Mitochondrial dysfunction, oxidative stress and neurodegeneration

Mancuso, Michelangelo; Coppedè, Fabio; Migliore, Lucia; Siciliano, Gabriele; Murri, Luigi

doi:10.3233/jad-2006-10110

Cited by 181 publications

(158 citation statements)

References 149 publications

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“…Our interest is whether increases in the oxidative strength of the cytosol, as occurs during the overproduction of ROS, modify receptor function. Elevations in cytosolic ROS levels are associated with several diseases (Coyle and Puttfarcken, 1993;Smith et al, 1996;Mattson, 2004;Lin and Beal, 2006;Mancuso et al, 2006;Savitt et al, 2006) and are known to alter the function of several membrane proteins including certain ion channels (Park et al, 1995;Ichinari et al, 1996;Annunziato et al, 2002;Dröge, 2002;Liu and Gutterman, 2002;Tang et al, 2004;Gamper et al, 2006); yet, we have no information whether elevations in cytosolic ROS alter the function of neuronal nAChRs. Given the connection between ROS and disease, if elevations in cytosolic ROS alter the function of neuronal nAChRs, the resulting effects on synaptic transmission could have serious consequences for ROS-related diseases, including associated dysautonomias, particularly if fast nicotinic synapses in the autonomic nervous system are impaired.…”

Section: Introductionmentioning

confidence: 88%

Mitochondrial Reactive Oxygen Species Inactivate Neuronal Nicotinic Acetylcholine Receptors and Induce Long-Term Depression of Fast Nicotinic Synaptic Transmission

Campanucci¹,

Krishnaswamy²,

Cooper³

2008

J. Neurosci.

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Neuronal nicotinic acetylcholine receptors (nAChRs), ligand-gated ion channels implicated in a variety of cognitive, motor, and sensory behaviours, are targeted to compartments rich in mitochondria, particularly postsynaptic domains and presynaptic terminals, exposing these receptors to reactive oxygen species (ROS) generated by oxidative phosphorylation. In addition, these receptors can become exposed to ROS during the progression of certain neurodegenerative diseases. Because ROS are known to modify several membrane proteins, including some types of ion channels, it raises the question of whether elevations in cytosolic ROS alter the function of nAChRs. To address this, we elevated ROS in cultured sympathetic neurons, directly by perfusing neurons intracellularly with ROS, indirectly by blocking the mitochondrial electron transport chain, or noninvasively by transient NGF removal; we then simultaneously measured changes in cytosolic ROS levels and whole-cell ACh-evoked currents. In addition, we elevated cytosolic ROS in postganglionic neurons in intact ganglia and measured changes in nerve-evoked EPSPs. Our experiments indicate that mild elevations in cytosolic ROS, including that produced by transient interruption of NGF signaling, induce a use-dependent, long-lasting rundown of ACh-evoked currents on cultured sympathetic neurons and a long-lasting depression of fast nerve-evoked EPSPs. We show that these effects of cytosolic ROS are specific to nAChRs on neurons and do not cause rundown of ACh-evoked currents on muscle. Our results demonstrate that elevations in cytosolic ROS inactivate neuronal nAChRs in a use-dependent manner and suggest that mild oxidative stress impairs mechanisms mediated by cholinergic nicotinic signaling at neuronal-neuronal synapses.

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Section: Introductionmentioning

confidence: 88%

Mitochondrial Reactive Oxygen Species Inactivate Neuronal Nicotinic Acetylcholine Receptors and Induce Long-Term Depression of Fast Nicotinic Synaptic Transmission

Campanucci¹,

Krishnaswamy²,

Cooper³

2008

J. Neurosci.

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“…In the present study, we find that oxidative DNA dam- It is well documented that oxidative stress contributes to neurodegeneration in the substantia nigra in PD patients, mechanisms of which are very complex [2][3][4][5][6][24][25][26] . In the present study, we established a cell model of PD using MPP + treatment, according to previous descriptions [27] .…”

Section: Discussionmentioning

confidence: 90%

“…Although the primary cause of PD remains unclear, there has been increasing evidence suggesting the involvement of oxidative stress in PD pathogenesis [2][3][4][5][6] . The postmortem studies demonstrate that 8-hydroxy-2'-deoxyguanosine (8-oxodG), a biomarker of oxidative DNA damage, accumulates in substantia nigra neurons [7][8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

“…An intact process of BER involves several steps that rely on many enzymes, among which oxoguanine glycosylase 1 (OGG1) is the most important. OGG1 [1][2][3][4][5][6][7] participates in the base recognition step and limits the rate of BER. It has been shown that OGG1 activity is inversely related to the level of 8-oxodG in brain regions [12] .…”

Section: Introductionmentioning

confidence: 99%

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1-Methyl-4-phenyl-pyridinium time-dependently alters expressions of oxoguanine glycosylase 1 and xeroderma pigmentosum group F protein in PC12 cells

Yang

Sun

2010

Neurosci. Bull.

