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Absence of Glia Maturation Factor Protects Dopaminergic Neurons and Improves Motor Behavior in Mouse Model of Parkinsonism

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Abstract

Previously, we have shown that aberrant expression of glia maturation factor (GMF), a proinflammatory protein, is associated with the neuropathological conditions underlying diseases suggesting an important role for GMF in neurodegeneration. In the present study, we demonstrate that absence of GMF suppresses dopaminergic (DA) neuron loss, glial activation, and expression of proinflammatory mediators in the substantia nigra pars compacta (SN) and striatum (STR) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated mice. Dopaminergic neuron numbers in the SN and fiber densities in the STR were reduced in wild type (Wt) mice when compared with GMF-deficient (GMF-KO) mice after MPTP treatment. We compared the motor abnormalities caused by MPTP treatment in Wt and GMF-KO mice as measured by Rota rod and grip strength test. Results show that the deficits in motor coordination and decrease in dopamine and its metabolite content were protected significantly in GMF-KO mice after MPTP treatment when compared with control Wt mice under identical experimental conditions. These findings were further supported by the immunohistochemical analysis that showed reduced glial activation in the SN of MPTP-treated GMF-KO mice. Similarly, in MPTP-treated GMF-KO mice, production of inflammatory tumor necrosis factor alpha, interleukine-1 beta, granulocyte macrophage-colony stimulating factor, and the chemokine (C–C motif) ligand 2 MCP-1 was suppressed, findings consistent with a role for GMF in MPTP neurotoxicity. In conclusion, present investigation provides the first evidence that deficiency of GMF protects the DA neuron loss and reduces the inflammatory load following MPTP administration in mice. Thus depletion of endogenous GMF represents an effective and selective strategy to slow down the MPTP-induced neurodegeneration.

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Acknowledgments

We would like to thank John Nehman and Hayate Javed for excellent technical help. This work was supported by the National Institute of Neurological Disorders and Stroke Grants NS073670 and VA Merit Review Award.

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Authors and Affiliations

  1. Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA

    Mohammad Moshahid Khan, Smita Zaheer, Ramasamy Thangavel, Margi Patel, Duraisamy Kempuraj & Asgar Zaheer

  2. Veterans Affairs Health Care System, Iowa City, IA, 52246, USA

    Duraisamy Kempuraj & Asgar Zaheer

Authors
  1. Mohammad Moshahid Khan
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  2. Smita Zaheer
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  3. Ramasamy Thangavel
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  5. Duraisamy Kempuraj
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  6. Asgar Zaheer
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Correspondence to Asgar Zaheer.

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Khan, M.M., Zaheer, S., Thangavel, R. et al. Absence of Glia Maturation Factor Protects Dopaminergic Neurons and Improves Motor Behavior in Mouse Model of Parkinsonism. Neurochem Res 40, 980–990 (2015). https://doi.org/10.1007/s11064-015-1553-x

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  • DOI: https://doi.org/10.1007/s11064-015-1553-x

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