Effects of repeated systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice on interleukin-1beta and nerve growth factor in the striatum.
Interleukin (IL)-1beta and nerve growth factor (NGF) were measured for the first time in the brain (caudate nucleus and putamen, and frontal cortex) from control mice and mice treated with a parkinsonism-inducing neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), by highly-sensitive sandwich enzyme-linked immunosorbent assays (ELISAs) The concentrations of interleukin (IL)-1beta in the striatal regions were significantly higher in MPTP-treated mice than those in control mice treated with saline (P < 0.005), whereas those in the frontal cortex did not show significant differences between MPTP-treated and control mice. The present results agreed with our previous data on increased IL-1beta in the postmortem striatum from patients with Parkinson's disease (PD). In contrast, the concentrations of nerve growth factor (NGF) in the striatal regions were significantly lower in MPTP-treated mice, down to a 54% level of control mice (P < 0.05), but those in the frontal cortex did not show significant differences between MPTP-treated and control mice. Since NGF may play important roles as neurotrophic factors in the brain, the present results suggest that both the elevation of pro-inflammatory cytokine IL-1beta and the decrease of NGF in the dopaminergic striatal region of MPTP- treated mice may be related to neuronal cell death.
Mogi
M
M
Department of Pharmacology, School of Dentistry, Aichi-Gaknin University, Nagoya, Japan.
Togari
A
A
Ogawa
M
M
Ikeguchi
K
K
Shizuma
N
N
Fan
D
D
Nakano
I
I
Nagatsu
T
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001921:Brain; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004334:Drug Administration Schedule; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000819:agonists*; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors*
D015259:Dopamine Agents; D007375:Interleukin-1; D009414:Nerve Growth Factors; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine