Interleukin-4 Protects Dopaminergic NeuronsIn vitrobut Is Dispensable for MPTP-Induced NeurodegenerationIn vivo.
Microglia are involved in physiological as well as neuropathological processes in the central nervous system (CNS). Their functional states are often referred to as M1-like and M2-like activation, and are believed to contribute to neuroinflammation-mediated neurodegeneration or neuroprotection, respectively. Parkinson's disease (PD) is one the most common neurodegenerative disease and is characterized by the progressive loss of midbrain dopaminergic (mDA) neurons in the substantia nigra resulting in bradykinesia, tremor, and rigidity. Interleukin 4 (IL4)-mediated M2-like activation of microglia, which is characterized by upregulation of alternative markers Arginase 1 (Arg1) and Chitinase 3 like 3 (Ym1) has been well studiedin vitrobut the role of endogenous IL4 during CNS pathologiesin vivois not well understood. Interestingly, microglia activation by IL4 has been described to promote neuroprotective and neurorestorative effects, which might be important to slow the progression of neurodegenerative diseases. In the present study, we addressed the role of endogenous and exogenous IL4 during MPP+-induced degeneration of mDA neuronsin vitroand further addressed the impact of IL4-deficiency on neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PDin vivo. Our results clearly demonstrate that exogenous IL4 is important to protect mDA neuronsin vitro, but endogenous IL4 seems to be dispensable for development and maintenance of the nigrostriatal system as well as MPTP-induced loss of TH+neuronsin vivo. These results underline the importance of IL4 in promoting a neuroprotective microglia activation state and strengthen the therapeutic potential of exogenous IL4 for protection of mDA neurons in PD models.
Department of Molecular Embryology, Institute for Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg Freiburg, Germany.
Laura
L
Hühner
Department of Molecular Embryology, Institute for Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg Freiburg, Germany.
Jennifer
J
Rilka
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg Freiburg, Germany.
Ralf
R
Gilsbach
Department of Molecular Embryology, Institute for Anatomy and Cell Biology, Faculty of Medicine, University of FreiburgFreiburg, Germany; Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, IthacaNY, USA.
Xiaolai
X
Zhou
Department of Molecular Embryology, Institute for Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg Freiburg, Germany.
Venissa
V
Machado
Department of Molecular Embryology, Institute for Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg Freiburg, Germany.
Björn
B
Spittau
IL4; MPTP; mDA neuron; microglia; neurodegeneration