Effects of Enteric Environmental Modification by Coffee Components on Neurodegeneration in Rotenone-Treated Mice.

Ikuko Miyazaki,Nami Isooka,Ryo Kikuoka,Masato Asanuma,Kouichi Wada,Yoshihisa Kitamura

doi:10.3390/cells8030221

Abstract

Epidemiological studies have shown that coffee consumption decreases the risk of Parkinson’s disease (PD). Caffeic acid (CA) and chlorogenic acid (CGA) are coffee components that have antioxidative properties. Rotenone, a mitochondrial complex I inhibitor, has been used to develop parkinsonian models, because the toxin induces PD-like pathology. Here, we examined the neuroprotective effects of CA and CGA against the rotenone-induced degeneration of central dopaminergic and peripheral enteric neurons. Male C57BL/6J mice were chronically administered rotenone (2.5 mg/kg/day), subcutaneously for four weeks. The animals were orally administered CA or CGA daily for 1 week before rotenone exposure and during the four weeks of rotenone treatment. Administrations of CA or CGA prevented rotenone-induced neurodegeneration of both nigral dopaminergic and intestinal enteric neurons. CA and CGA upregulated the antioxidative molecules, metallothionein (MT)-1,2, in striatal astrocytes of rotenone-injected mice. Primary cultured mesencephalic or enteric cells were pretreated with CA or CGA for 24 h, and then further co-treated with a low dose of rotenone (1–5 nM) for 48 h. The neuroprotective effects and MT upregulation induced by CA and CGA in vivo were reproduced in cultured cells. Our data indicated that intake of coffee components, CA and CGA, enhanced the antioxidative properties of glial cells and prevents rotenone-induced neurodegeneration in both the brain and myenteric plexus.

Highlights

Parkinson’s disease (PD) is a progressive neurodegenerative disease with motor symptoms, such as tremor, akinesia/bradykinesia, rigidity, and postural instability, due to a loss of nigrostriatal dopaminergic neurons, and non-motor symptoms, such as orthostatic hypotension and constipation, caused by peripheral neurodegeneration
We reported that chronic injection with rotenone (50 mg/kg/day) induced neurodegeneration in the substantia nigra pars compacta (SNpc) and intestinal myenteric plexus in mice [27]
The present study demonstrated that Caffeic acid (CA) and chlorogenic acid (CGA) upregulated MT-1,2 in astrocytes and exerted neuroprotective effects against rotenone-induced dopaminergic neurodegeneration in mesencephalic neuronal and astrocyte co-cultures

Summary

Introduction

Parkinson’s disease (PD) is a progressive neurodegenerative disease with motor symptoms, such as tremor, akinesia/bradykinesia, rigidity, and postural instability, due to a loss of nigrostriatal dopaminergic neurons, and non-motor symptoms, such as orthostatic hypotension and constipation, caused by peripheral neurodegeneration. Gastrointestinal dysfunction is a prominent non-motor symptom of PD. Several studies have reported that constipation appears approximately 10 to 20 years prior to the presentation of motor symptoms [1,2,3]. A large-scale prospective study demonstrated that lower bowel movement frequencies predicted the future PD crisis [4]. Reported that PD pathology, Lewy bodies and Lewy neuritis, within the central nervous system (CNS), appeared first in the dorsal motor nucleus of vagus, and extended upward through the brain stem. Cells 2019, 8, 221 to reach the substantia nigra, eventually leading to motor dysfunction [5]. Several reports have demonstrated that PD pathology is detected within the enteric nervous system (ENS) [6,7,8]

Results

Discussion

Conclusion