Neuroprotective effect of arundic acid, an astrocyte-modulating agent, in mouse brain against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity

Himeda, Toshiki; Kadoguchi, Naoto; Kamiyama, Yuko; Kato, Harubumi; Maegawa, Hitoshi; Araki, Tsutomu

doi:10.1016/j.neuropharm.2005.09.014

Cited by 18 publications

(5 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, we hypothesised that astrocyte activation may underlie the acute increase in T 1 relaxation observed in both the ET-1 and NMDA lesions. Arundic acid (( R )-(–)-2-propyloctanoic acid) has recently been shown to selectively modulate astrocyte activation and to have a potent neuroprotective effect in vivo via astrocyte-dependent mechanisms (Asano et al , 2005; Himeda et al , 2006; Tateishi et al , 2002). In this study, we show that pretreatment with arundic acid significantly reduced the spatial extent of the T 1 change induced by intrastriatal ET-1 injection.…”

Section: Discussionmentioning

confidence: 99%

Acute Astrocyte Activation in Brain Detected by Mri: New Insights into T₁ Hypointensity

Sibson

Lowe

Blamire

et al. 2007

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Increases in the T(1) of brain tissue, which give rise to dark or hypointense areas on T(1)-weighted images using magnetic resonance imaging (MRI), are common to a number of neuropathologies including multiple sclerosis (MS) and ischaemia. However, the biologic significance of T(1) increases remains unclear. Using a multiparametric MRI approach and well-defined experimental models, we have experimentally induced increases in tissue T(1) to determine the underlying cellular basis of such changes. We have shown that a rapid acute increase in T(1) relaxation in the brain occurs in experimental models of both low-flow ischaemia induced by intrastriatal injection of endothelin-1 (ET-1), and excitotoxicity induced by intrastriatal injection of N-methyl-D-aspartate (NMDA). However, there appears to be no consistent correlation between increases in T(1) relaxation and changes in other MRI parameters (apparent diffusion coefficient, T(2) relaxation, or magnetisation transfer ratio of tissue water). Immunohistochemically, one common morphologic feature shared by the ET-1 and NMDA models is acute astrocyte activation, which was detectable within 2 h of intracerebral ET-1 injection. Pretreatment with an inhibitor of astrocyte activation, arundic acid, significantly reduced the spatial extent of the T(1) signal change induced by intrastriatal ET-1 injection. These findings suggest that an increase in T(1) relaxation may identify the acute development of reactive astrocytes within a central nervous system lesion. Early changes in T(1) may, therefore, provide insight into acute and reversible injury processes in neurologic patients, such as those observed before contrast enhancement in MS.

show abstract

Section: Discussionmentioning

confidence: 99%

Acute Astrocyte Activation in Brain Detected by Mri: New Insights into T₁ Hypointensity

Sibson

Lowe

Blamire

et al. 2007

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…In the last years, S100B has been used as a biochemical marker of several CNS disorders, such as traumatic brain injury and Alzheimer's disease (Rothermundt et al, 2003). AA reduces deficits induced by cerebral ischemia and the loss of dopaminergic neurons induced by MPTP in a Parkinson's disease model by suppressing S100B expression (Kato et al, 2003; Matsui et al, 2002; Tateishi et al, 2002) and reducing reactive oxygen species (ROS) levels contributing to neuroprotection against the MPTP‐induced damage in mice brain (Himeda et al, 2006). Interestingly, such protective effects persist even in case of delayed treatment (Oki et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Arundic acid administration protects astrocytes, recovers histological damage and memory deficits induced by neonatal hypoxia ischemia in rats

Mari

Odorcyk

Sanches³

et al. 2019

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

Introduction Perinatal hypoxia‐ischemia (HI) is one of the main causes of mortality and chronic neurological morbidity in infants and children. Astrocytes play a key role in HI progression, becoming reactive in response to the injury, releasing S100 calcium binding protein B (S100B). Since S100B inhibition seems to have neuroprotective effects on central nervous system injury models, here we evaluated the neuroprotective effects of an S100B inhibitor, arundic acid (AA) in a HI model. Methods On the 7th postnatal day, animals were submitted to the combination of common carotid artery occlusion and hypoxic atmosphere (8% O2) for 60 min. Three experiments were performed in order to: (1) define AA dose (0.1, 1 or 10 mg/kg, pre‐hypoxia i.p. injection), (2) test if repeated AA administrations (10 mg/kg at 3 time points: Pre‐hypoxia, 24 h and 48 h after HI) would improve the response and (3) investigate biochemical mechanisms involved in AA protection two days after HI. Results AA at a dose of 10 mg/kg applied before and after hypoxia, was the only treatment protocol that was able to improve HI‐induced memory deficits, to reduce tissue damage, to promote astrocytic survival in the hippocampus and to reduced extracellular release of S100B in the cerebrospinal fluid. Conclusion Overall, AA treatment showed beneficial effects on memory deficits, tissue damage, promoting astrocyte survival likely by reducing S100B release. Protection aided to astrocytes by AA treatment against HI lesion may lead to development of new therapeutic strategies that target these particular cells.

