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Published on: January 7, 2014
Delayed treatment with arundic acid reduces the MPTP-induced neurotoxicity in mice
Chie Oki1, Yu Watanabe, Hironori Yokoyama
1Department of Neurobiology and Therapeutics, Graduate School and Faculty of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Japan.
Abstract:
The authors investigated the protective effects of a novel astrocyte-modulating agent, arundic acid, in a 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine (MPTP) mouse model of Parkinson's disease. Male mice received four intraperitoneal (i.p.) injections of MPTP (20 mg/kg) at 2 h intervals. The content of dopamine and its metabolites in the striatum was reduced markedly 7 days after MPTP treatment. The delayed treatment with arundic acid (30 mg/kg, i.p.) administered 3, 4, 5 and 6 days after MPTP treatment did not affect the depletion of dopamine and its metabolites in the striatum. Our immunohistochemical study with anti-tyrosine hydroxylase antibody, anti-neuronal nuclei antibody, anti-glial fibrillary acidic protein antibody, anti-S 100beta antibody and anti-nestin antibody showed that the delayed treatment with arundic acid had a protective effect against MPTP-induced neuronal damage in the striatum and the substantia nigra of mice. Furthermore, this agent ameliorated the severe reductions in number of isolectin reactive microglia in the striatum and the substantia nigra 7 days after MPTP treatment. These results demonstrate that the inhibition of S 100beta synthesis in astrocytes may be the major component of the beneficial effect of arundic acid. Thus, our present findings provide that the therapeutic strategies targeted to astrocytic modulation with arundic acid offers a great potential for restoring the functional capacity of the surviving dopaminergic neurons in individuals affected with Parkinson's disease.
Insights
Arundic acid shows protective effects in a Parkinson
Area of Science:
- Neuroscience
- Pharmacology
- Neurodegenerative Diseases
Background:
- Parkinson's disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons.
- The 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine (MPTP) mouse model is widely used to study Parkinson's disease pathogenesis.
- Arundic acid is a novel astrocyte-modulating agent with potential therapeutic applications.
Purpose of the Study:
- To investigate the neuroprotective effects of delayed arundic acid treatment in an MPTP-induced Parkinson's disease mouse model.
- To explore the underlying mechanisms of arundic acid's action, particularly its effect on astrocytes and microglia.
Main Methods:
- MPTP was administered to male mice to induce Parkinson's-like pathology.
- Arundic acid was administered intraperitoneally at delayed time points after MPTP treatment.
- Immunohistochemistry was used to assess neuronal damage, astrocyte activation (S100beta), and microglial response (isolectin binding).
- Dopamine and its metabolites in the striatum were quantified.
Main Results:
- Delayed arundic acid treatment did not prevent the depletion of dopamine and its metabolites.
- However, arundic acid significantly protected against MPTP-induced neuronal damage in the striatum and substantia nigra.
- Arundic acid ameliorated the MPTP-induced increase in reactive microglia.
- The study suggests that inhibition of S100beta synthesis in astrocytes is a key mechanism for arundic acid's beneficial effects.
Conclusions:
- Arundic acid demonstrates significant neuroprotective effects in the MPTP mouse model of Parkinson's disease, despite not affecting dopamine levels.
- The therapeutic benefits of arundic acid are likely mediated through astrocyte modulation, specifically by inhibiting S100beta synthesis.
- Targeting astrocytic modulation with arundic acid holds promise for developing new therapeutic strategies for Parkinson's disease.
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