Alteration in Nuclear Factor-KappaB Pathway and Functionality of Estrogen via Receptors Promote Neuroinflammation in Frontal Cortex after 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Treatment.

Soham Mitra,Priyobrata Sinha,Arindam Bhattacharyya,Nabanita Ghosh,Nilkanta Chakrabarti

doi:10.1038/srep13949

Soham Mitra, Priyobrata Sinha + Show 3 more

Open Access

https://doi.org/10.1038/srep13949

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Journal: Scientific Reports	Publication Date: Sep 14, 2015
Citations: 10	License type: CC BY 4.0

Affiliation: University of Calcutta

Abstract

The MPTP mediated neurodegeneration in substantia nigra has been well studied, but not the status of frontal cortex. The novelty of the present study is to explore the sex difference of frontal cortex during MPTP intoxication and to investigate the role of estrogen and its receptors in presence of glial cells in a time chase experiment; to identify which pathway of NF-kappaB exist to proceed the neuroinflammation; to investigate the estrogen binding with its nuclear or cytosolic receptors and whether any direct relation exists between estrogen receptor (ER) -beta and NF-kappaB molecules p65 and RelB. The progression of neurodegeneration occurred with the association of glial cells and functional (via its nuclear and cytosolic receptors) estrogen level. Both the canonical and/or non canonical pathways of NF-kappaB exist in frontal cortex of both the sexes after MPTP treatment. The homodimeric or heterodimeric form of ER-beta binds with NF-kappaB molecules p65 and RelB differently, but the canonical or non canonical pathways of NF-kappaB molecules could not be stopped or may be promoted. The changes in the molecular and cellular pattern in frontal cortex of both sexes during MPTP intoxication depends on the estrogen function via its nuclear or cytosolic estrogen receptors.

Highlights

Identifying environmental factors that predispose to the development of idiopathic PD via oxidative stress, mitochondrial dysfunction, Lewy pathology has proved elusive[6,7]
The results indicated that the FOX3 positive immunoreactivity and the neuronal population decreased significantly compared to the respective controls in frontal cortex of both the sexes during MPTP treatment (Fig. 1A–D) and decreased during the initial and the middle phase but did not recover at the later stage in frontal cortex of both the sexes after MPTP treatment (Fig. 1A–B)
Significant evidences report that the microglial cells play a central role in the degeneration of neurons by secreting pro-inflammatory cytokines in response to MPTP mediated oxidative stress in animal models of PD26,27

Summary

Introduction

Identifying environmental factors that predispose to the development of idiopathic PD via oxidative stress, mitochondrial dysfunction, Lewy pathology has proved elusive[6,7]. The MPTP treated animal model of PD exhibits the neuroinflammation by releasing proinflammatory cytokines from microglial cells/astroglial cells in different time frame during the progression of the disease[10,11]. There are few an evidences present that substantia nigra, but cortical regions are affected by neuroinflammation during the MPTP induced mouse model of PD12,13. There is no clear evidence present, whether estrogen has any significant effect on modulation of NF-κ B during the progression of the disease in cortical regions (mainly in frontal cortex; because motor imbalance and deterioration during the PD related to this region). The present study has been designed to understand the possible crosstalk between estrogen action and NF-κ B during the progression of the neuroinflammation/neurodegeneration in frontal cortex of the MPTP mediated mouse model of PD. The crosstalk has been evaluated with respect to the status of microglial and astroglial cells and in a time dependent manner

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