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Arundic acid, an astrocyte-modulating agent, protects dopaminergic neurons against MPTP neurotoxicity in mice.
Brain Res. 2004 Dec 24; 1030(1):66-73.BR

Abstract

We examined the neuroprotective effects of a novel astrocyte-modulating agent, arundic acid (ONO-2506), in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Male C57BL/6 mice received four intraperitoneal injections of MPTP (20 mg/kg) at 2 h intervals. Dopamine content in the striatum was reduced to 21% of the normal control after 7 days. Treatment with arundic acid (30 mg/kg, i.p.) administered 1 min, 6 h, 24 h, 48 h, and 72 h after the last MPTP injection prevented the dopamine depletion (52% of the control, p<0.01). In addition, this treatment resulted in behavioral benefits. Behavioral testing showed that MPTP-injected mice exhibited motor deficits in the pole test and catalepsy test after 7 days, but arundic acid prevented the appearance of motor abnormalities in these tests. The MPTP-injected animals exhibited an 87% loss of tyrosine hydroxylase-containing dopaminergic neurons in the substantia nigra after 7 days, but the arundic acid-treated mice showed only a 56% reduction (p<0.01). GFAP-positive reactive astrocytes were accumulated in the striatum and substantia nigra 7 days after the MPTP injection, whereas arundic acid treatment induced an earlier appearance of reactive astrocytes by 3 days. The reactive astrocytes increased the production of S-100 protein, which is thought to promote neuronal damage, but arundic acid suppressed the expression of S-100. Thus, arundic acid protected dopaminergic neurons against MPTP neurotoxicity in mice and ameliorated neurological deficits. The results suggest that the neuroprotection is mediated through the modulation of astrocytic activation, including the inhibition of S-100 protein synthesis.

Authors+Show Affiliations

Department of Neurology, Center for Clinical Medicine and Research, International University of Health and Welfare, 537-3 Iguchi, Nishinasuno, Tochigi 329-2763, Japan. katoh@iuhw.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15567338

Citation

Kato, Hiroyuki, et al. "Arundic Acid, an Astrocyte-modulating Agent, Protects Dopaminergic Neurons Against MPTP Neurotoxicity in Mice." Brain Research, vol. 1030, no. 1, 2004, pp. 66-73.
Kato H, Kurosaki R, Oki C, et al. Arundic acid, an astrocyte-modulating agent, protects dopaminergic neurons against MPTP neurotoxicity in mice. Brain Res. 2004;1030(1):66-73.
Kato, H., Kurosaki, R., Oki, C., & Araki, T. (2004). Arundic acid, an astrocyte-modulating agent, protects dopaminergic neurons against MPTP neurotoxicity in mice. Brain Research, 1030(1), 66-73.
Kato H, et al. Arundic Acid, an Astrocyte-modulating Agent, Protects Dopaminergic Neurons Against MPTP Neurotoxicity in Mice. Brain Res. 2004 Dec 24;1030(1):66-73. PubMed PMID: 15567338.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Arundic acid, an astrocyte-modulating agent, protects dopaminergic neurons against MPTP neurotoxicity in mice. AU - Kato,Hiroyuki, AU - Kurosaki,Rumiko, AU - Oki,Chie, AU - Araki,Tsutomu, PY - 2004/09/27/accepted PY - 2004/11/30/pubmed PY - 2005/2/4/medline PY - 2004/11/30/entrez SP - 66 EP - 73 JF - Brain research JO - Brain Res VL - 1030 IS - 1 N2 - We examined the neuroprotective effects of a novel astrocyte-modulating agent, arundic acid (ONO-2506), in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Male C57BL/6 mice received four intraperitoneal injections of MPTP (20 mg/kg) at 2 h intervals. Dopamine content in the striatum was reduced to 21% of the normal control after 7 days. Treatment with arundic acid (30 mg/kg, i.p.) administered 1 min, 6 h, 24 h, 48 h, and 72 h after the last MPTP injection prevented the dopamine depletion (52% of the control, p<0.01). In addition, this treatment resulted in behavioral benefits. Behavioral testing showed that MPTP-injected mice exhibited motor deficits in the pole test and catalepsy test after 7 days, but arundic acid prevented the appearance of motor abnormalities in these tests. The MPTP-injected animals exhibited an 87% loss of tyrosine hydroxylase-containing dopaminergic neurons in the substantia nigra after 7 days, but the arundic acid-treated mice showed only a 56% reduction (p<0.01). GFAP-positive reactive astrocytes were accumulated in the striatum and substantia nigra 7 days after the MPTP injection, whereas arundic acid treatment induced an earlier appearance of reactive astrocytes by 3 days. The reactive astrocytes increased the production of S-100 protein, which is thought to promote neuronal damage, but arundic acid suppressed the expression of S-100. Thus, arundic acid protected dopaminergic neurons against MPTP neurotoxicity in mice and ameliorated neurological deficits. The results suggest that the neuroprotection is mediated through the modulation of astrocytic activation, including the inhibition of S-100 protein synthesis. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/15567338/Arundic_acid_an_astrocyte_modulating_agent_protects_dopaminergic_neurons_against_MPTP_neurotoxicity_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(04)01606-3 DB - PRIME DP - Unbound Medicine ER -