Abstract:
:P2X7 receptor is a ligand gated ion channel found peripheral macrophages and microglia in the nervous system. The current study investigated the relationship between the activated P2X7 and depression for the first time. Chrysophanol (Chr) was examined for its protective effects against depression targeting P2X7. Chr (20mg/kg, 40mg/kg) and fluoxetine (20mg/kg) were intragastrically treated once daily for 7 consecutive days. Lipopolysaccharide (LPS, 0.5mg/kg) was intraperitoneally injected to develop depression model 30min after drug administration on day 7. Behavioral tests were measured 24h after LPS injection. Interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α levels in serum and hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of P2X7/NF-κB pathway-related proteins were assessed by western blot. The findings showed that Chr remarkably reduced the elevations of IL-6, IL-1β and TNF-α caused by LPS stimulation. The expressions of P2X7, p-IKKα, p-IKKβ, p-IκBα and p-NF-κBp65 were significantly decreased by Chr pretreatment. In addition, immobility time in tail suspension test (TST) and forced swimming test (FST) were reduced by Chr without affecting spontaneous locomotor activity in open filed test (OFT) and the preference for sucrose was also recovered in sucrose preference test (SPT) with Chr preconditioning. Thus, it is reasonable to speculate that Chr might exert antidepressant effect through inhibiting P2X7/NF-κB signaling pathway.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Zhang K,Liu J,You X,Kong P,Song Y,Cao L,Yang S,Wang W,Fu Q,Ma Zdoi
10.1016/j.neulet.2015.12.043subject
Has Abstractpub_date
2016-02-02 00:00:00pages
60-5eissn
0304-3940issn
1872-7972pii
S0304-3940(15)30332-3journal_volume
613pub_type
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