A new highly sensitive analytical method for determining gabapentin [1-(aminomethyl) cyclohexaneacetic acid; Neurontin] in serum using gas chromatography/tandem mass spectrometry (GC-MS/MS) was developed. GC-MS/MS was applied to determine the levels of gabapentin in serum samples of mice at 1 and 6 h after oral or intraperitoneal treatment (300 mg/kg). At 1 h, the concentrations of the drug were 4.02 +/- 0.42 and 4.32 +/- 0.28 microg/mL in mice treated orally and intraperitoneally, respectively. At 6 h, drug levels decreased by about 66% in both groups. The method, coupling two stages of mass analysis, could be very useful in identifying the drug in complex mixtures such as blood and urine. Moreover, it is easy and rapid to perform, and sensitive enough to allow the presence of the drug to be determined at very low detection limits. It is a very reliable method for both clinical and experimental monitoring of gabapentin.
Toll-like receptors (TLRs) may have a role in Parkinson's disease (PD). In this study, we aimed at investigating the dopaminergic cell loss and alpha-synuclein (α-SYN) expression in TLR4-deficient mice (TLR4) acutely exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a pharmacological PD model. TLR4 ablation restrained the number of dopaminergic neurons in the substantia nigra (SN), as assessed by tyrosine hydroxylase (TH) protein expression. Intriguingly, TLR4 mice showed massive α-SYN protein accumulation in the midbrain along with high α-SYN mRNA levels in cerebral cortex, striatum, hippocampus, and cerebellum. Contrary to expectations, the high levels of α-SYN do not correlate with greater dopaminergic neuronal loss. The levels of nigral α-SYN protein in TLR4 mice further, but not significantly, increased during MPTP treatment. Contrariwise, MPTP treatment significantly induced the mRNA expression of α-SYN in examined brain regions of WT and TLR4 mice. Protein levels of GATA2, a transcription factor proposed to control α-SYN gene expression, did not change in TLR4 mice at baseline and after MPTP treatment. These findings suggest a role for TLR4 in mediating dopaminergic cell loss and in the constitutive expression of brain α-SYN. However, further exploration is needed in order to establish the actual role of α-SYN in the relative absence of TLR4.
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