Mortality, oxidative stress and tau accumulation during ageing in parkin null mice

Rodríguez-Navarro, José Antonio; Casarejos, Marı́a José; Menéndez, Jaime; Solano, Rosa M.; Rodal, Izaskun; Gómez, Ana; Yébenes, Justo Garcı́a de; Mena, María A.

doi:10.1111/j.1471-4159.2007.04762.x

Cited by 77 publications

(67 citation statements)

References 74 publications

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“…Therefore, mutated tau overexpression may impair autophagy affecting microtubular transport of autophagic vesicles. Parkin suppression alters tau aggregation, degradation, and solubility in the brain of aged mice [38]. Parkin is protective for nigro-striatal dopamine neurons in a tau gene transfer neurodegenerative model [52].…”

Section: Discussionmentioning

confidence: 99%

“…Fifty microlitres of the resulting preparation were mixed with DTNB (0.6 mM), NADPH (0.2 mM), and glutathione reductase (1U), and the reaction was monitored in a P96 automatic microtiter reader at 405 nm for 6 minutes. Oxidized glutathione (GSSG) was measured by the method of Griffith [38]. After neutralization with the phosphate buffer, the remaining sample (110 l) was mixed with 2-vinylpyridine (1.1 l) at room temperature for 1 hour, and the reaction was carried out as described above.…”

Section: Glutathione Measurementsmentioning

confidence: 99%

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Natural Cannabinoids Improve Dopamine Neurotransmission and Tau and Amyloid Pathology in a Mouse Model of Tauopathy

Casarejos

Perucho

Gómez

et al. 2013

JAD

Self Cite

103

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Abstract. Cannabinoids are neuroprotective in models of neurodegenerative dementias. Their effects are mostly mediated through CB1 and CB2 receptor-dependent modulation of excitotoxicity, inflammation, oxidative stress, and other processes. We tested the effects of Sativex ® , a mixture of 9 -tetrahydrocannabinol and cannabidiol, acting on both CB1 and CB2 receptors, in parkin-null, human tau overexpressing (PK −/− /Tau VLW ) mice, a model of complex frontotemporal dementia, parkinsonism, and lower motor neuron disease. The animals received Sativex ® , 4.63 mg/kg, ip, daily, for one month, at six months of age, at the onset of the clinical symptoms. We evaluated the effects of Sativex ® on behavior, dopamine neurotransmission, glial activation, redox state, mitochondrial activity, and deposition of abnormal proteins. PK −/− /Tau VLW mice developed the neurological deficits, but those treated with Sativex ® showed less abnormal behaviors related to stress, less auto and hetero-aggression, and less stereotypy. Sativex ® significantly reduced the intraneuronal, MAO-related free radicals produced during dopamine metabolism in the limbic system. Sativex ® also decreased gliosis in cortex and hippocampus, increased the ratio reduced/oxidized glutathione in the limbic system, reduced the levels of iNOS, and increased those of complex IV in the cerebral cortex. With regard to tau and amyloid pathology, Sativex ® reduced the deposition of both in the hippocampus and cerebral cortex of PK −/− /Tau VLW mice and increased autophagy. Sativex ® , even after a short administration in animals with present behavioral and pathological abnormalities, improves the phenotype, the oxidative stress, and the deposition of proteins in PK −/− /Tau VLW mice, a model of complex neurodegenerative disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Glutathione Measurementsmentioning

confidence: 99%

Natural Cannabinoids Improve Dopamine Neurotransmission and Tau and Amyloid Pathology in a Mouse Model of Tauopathy

Casarejos

Perucho

Gómez

et al. 2013

JAD

Self Cite

103

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“…PD and other neurodegenerative disorders affect mature or senile patients and we have observed that neurochemical deficits in PK-KO mice increase with age [20,21,35] (Fig. 5A).…”

Section: Effect Of Np7 On H 2 O 2 Toxicity In Aged Glial Culturesmentioning

confidence: 77%

“…Parkin and DJ-1 lead to impairments of oxidative stress response and PI3K/AKT signaling [38,39]. In young (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) (Fig. 6D).…”

Section: Effects Of Oxidative Stress and Np7 In Signaling Pathwaysmentioning

confidence: 98%

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NP7 protects from cell death induced by oxidative stress in neuronal and glial midbrain cultures from parkin null mice

et al. 2008

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a b s t r a c tParkin mutations produce Parkinson's disease (PD) in humans and nigrostriatal dopamine lesions related to increased free radicals in mice. We examined the effects of NP7, a synthetic, marine derived, free radical scavenger which enters the brain, on H 2 O 2 toxicity in cultured neurons and glia from wild-type (WT) and parkin null mice (PK-KO).NP7, 5-10 lM, prevented the H 2 O 2 induced apoptosis and necrosis of midbrain neuronal and glial cultures from WT and PK-KO mice. NP7 suppressed microglial activation and the H 2 O 2 induced drop-out of dopamine neurons . Furthermore, NP7 prevented the increased phosphorylation of ERK and AKT induced by H 2 O 2 . NP7 may be a promising neuroprotector against oxidative stress in PD.

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Oxidative Stress and Parkinson Disease

Lim

Graham

2011

Oxidative Stress in Vertebrates and Invertebrates

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The cause of Parkinson disease is not known at present, and there are many theories as to why the loss of nerve cells that characterises the condition occurs. In recent years, there has been some interest in role of free-radical damage, particularly the damage caused by highly reactive molecules in Parkinson disease and other conditions. In early stages of Parkinsonism, there appears to be a compensatory increase in the number of dopamine receptors to accommodate the initial loss of dopamine neurons. As the disease progress, the number of dopamine receptors decreases, apparently due to concomitant degeneration of dopamine target sites on striatal neurons. The loss of dopaminergic neurons in Parkinson's disease results in enhanced metabolism of dopamine, augmenting the formation of H 2 O 2 , thus leading to generation of highly neurotoxic radicals (OH • ). It has been supposed that degeneration in Parkinson's disease could be a result from the oxidative stress due to dysregulation of dopamine metabolism with consequent free radical formation, depletion of reduced glutathione, a high level of total iron with reduced level of ferritin and deficiency of mitochondrial complex I.

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Mortality, oxidative stress and tau accumulation during ageing in parkin null mice

Cited by 77 publications

References 74 publications

Natural Cannabinoids Improve Dopamine Neurotransmission and Tau and Amyloid Pathology in a Mouse Model of Tauopathy

Natural Cannabinoids Improve Dopamine Neurotransmission and Tau and Amyloid Pathology in a Mouse Model of Tauopathy

NP7 protects from cell death induced by oxidative stress in neuronal and glial midbrain cultures from parkin null mice

Oxidative Stress and Parkinson Disease

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