An article published this year in “ALCOHOLISM CLINICAL AND EXPERIMENTAL
RESEARCH” using our FITC-conjugated
annexin-V and cell
impermeant DNA fluorophorepropidium iodide, by our customers from
Department of Molecular and Cellular Pathology of Alcohol, Príncipe Felipe
Research Center, Valencia, Spain, in the analysis of Nalmefene prevents
alcohol-induced neuroinflammation and alcohol drinking preference in adolescent
female mice: role of TLR4. Congrats and Thanks.
Summary:
Background: We previously showed
that, by activating innate immune receptors toll-like 4 (TLR4), adolescent
intermittent ethanol exposure causes neuroinflammation, myelin damage and
behavioral dysfunctions. Recent findings reveal that clinically-used opioid
antagonists naltrexone (NT) and naloxone (NX) inhibit opioid-induced TLR4
signaling, and that NT, NX and nalmefene (NF), the 6-methylene derivative of
NX, are able to reduce alcohol drinking escalation.
Methods: NF (0.1 mg/kg, i.p.)
was injected 1 h prior to ethanol (3 g/kg, i.p.) following intermittent
treatment in female (PND35) adolescent mice. Inflammatory molecules, myelin
proteins and apoptotic markers were assessed in the prefrontal cortex (PFC) and
striatum/nucleus accumbens (STR/NAcc). The effect of NF on alcohol drinking
preference was evaluated in both the WT and TLR4-knock out adolescent mice.
Using astroglial cells, the inhibitory potential of NT, NX and NF on LPS, or
the ethanol-triggered TLR4 response, was compared.
Results: Our findings indicate
that NF prevents the up-regulation of cytokines (IL-1β, IL-17A, TNF-α),
chemokines (MCP-1, MIP-1, KC) and pro-inflammatory mediators (iNOS, COX-2),
along with myelin damage and apoptotic events, in both PFC and STR/NAcc. NF
also abolishes ethanol-induced escalation of alcohol preference/consumption,
but has no effect when administered to TLR4-KO mice. In vitro experiments
indicate that NX and NF inhibit TLR4 activation upon LPS or ethanol
stimulation. Immunofluorescence studies and lipid rafts isolation show that NF is
able to prevent TLR4 translocation to lipid rafts/caveolae in astrocytes.
Conclusions: These results suggest
that NF prevents neuroinflammation and brain damage by blocking the TLR4
response, and also support the role of central pro-inflammatory immune signaling
in the modulation of alcohol consumption/addiction
Reference:
Product link:
FITC Annexin V: http://www.immunostep.com/apoptosis-tools/3731-anxvf-200t.html
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