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Objective To determine if DNA excision repair enzymes oxoguanine glycosylase 1 (OGG1) and xeroderma pigmentosum group F protein (XPF) are involved in the pathogenesis of Parkinson's disease (PD) in a cell model. Methods PC12 cells were treated with 1-Methyl-4-phenylpyridine ion (MPP + ) for various periods of time to induce oxidative DNA damage. MTT assay was used to determine cell viability. Immunocytochemistry with antibody against 8-hydroxy-2'-deoxyguanosine (8-oxodG) was used to evaluate oxidative DNA damage. Immunoblotting was used to detect the protein levels of OGG1 and XPF. Results MPP + treatment (1 mmol/L) for 18 h and 24 h reduced cell viability to 78.6% and 70.3% of the control, respectively, in a time-dependent way. MPP + increased the immunoreactivity of 8-oxodG in the cytoplasm at 3 h and in the nucleus at 24 h of treatment. With the treatment of MPP + , the expression of OGG1 was significantly increased at 1 h, reaching a peak at 3 h, and then it was decreased at 24 h, as compared to that with vehicle treatment. The same effect was exerted on XPF level, except that the XPF level reached a peak at 18 h of MPP + treatment. Moreover, the maximally-increased protein level of OGG1 by MPP + was approximately 2-fold higher than that of XPF. Conclusion MPP + treatment could timedependently induce increases in OGG1 and XPF expressions in PC12 cells. Also, this study indicates that the base and nucleotide excision repair pathways may be compensatorily activated in the early stage of pathogenesis in the cells after MPP + treatment.

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“…Milner (1959) in a clinical study found that chronic alcoholic patients and patients with hippocampal damage are similar performers in short term memory tasks [2]. Studies have shown the presence of potential neuroprotective plant with flavonoid and coumarin compounds of FP that plays an important role against stress induced neuronal damage [3,4]. The present scientific article is the histomorphometric study of Fructus Psoralea on ethanol induced neurodegeneration of hippocampus in wistar albino rat.…”

Section: Introductionmentioning

confidence: 99%

Histomorphometric Study of Fructus Psoralea on Ethanol Induced Neurodegeneration of Hippocampus in Rat

Ramar¹

2013

JCDR

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Aim:The histomophometric study of Fructus Psoralea (FP) on ethanol induced neurodegeneration of hippocampus was investigated in a rat by using micrometry. Material and Methods:The study was conducted on thirty healthy female adult wistar albino rats with regular 4-day estrus cycles. The experiment was carried out for a period of 2-4 months. The rats were divided into-SHAM operated control group (Group I) and experimental groups -overiectomised vehicle control rat (Group II), OVX and orally treated with FP(Group III) OVX and induced with ethanol (Group IV), OVX rats induced with ethnaol and orally treated with FP (Group V). ANOVA tool was used to test the mean positive behavioural activity of all the groups. The diameter, packing density and the total number of neurons were calculated from toluidine blue stained histological section by using micrometry. The statistical package SPSS (17.0 VERSION) was used. Statistical significance was defined as p < 0.05. Data was expressed as mean ± SEM. Discussion:In animal studies, ethanol was found to significantly inhibit neuronal activity in the CA1 and CA3 pyramidal cell layers of the hippocampus. FP increase the number of cholinergic neurons in the basal forebrain which in turn leads to increased function of hippocampus, a structure heavily implicated in behavioural activity and memory consolidation. Conclusion:People with extensive hippocampal damage may experience amnesia, learning and memory disabilities. Hence the herb FP may be used as an adjuvant to treat the above neurological disorders.

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Mitochondrial dysfunction, oxidative stress and neurodegeneration

Cited by 181 publications

References 149 publications

Mitochondrial Reactive Oxygen Species Inactivate Neuronal Nicotinic Acetylcholine Receptors and Induce Long-Term Depression of Fast Nicotinic Synaptic Transmission

Mitochondrial Reactive Oxygen Species Inactivate Neuronal Nicotinic Acetylcholine Receptors and Induce Long-Term Depression of Fast Nicotinic Synaptic Transmission

1-Methyl-4-phenyl-pyridinium time-dependently alters expressions of oxoguanine glycosylase 1 and xeroderma pigmentosum group F protein in PC12 cells

Histomorphometric Study of Fructus Psoralea on Ethanol Induced Neurodegeneration of Hippocampus in Rat

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