institute for Brain Research
Jahnallee 59, 04109 Leipzig, Germany.
Tel: 0049 3419725721; Fax: 00493419725729
E-mail: aret@medizin.uni-leipzig.de