Salicylate protects against MPTP-induced impairments in dopaminergic neurotransmission at the striatal and nigral level in mice

Abstract

The analgesic and anti-inflammatory drug sodium salicylate was studied for its potential protective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. C 57BL/6 mice were treated with a single dose of sodium salicylate (50 mg/kg or 100 mg/kg i.p.) or saline immediately before injection of MPTP (30 mg/kg or 40 mg/kg s.c.) or saline. Analysis of striatal dopamine and metabolites as well as immunostaining for tyrosine hydroxylase of nigral sections was performed 7 days after MPTP treatment. MPTP (30 mg/kg) led to a strong decrease in striatal dopamine levels (1.87+/-0.27 ng/mg) compared to saline-treated controls (15.72+/-0.78 ng/mg), which was significantly attenuated by sodium salicylate 50 mg/kg and 100 mg/kg (5.59+/-0.56 ng/mg and 8.64+/-0.89 ng/mg, respectively). Remarkably, the MPTP-induced loss of tyrosine hydroxylase immunoreactivity in nigral cell bodies was nearly completely prevented by the higher dose of sodium salicylate. Furthermore, salicylate demonstrated radical scavenging effects in an in vitro Fenton system indicated by HPLC determination of the dihydroxylated reaction products of salicylate, namely, 2,3- and 2,5-dihydroxybenzoic acid. The protective effects of salicylate against reversible or irreversible impairments in dopaminergic neurotransmission after MPTP treatment may be related to its radical scavenging properties and other mechanisms which need to be clarified.

Non-steroidal anti-inflammatory drugs in Parkinson's disease

“…In addition, SA was found to be neuroprotective, even if not completely, in a higher dosage MPTP mouse model of PD (Ferger et al, 1999). SA acted on both the terminal and cell body area of the nigrostriatal system as might be deduced by the pronounced effect against both MPTP-induced striatal DA depletion and loss of tyrosine hydroxylase (TH) immunoreactive on nigral cell bodies.…”

“…SA acted on both the terminal and cell body area of the nigrostriatal system as might be deduced by the pronounced effect against both MPTP-induced striatal DA depletion and loss of tyrosine hydroxylase (TH) immunoreactive on nigral cell bodies. Ferger and colleagues in their paper pointed out that SA neuroprotective properties are based on its effective hydroxyl radicals scavenger rather than on its COXinhibitory action (Ferger et al, 1999).…”

Acute versus long-term effects of 6-hydroxydopamine on oxidative stress and dopamine depletion in the striatum of mice

“…Radical scavenging activity in mice has already been applied in several studies using an intraperitoneal (i.p.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (Ferger et al, 1999;Lu et al, 2008;Thomas et al, 2000). Generally, the in vivo hydroxyl radical generation in the striatum of mice was analyzed by administrating salicylate i.p.…”

“…Generally, the in vivo hydroxyl radical generation in the striatum of mice was analyzed by administrating salicylate i.p. just before sacrificing the mice or performing microdialysis and determining in real-time the hydroxyl radical generation by striatal perfusion with salicylate (Ferger et al, 1999;Lu et al, 2008;Thomas et al, 2000). In another study, the systemic administration of 3,4-methylendioxymetamphetamine induced free radical formation in mouse striatum was studied with the in vivo salicylate trapping microdialysis (Camarero et al, 2002).…”

Can anti-inflammatory agents protect against Parkinson‘s disease?

“…Besides elucidating a role for neuroinflammation in PD pathogenesis, some studies have also made more specific inquiries into the role of antiinflammatory drugs in neurodegeneration [11][12][13][14][15]. NSAIDs are inhibitors of proinflammatory COX enzymes, and studies have implicated COX in the pathogenesis of PD.…”