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Front. Cell. Neurosci. | doi: 10.3389/fncel.2018.00451

Unexpected exacerbation of neuroinflammatory response after a combined therapy in old Parkinsonian mice

 Ana Luisa Gil Martínez1,  Lorena Cuenca1, Cristina Estrada1, Consuelo Sánchez rodrigo1, Emiliano Fernández Villalba1 and  Maria Trinidad Herrero1*
  • 1Universidad de Murcia, Spain

The design of therapeutic strategies that focus on the repositioning of anti-inflammatory and antioxidant drugs are a great bet to slow down the progression of neurodegenerative disorders. Despite the fact that Parkinson’s disease (PD) is an age-related pathology, almost all experimental studies are carried out in young animals. Here, we evaluated the possible neuroprotective effect of the combination of the antioxidant N-acetylcysteine (NAC) and the anti-inflammatory HA-1077 in aged 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice (C57BL/6 mice, 20 months old), whose individual treatment has been shown to have neuroprotective effects in this Parkinsonism model. Interestingly, NAC+HA-1077-based treatment produced a significant increase in dopaminergic neuronal death accompanied by an increase in microglial and astroglial activation in the Substantia Nigra pars compacta (SNpc) and striatum of old-Parkinsonian mice compared to their control group. Astroglial response was also explored by co-immunostaining for GFAP and S100b together with p-JNK and it was found to be particularly exacerbated in the MPTP+NAC+HA-1077 group. The unexpected toxic effects found in the combined use of NAC and HA-1077 in old-Parkinsonian mice highlight the importance of taking into account that in elderly Parkinsonian patients the combination of some drugs (most of them used for other different age-related alterations) can have side effects that may result in the exacerbation of the neurodegenerative process.

Keywords: Aging, Drug-repositioning, glia, Oxidative Stress, parkinsonism

Received: 25 Sep 2018; Accepted: 08 Nov 2018.

Edited by:

Xiaobo Mao, School of Medicine, Johns Hopkins University, United States

Reviewed by:

Jianmin Zhang, Chinese Academy of Medical Sciences, China
Jooho Shin, School of Medicine, Sungkyunkwan University, South Korea  

Copyright: © 2018 Gil Martínez, Cuenca, Estrada, Sánchez rodrigo, Fernández Villalba and Herrero. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Maria Trinidad Herrero, Universidad de Murcia, Murcia, 30003, Murcia, Spain, herreromt@gmail.com