1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine‐Induced neurotoxicity in the rat: Characterization and age‐dependent effects

Jarvis, Michael F.; Wagner, George C.

doi:10.1002/syn.890050204

Cited by 31 publications

(2 citation statements)

References 51 publications

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“…This conjecture is consistent with reports of enhanced neurotoxicity and parkinsonism in old animals exposed to DA (Cantuti‐Castelvetri et al. 2003), MPTP (Jarvis and Wagner 1990; Ali et al. 1993), amphetamines (Vasilev et al.…”

Section: Parkinson Diseasesupporting

confidence: 92%

Heme oxygenase‐1 and neurodegeneration: expanding frontiers of engagement

Schipper

Song

Zukor

et al. 2009

Journal of Neurochemistry

255

239

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The heme oxygenases (HOs), responsible for the degradation of heme to biliverdin/bilirubin, free iron and CO, have been heavily implicated in mammalian CNS aging and disease. In normal brain, the expression of HO‐2 is constitutive, abundant and fairly ubiquitous, whereas HO‐1 mRNA and protein are confined to small populations of scattered neurons and neuroglia. In contradistinction to HO‐2, the ho‐1 gene (Hmox1) is exquisitely sensitive to induction by a wide range of pro‐oxidant and other stressors. In Alzheimer disease and mild cognitive impairment, immunoreactive HO‐1 protein is over‐expressed in neurons and astrocytes of the cerebral cortex and hippocampus relative to age‐matched, cognitively intact controls and co‐localizes to senile plaques, neurofibrillary tangles, and corpora amylacea. In Parkinson disease, HO‐1 is markedly over‐expressed in astrocytes of the substantia nigra and decorates Lewy bodies in affected dopaminergic neurons. HMOX1 is also up‐regulated in glial cells surrounding human cerebral infarcts, hemorrhages and contusions, within multiple sclerosis plaques, and in other degenerative and inflammatory human CNS disorders. Heme‐derived free ferrous iron, CO, and biliverdin/bilirubin are biologically active substances that have been shown to either ameliorate or exacerbate neural injury contingent upon specific disease models employed, the intensity and duration of HO‐1 expression and the nature of the prevailing redox microenvironment. In ‘stressed’ astroglia, HO‐1 hyperactivity promotes mitochondrial sequestration of non‐transferrin iron and macroautophagy and may thereby contribute to the pathological iron deposition and bioenergetic failure amply documented in Alzheimer disease, Parkinson disease and other aging‐related neurodegenerative disorders. Glial HO‐1 expression may also impact cell survival and neuroplasticity in these conditions by modulating brain sterol metabolism and proteosomal degradation of neurotoxic protein aggregates.

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Section: Parkinson Diseasesupporting

confidence: 92%

Heme oxygenase‐1 and neurodegeneration: expanding frontiers of engagement

Schipper

Song

Zukor

et al. 2009

Journal of Neurochemistry

255

239

View full text Add to dashboard Cite

show abstract

“…The vulnerability of melanized neurons in idiopathic Parkin son's disease [6] and in l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism [7] sug gests that NM may contribute to the degenerative pro cess. The relationship between increased NM content with age in primates and increased vulnerability to MPTP toxicity [8] called for a careful study of NM pig mentation with aging in the monkey.…”

Section: Introductionmentioning

confidence: 99%

Neuromelanin Accumulation with Age in Catecholaminergic Neurons from <i>Macaca fascicularis </i>Brainstem

Herrero

Hirsch²,

Kästner³

et al. 1993

Dev Neurosci

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Neuromelanin (NM) is an auto-oxidation by-product of catecholamine synthesis which is observed almost exclusively in primates. We have estimated the distribution and the number of NM-positive neurons of the upper brainstem and the degree of their melanization from birth to the onset of senescence in 5 monkeys (Macaca fascicularis) aged 0, 1.5, 3.5, 8 and 13 years. Series of sections taken at 640-µm intervals were examined either unstained to detect unstained NM, stained for NM with Masson silver impregnation or processed by tyrosine hydroxylase (TH) immunohistochemistry to analyze catecholaminergic neurons. The proportion of NM-containing cells among TH-positive neurons varied from one catecholaminergic region to another: low in the hypothalamus and central gray substance (cgs); moderate in the cell group A8, and high in the ventral tegmental area (VTA), locus coeruleus (LC) and substantia nigra (SN). TH-positive neurons were detected in the SN, VTA, catecholaminergic cell group A8, LC, cgs and hypothalamus. At birth, although no unstained NM-positive neurons were detected, Masson-stained cells were observed, though only in the LC. At 1.5 and 3.5 years, Masson-positive neurons were observed despite the absence of visible pigment. At 8 and 13 years, unstained NM was present in Masson-positive neurons. The number of unstained NM-positive neurons and Masson-positive neurons and the amount of NM per neuron increased with age in each subregion studied. Nevertheless, some TH-positive neurons were found to be without NM. The data indicate a differential increased NM content with age in the neurons of midbrain catecholaminergic cell groups. However, its functional significance remains to be determined.

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Alteration of corticotropin‐releasing factor immunoreactivity in MPTP‐treated rats

Huang

Lee

1995

J of Neuroscience Research

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A decrease of corticotropin-releasing factor (CRF) concentration has been reported in patients with Parkinson's disease (PD). The present study further examined the role of CRF in an animal model of parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Results indicated that both subchronic (2 days) and chronic (7 days) MPTP treatments decreased the number of CRF immunoreactive neurons in both the paraventricular nucleus (PVN) of the hypothalamus and the central nuelcus of the amygdala (ACN). This effect lasted for almost a month after withdrawal of chronic MPTP injections. In addition, nomifensine pretreatment protected against MPTP's toxicity on DA neurons, as assessed by tyrosine hydroxylase immunoreactivity in the substantia nigra. However, the same treatment did not prevent the toxicity of MPTP on CRF neurons. Further, no significant difference was notable in the number of CRF immunoreactive neurons between normal young adult and normal middle-aged rats in both the PVN and the ACN. These results suggest that MPTP also produces a neurotoxicity on CRF neurons, and this effect is not secondary to MPTP's effect on DA neurons. Besides, altered CRF neuronal activity is involved in the process of pathological ageing, but not physiological ageing. Further, reduced CRF immunoreactivity in the PVN and ACN may imply alterations of neuroendocrine, autonomic as well as central functions caused by MPTP.

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1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine‐Induced neurotoxicity in the rat: Characterization and age‐dependent effects

Cited by 31 publications

References 51 publications

Heme oxygenase‐1 and neurodegeneration: expanding frontiers of engagement

Heme oxygenase‐1 and neurodegeneration: expanding frontiers of engagement

Neuromelanin Accumulation with Age in Catecholaminergic Neurons from <i>Macaca fascicularis </i>Brainstem

Alteration of corticotropin‐releasing factor immunoreactivity in MPTP‐treated rats

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