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

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.

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

10.21203/rs.3.rs-152500/v1 ◽

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.

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

Clinical Science ◽

10.1042/cs20120560 ◽

2013 ◽

Vol 125 (7) ◽

pp. 329-340 ◽

Cited By ~ 30

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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Oral Feeding with Ethinyl Estradiol Suppresses and Treats Experimental Autoimmune Encephalomyelitis in SJL Mice and Inhibits the Recruitment of Inflammatory Cells into the Central Nervous System

The Journal of Immunology ◽

10.4049/jimmunol.170.3.1548 ◽

2003 ◽

Vol 170 (3) ◽

pp. 1548-1555 ◽

Cited By ~ 80

Author(s):

Sandhya Subramanian ◽

Agata Matejuk ◽

Alex Zamora ◽

Arthur A. Vandenbark ◽

Halina Offner

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Experimental Autoimmune Encephalomyelitis ◽

Ethinyl Estradiol ◽

Inflammatory Cells ◽

Oral Feeding ◽

Autoimmune Encephalomyelitis ◽

The Central Nervous System ◽

Experimental Autoimmune

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/7895293 ◽

2020 ◽

Vol 2020 ◽

pp. 1-19 ◽

Cited By ~ 1

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.

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E- and P-Selectin Are Not Involved in the Recruitment of Inflammatory Cells Across the Blood-Brain Barrier in Experimental Autoimmune Encephalomyelitis

Blood ◽

10.1182/blood.v90.11.4459 ◽

1997 ◽

Vol 90 (11) ◽

pp. 4459-4472 ◽

Cited By ~ 136

Author(s):

Britta Engelhardt ◽

Dietmar Vestweber ◽

Rupert Hallmann ◽

Martina Schulz

Keyword(s):

Experimental Autoimmune Encephalomyelitis ◽

Blood Brain Barrier ◽

Inflammatory Cells ◽

Brain Barrier ◽

Specific Mechanism ◽

Autoimmune Encephalomyelitis ◽

Blood Brain ◽

The Central Nervous System ◽

Gain Access ◽

Experimental Autoimmune

Abstract In experimental autoimmune encephalomyelitis (EAE) inflammatory cells cross the endothelial blood-brain barrier (BBB) and gain access to the central nervous system (CNS). Here we show that E- and P-selectin are not involved in the recruitment of inflammatory cells across the BBB. Neither expression of E- nor P-selectin is induced in BBB-forming endothelium at any time after initiation of EAE. Some of the inflammatory cells present in the CNS during EAE express ligands for E- or P-selectin. However, anti–E- and P-selectin antibodies influence neither immigration of inflammatory cells across the BBB nor the development of EAE. In general, suppression of E- and P-selectin expression on BBB endothelium is dependent on factors derived from the CNS microenvironment, eg, astrocytes. Our results suggest that during EAE suppression of E- and P-selectin expression on the BBB provides a CNS-specific mechanism to reduce leukocyte recruitment into the CNS.

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