show abstract

“…Arundic acid [(R)-(-)-2-propyloctanoic acid (ONO-2506)] was first discovered as an inhibitor of S100β, a calcium-binding protein produced primarily in astrocytes, ameliorating ischemic brain damage in rats ( Tateishi et al, 2002 ), as well as MPTP-induced PD mice by modulating astrocytic activation ( Kato et al, 2004 ; Himeda et al, 2006 ). Arundic acid exerted protective effects against Mn toxicity by inhibiting Mn-induced downregulation of GLAST/EAAT1 and GLT-1/EAAT2 mRNA and proteins levels in human H4 astrocytes and rat primary astrocytes ( Karki et al, 2018 ).…”

Section: Neurotherapeutics and Their Potential Underlying Mechanisms ...mentioning

confidence: 99%

Mechanisms of manganese-induced neurotoxicity and the pursuit of neurotherapeutic strategies

et al. 2022

View full text Add to dashboard Cite

Chronic exposure to elevated levels of manganese via occupational or environmental settings causes a neurological disorder known as manganism, resembling the symptoms of Parkinson’s disease, such as motor deficits and cognitive impairment. Numerous studies have been conducted to characterize manganese’s neurotoxicity mechanisms in search of effective therapeutics, including natural and synthetic compounds to treat manganese toxicity. Several potential molecular targets of manganese toxicity at the epigenetic and transcriptional levels have been identified recently, which may contribute to develop more precise and effective gene therapies. This review updates findings on manganese-induced neurotoxicity mechanisms on intracellular insults such as oxidative stress, inflammation, excitotoxicity, and mitophagy, as well as transcriptional dysregulations involving Yin Yang 1, RE1-silencing transcription factor, transcription factor EB, and nuclear factor erythroid 2-related factor 2 that could be targets of manganese neurotoxicity therapies. This review also features intracellular proteins such as PTEN-inducible kinase 1, parkin, sirtuins, leucine-rich repeat kinase 2, and α-synuclein, which are associated with manganese-induced dysregulation of autophagy/mitophagy. In addition, newer therapeutic approaches to treat manganese’s neurotoxicity including natural and synthetic compounds modulating excitotoxicity, autophagy, and mitophagy, were reviewed. Taken together, in-depth mechanistic knowledge accompanied by advances in gene and drug delivery strategies will make significant progress in the development of reliable therapeutic interventions against manganese-induced neurotoxicity.

show abstract

Neuroprotective effect of arundic acid, an astrocyte-modulating agent, in mouse brain against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity

Cited by 18 publications

References 60 publications

Acute Astrocyte Activation in Brain Detected by Mri: New Insights into T₁ Hypointensity

Acute Astrocyte Activation in Brain Detected by Mri: New Insights into T₁ Hypointensity

Arundic acid administration protects astrocytes, recovers histological damage and memory deficits induced by neonatal hypoxia ischemia in rats

Mechanisms of manganese-induced neurotoxicity and the pursuit of neurotherapeutic strategies

Contact Info

Product

Resources

About

Neuroprotective effect of arundic acid, an astrocyte-modulating agent, in mouse brain against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity

Cited by 18 publications

References 60 publications

Acute Astrocyte Activation in Brain Detected by Mri: New Insights into T1 Hypointensity

Acute Astrocyte Activation in Brain Detected by Mri: New Insights into T1 Hypointensity

Arundic acid administration protects astrocytes, recovers histological damage and memory deficits induced by neonatal hypoxia ischemia in rats

Mechanisms of manganese-induced neurotoxicity and the pursuit of neurotherapeutic strategies

Contact Info

Product

Resources

About

Acute Astrocyte Activation in Brain Detected by Mri: New Insights into T₁ Hypointensity

Acute Astrocyte Activation in Brain Detected by Mri: New Insights into T₁ Hypointensity