Neuroprotective effect of benzylideneacetophenone derivative on the MPTP model of neurodegeneration in mice

Abstract

In this study, we investigated the neuroprotective effect of a benzylideneacetophenone derivative, JC3, in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD). C57BL/6 mice were treated with MPTP (30 mg/kg, i.p.) for 5 consecutive days. JC3 (10 mg/kg, i.p.) treatment was initiated 2 h after the first administration of MPTP and then at 24-h intervals for 3 consecutive days. The mice were sacrificed for analyses 7 days after the last MPTP injection. Immunohistochemistry and Western blot were used to determine the expression levels of tyrosine hydroxylase (TH), dopamine transporter (DAT), OX-42 (a marker of microglial activation), and glial fibrillary acid protein (GFAP, a marker of astrocyte activation) in the substantia nigra (SN) and striatum (ST). The results of these experiments demonstrated that JC3 restored the decreased TH-immunoreactivity (IR) and DAT and JC3 attenuated the increase in OX-42, GFAP, and COX-2 on the SN and ST on day 7 post-MPTP injection. These results suggest that JC3 can be a neuroprotective agent in an MPTP-induced model of PD.

Treadmill exercise ameliorates dopaminergic neuronal loss through suppressing microglial activation in Parkinson's disease mice

“…CD11b is a surface marker located on the plasma membrane of microglia cells, the expression of which is increased during microglial activation (Singh et al, 2011). Suppressed CD11b expression exerted neuroprotective effects in the MPTP-induced neurodegeneration mouse model (Kang et al, 2008). Microglial activation is evidenced by enhanced CD11b immunostaining in the substantia nigra of mice (Yadav et al, 2012).…”

“…Among them, inducible nitric oxide synthase (iNOS) catalyzes the oxidative deamination of Activated microglia readily undergo dramatic changes in morphology and surface expression of molecules such as major histocompatibility complex, which is recognized by the antibody to CD11b. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration resulted in a significant increase in CD11b expression in the striatum and substantia nigra (Kang et al, 2008). CD11b is the surface marker located on the plasma membrane of microglia, the expression of which is increased during microglial activation (Singh et al, 2011).…”

Benzylideneacetophenone derivatives attenuate IFN-γ-induced IP-10/CXCL10 production in orbital fibroblasts of patients with thyroid-associated ophthalmopathy through STAT-1 inhibition

“…These include modulation of LPS-induced NO generation, iNOS gene expression, proinflammatory cytokine expression and reactive oxygen species generation. 34 In orbital fibroblasts from patients with TAO, JC3 inhibited IFN-γ-induced IP-10/CXCL10 expression, primarily through suppression of STAT-1 pathways (Figure 6a). Expression of the IP-10/CXCL10 gene is regulated by several putative transcription factors, including NF-κB and STAT-1 (the activation of which is induced by IFN-γ).…”

“…Although we could not include in vivo experiments in this study, one author of this study (S. Oh) previously showed the anti-inflammatory and neuroprotective effects of JC3 in vivo using a mouse model of Parkinson's disease. 33, 34 In those studies, 10–30 μ M JC3 was effective in in vitro experiments, whereas mice tolerated JC3 at 10 mg kg −1 , administered at 24-h intervals for three consecutive days, or a single administration of JC3 (30 mg kg −1 ). 33, 34 In our present study, we showed that the IFN-γ-induced increases in IP-10/CXCL10 expression were reduced using 10 μ M JC3 monomer, 1 μ M dimer and 0.1 μ M trimer, those are comparable to doses used previously.…”

“…33, 34 In those studies, 10–30 μ M JC3 was effective in in vitro experiments, whereas mice tolerated JC3 at 10 mg kg −1 , administered at 24-h intervals for three consecutive days, or a single administration of JC3 (30 mg kg −1 ). 33, 34 In our present study, we showed that the IFN-γ-induced increases in IP-10/CXCL10 expression were reduced using 10 μ M JC3 monomer, 1 μ M dimer and 0.1 μ M trimer, those are comparable to doses used previously. 33, 34 However, to evaluate the anti-inflammatory activity of JC3 monomer or polymer in vivo , further research and preclinical studies are necessary to ensure the safety of JC3 treatment, and to determine the optimum dose of JC3 for the treatment of TAO.…”