scholarly journals Arctigenin Exerts Neuroprotective Effect By Ameliorating Cortical Activities in Experimental Autoimmune Encephalomyelitis in Vivo

2021 ◽  
Author(s):  
Liangpeng Wei ◽  
Zhenyi Xue ◽  
Baihui Lan ◽  
Shiyang Yuan ◽  
Yuanyuan Li ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Ampa Receptor ◽  
Calcium Influx ◽  
Neuroprotective Effect ◽  
Network Activity ◽  
Autoimmune Encephalomyelitis ◽  
Preclinical Stage ◽  
Eae Model ◽  
Experimental Autoimmune

Abstract Background Multiple sclerosis (MS) is a chronic disease in the central nervous system (CNS), characterized by inflammatory cells invade into the brain and the spinal cord. Among a bulk of different MS models, the rodent model of experimental autoimmune encephalomyelitis (EAE) is the most widely used and best understood. Arctigenin, a botanical extract from Arctium lappa, is reported to exhibit pharmacological properties including anti-inflammation and neuroprotection. However, the effects of Arctigenin on neural activity attacked by inflammation in MS are still unclear.Methods Female C57BL/6 mice were expressed by an ultra-sensitive protein calcium sensor GCamp6f in somatosensory cortex neurons through stereotaxic virus injection. Then we induced EAE model in mice with myelin oligodendrocyte glycoprotein (MOG) peptide (35-55) and used two-photon calcium imaging to chronically observe cortical activity in vivo throughout the disease progression. Besides, we performed whole-cell electrophysiological recording to determine the frequency of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated spontaneous excitatory postsynaptic current (sEPSC) in cortical brain slices of preclinical EAE mice.ResultsHere we found added hyperactive cells, calcium influx, network connectivity and synchronization, mainly at preclinical stage of EAE model. Besides, more silent cells and decreased calcium influx and reduced network synchronization accompanied by a compensatory rise in functional connectivity were found at the remission stage. Arctigenin treatment not only restricted inordinate individually neural spiking, calcium influx and network activity at preclinical stage, but also restored neuronal activity and communication at remission stage. In addition, we confirmed that the frequency of AMPA receptor-sEPSC was also increased at preclinical stage and can be blunted by Arctigenin. Conclusions Our findings suggest that excitotoxicity resulted from calcium influx is involved in EAE at preclinical stage. Moreover, Arctigenin exerts neuroprotective effect by limiting hyperactivity at preclinical stage and ameliorates EAE symptoms, indicating Arctigenin could be a potential therapeutic drug for neuroprotection in MS-related neuropsychological disorders.

scholarly journals Arctigenin Exerts Neuroprotective Effect by Ameliorating Cortical Activities in Experimental Autoimmune Encephalomyelitis In Vivo

2021 ◽  
Vol 12 ◽  
Author(s):  
Liangpeng Wei ◽  
Zhenyi Xue ◽  
Baihui Lan ◽  
Shiyang Yuan ◽  
Yuanyuan Li ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Calcium Influx ◽  
Neuroprotective Effect ◽  
Inflammatory Cells ◽  
Network Activity ◽  
Therapeutic Drug ◽  
Autoimmune Encephalomyelitis ◽  
Preclinical Stage ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic disease in the central nervous system (CNS), characterized by inflammatory cells that invade into the brain and the spinal cord. Among a bulk of different MS models, the most widely used and best understood rodent model is experimental autoimmune encephalomyelitis (EAE). Arctigenin, a botanical extract from Arctium lappa, is reported to exhibit pharmacological properties, including anti-inflammation and neuroprotection. However, the effects of arctigenin on neural activity attacked by inflammation in MS are still unclear. Here, we use two-photon calcium imaging to observe the activity of somatosensory cortex neurons in awake EAE mice in vivo and found added hyperactive cells, calcium influx, network connectivity, and synchronization, mainly at preclinical stage of EAE model. Besides, more silent cells and decreased calcium influx and reduced network synchronization accompanied by a compensatory rise in functional connectivity are found at the remission stage. Arctigenin treatment not only restricts inordinate individually neural spiking, calcium influx, and network activity at preclinical stage but also restores neuronal activity and communication at remission stage. In addition, we confirm that the frequency of AMPA receptor-mediated spontaneous excitatory postsynaptic current (sEPSC) is also increased at preclinical stage and can be blunted by arctigenin. These findings suggest that excitotoxicity characterized by calcium influx is involved in EAE at preclinical stage. What is more, arctigenin exerts neuroprotective effect by limiting hyperactivity at preclinical stage and ameliorates EAE symptoms, indicating that arctigenin could be a potential therapeutic drug for neuroprotection in MS-related neuropsychological disorders.

scholarly journals Hormones in experimental autoimmune encephalomyelitis (EAE) animal models

2021 ◽  
Vol 12 (1) ◽  
pp. 164-189
Author(s):  
Majid Ghareghani ◽  
Amir Ghanbari ◽  
Ali Eid ◽  
Abdullah Shaito ◽  
Wael Mohamed ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Demyelinating Disease ◽  
Endocrine System ◽  
Laboratory Animals ◽  
Autoimmune Encephalomyelitis ◽  
Eae Model ◽  
Experimental Autoimmune

Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) in which activated immune cells attack the CNS and cause inflammation and demyelination. While the etiology of MS is still largely unknown, the interaction between hormones and the immune system plays a role in disease progression, but the mechanisms by which this occurs are incompletely understood. Several in vitro and in vivo experimental, but also clinical studies, have addressed the possible role of the endocrine system in susceptibility and severity of autoimmune diseases. Although there are several demyelinating models, experimental autoimmune encephalomyelitis (EAE) is the oldest and most commonly used model for MS in laboratory animals which enables researchers to translate their findings from EAE into human. Evidences imply that there is great heterogeneity in the susceptibility to the induction, the method of induction, and the response to various immunological or pharmacological interventions, which led to conflicting results on the role of specific hormones in the EAE model. In this review, we address the role of endocrine system in EAE model to provide a comprehensive view and a better understanding of the interactions between the endocrine and the immune systems in various models of EAE, to open up a ground for further detailed studies in this field by considering and comparing the results and models used in previous studies.

scholarly journals Bu-Shen-Yi-Sui Capsule, an Herbal Medicine Formula, Promotes Remyelination by Modulating the Molecular Signals via Exosomes in Mice with Experimental Autoimmune Encephalomyelitis

2020 ◽  
Vol 2020 ◽  
pp. 1-19 ◽  
Author(s):  
Pei-Yuan Zhao ◽  
Jing Ji ◽  
Xi-Hong Liu ◽  
Hui Zhao ◽  
Bin Xue ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Neuroprotective Effect ◽  
The Body ◽  
Biological Information ◽  
Neurological Injury ◽  
Autoimmune Encephalomyelitis ◽  
Molecular Signals ◽  
Serum Exosomes ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a common inflammatory demyelinating disorder of the central nervous system. Bu-shen-yi-sui capsule (BSYSC) could significantly reduce the relapse rate, prevent the progression of MS, and enhance remyelination following neurological injury in experimental autoimmune encephalomyelitis (EAE), an established model of MS; however, the mechanism underlying the effect of BSYSC on remyelination has not been well elucidated. This study showed that exosomes carrying biological information are involved in the pathological process of MS and that modified exosomes can promote remyelination by modulating related proteins and microRNAs (miRs). Here, the mechanism by which BSYSC promoted remyelination via exosome-mediated molecular signals was investigated in EAE mice and oligodendrocyte progenitor cells (OPCs) in vitro. The results showed that BSYSC treatment significantly improved the body weight and clinical scores of EAE mice, alleviated inflammatory infiltration and nerve fiber injury, protected the ultrastructural integrity of the myelin sheath, and significantly increased the expression of myelin basic protein (MBP) in EAE mice. In an in vitro OPC study, BSYSC-containing serum, especially 20% BSYSC, promoted the proliferation and migration of OPCs and induced OPCs to differentiate into mature oligodendrocytes that expressed MBP. Furthermore, BSYSC treatment regulated the expression of neuropilin- (NRP-) 1 and GTX, downregulated the expression of miR-16, let-7, miR-15, miR-98, miR-486, and miR-182, and upregulated the level of miR-146 in serum exosomes of EAE mice. In conclusion, these results suggested that BSYSC has a neuroprotective effect and facilitates remyelination and that the mechanism underlying the effect of BSYSC on remyelination probably involves regulation of the NRP-1 and GTX proteins and miRs in serum exosomes, which drive promyelination.

In vivo molecular imaging of adhesion molecules in experimental autoimmune encephalomyelitis (EAE)

2005 ◽  
Vol 25 (3) ◽  
pp. 199-205 ◽  
Author(s):  
Ralf A. Linker ◽  
Michael Reinhardt ◽  
Martin Bendszus ◽  
Gesa Ladewig ◽  
Andreas Briel ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Adhesion Molecules ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

α-Lipoic acid enhances endogenous peroxisome-proliferator-activated receptor-γ to ameliorate experimental autoimmune encephalomyelitis in mice

2013 ◽  
Vol 125 (7) ◽  
pp. 329-340 ◽  
Author(s):  
Kai-Chen Wang ◽  
Ching-Piao Tsai ◽  
Chao-Lin Lee ◽  
Shao-Yuan Chen ◽  
Gu-Jiun Lin ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Lipoic Acid ◽  
Inflammatory Cells ◽  
Treg Cells ◽  
Peroxisome Proliferator ◽  
Autoimmune Encephalomyelitis ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Experimental Autoimmune

ALA (α-lipoic acid) is a natural, endogenous antioxidant that acts as a PPAR-γ (peroxisome-proliferator-activated receptor-γ) agonist to counteract oxidative stress. Thus far, the antioxidative and immunomodulatory effects of ALA on EAE (experimental autoimmune encephalomyelitis) are not well understood. In this study, we found that ALA restricts the infiltration of inflammatory cells into the CNS (central nervous system) in MOG (myelin oligodendrocyte glycoprotein)-EAE mice, thus reducing the disease severity. In addition, we revealed that ALA significantly suppresses the number and percentage of encephalitogenic Th1 and Th17 cells and increases splenic Treg-cells (regulatory T-cells). Strikingly, we further demonstrated that ALA induces endogenous PPAR-γ centrally and peripherally but has no effect on HO-1 (haem oxygenase 1). Together, these data suggest that ALA can up-regulate endogenous systemic and central PPAR-γ and enhance systemic Treg-cells to inhibit the inflammatory response and ameliorate MOG-EAE. In conclusion, our data provide the first evidence that ALA can augment the production of PPAR-γ in vivo and modulate adaptive immunity both centrally and peripherally in EAE and may reveal further antioxidative and immunomodulatory mechanisms for the application of ALA in human MS (multiple sclerosis).

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