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

Wei, L;Xue, Z;Lan, B;Yuan, S;Li, Y;Guo, C;Zhang, R;Ding, R;Shen, H;

Background
Multiple sclerosis (MS) is a chronic disease in the central nervous system (CNS), characterized by
inammatory 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-inammation and neuroprotection. However, the effects of Arctigenin on neural
activity attacked by inammation 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.
Results
Here we found added hyperactive cells, calcium inux, network connectivity and synchronization, mainly
at preclinical stage of EAE model. Besides, more silent cells and decreased calcium inux 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 inux and network activity at preclinical stage, but also restored neuronal activity and
communication at remission stage. In addition, we conrmed that the frequency of AMPA receptor-sEPSC
was also increased at preclinical stage and can be blunted by Arctigenin.
Conclusions
Our ndings suggest that excitotoxicity resulted from calcium inux 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 p