Age-related changes of the nitric oxide system in the rat brain

Siles, Eva; Martı́nez-Lara, Esther; Cañuelo, Ana; Sánchez, Marta; Hernández, Raquel; López-Ramos, Juan Carlos; Moral, Marı́a Luisa Del; Esteban, Francisco J.; Blanco, Santos; Pedrosa, Juan Ángel; Rodrigo, José; Peinado, M.A.

doi:10.1016/s0006-8993(02)03575-8

Cited by 63 publications

(51 citation statements)

References 46 publications

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“…The current literature contains conflicting data concerning the dual role (neuroprotector/neurotoxic) that NO may play in the aging CNS (19). It is mostly believed that NO has neurotoxic effects on neurons, but we found no elevated NOx levels in aged rat brain compared to those of young adults.…”

Section: Discussioncontrasting

confidence: 78%

The effect of intracerebroventricular injection of beta amyloid peptide (1-42) on caspase-3 activity, lipid peroxidation, nitric oxide and nos expression in young adult and aged rat brain

Çetin

Yazıhan²,

Dinçer³

et al. 2012

Turkish Neurosurgery

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AIm: Intracerebroventricular (icv) administration of beta amyloid peptide (Aβ) in rats can be used to model certain aspects of Alzheimer disease (AD).The purpose of this study was to examine the effects of intracerebroventricular Aβ (1-42) peptide injection on caspase-3 activity and expression of nNOS and iNOS, malondialdehyde (MDA), glutathione (GSH) and NOx in the hippocampus, temporal cortex and parietal cortex. mAterIAl and methOds: Groups were defined as 1) young adult control, 2) Aβ (1-42) injected young adult, 3) aged control and 4) Aβ (1-42) injected aged group. Stereotaxic surgery was performed. Aβ (1-42) peptide (5μg/1μl, in each icv) was administered bilateral intracerebroventricularly as a single injection.results: Caspase-3 activity significantly increased in Aβ (1-42) injected aged rats when compared with young adult rats. Aβ (1-42) significantly increased lipid peroxidation in both young adult and aged rats. There was an increase in nNOS expression in the temporal cortex of Aβ (1-42) injected aged rats. COnClusIOn:The most significant increase was seen in hippocampus in caspase-3 levels of the Aged-Aβ 1-42 group. nNOS expression in the hippocampus of aged rats was increased compared to young adult rats. However, nNOX expression in the hippocampus of Aβ (1-42) injected aged rats decreased significantly.KeywOrds: Beta amyloid, Caspase 3 activity, Lipid peroxidation, Nitric oxide, Nitric oxide synthase, Hippocampus, Aging ÖZ AmAÇ: Literatür bulguları, oksidatif stres ve kaspaz aktivitesinin amiolid beta peptid (Aβ)'in meydana getirdiği Alzheimer Hastalığı(AH) nörotoksisitesinde ve yaşlanmada rolü olduğunu göstermektedir. İntraserebroventrikuler (icv) Aβ peptid uygulamaları sıçanlarda AH'nı taklit etmek için kullanılmaktadır. Bu çalışmanın amacı, icv Aβ (1-42) peptid uygulamasının 3-4 aylık genç erişkin ve 22-24 aylık yaşlı sıçanların hipokampus, temporal korteks ve parietal kortekslerinde kaspaz 3 aktivitesi, nNOS ve iNOS ekspresyonu, MDA,GSH ve NO düzeylerine olan etkilerini araştırmaktır. yÖntem ve GereÇler: Gruplar: 1) Genç erişkin kontrol, 2) icv Aβ (1-42) enjekte edilen genç erişkin, 3) Yaşlı kontrol 4) icv Aβ (1-42) enjekte edilen yaşlı grup. Stereotaksik cerrahi uygulanarak her bir serebral ventrikül içerisine 5µg/1µl Aβ(1-42) peptid tek bir kez enjekte edildi. Aβ (1-42) uygulamasından 72 saat sonra sıçanlar dekapite edilerek beyinleri hızla buz üzerinde çıkarıldı.BulGulAr: Aβ(1-42) enjekte edilen yaşlı sıçanlarda genç erişkinlere göre kaspaz 3 aktivitesi anlamlı olarak yüksek bulundu. Aβ(1-42) enjekte edilen hem genç erişkin hem de yaşlı sıçanların temporal ve parietal kortekslerinde MDA düzeyleri anlamlı düzeyde artış gösterdi. nNOS ekspresyonu yaşlı kontrol grubunda genç erişkin kontrol gruba göre hipokampuste yüksek olarak bulundu. sOnuÇ: Yine hipokampuste Aβ(1-42) uygulamasından sonra yaşlı grupta yaşlı kontrol grubuna göre nNOS ekspresyonunda azalma bulundu. Temporal kortekste ise nNOS ekspresyonu Aβ(1-42) uygulamasından sonra yaşlı grupta artmış bulundu. iNOS ekspresyonu ise hiç...

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Section: Discussioncontrasting

confidence: 78%

The effect of intracerebroventricular injection of beta amyloid peptide (1-42) on caspase-3 activity, lipid peroxidation, nitric oxide and nos expression in young adult and aged rat brain

Çetin

Yazıhan²,

Dinçer³

et al. 2012

Turkish Neurosurgery

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“…However, very few systematic studies have addressed the identification of specific protein targets for oxidative modifications in defined protein domains. The main objective of the present study was to characterize the protein targets for nitration in cerebellum, a brain region specifically vulnerable to oxidative damage (Chung et al 2002;Siles et al 2002). The 2DE analysis of soluble cerebellar protein fractions clearly demonstrates an age-dependent accumulation of nitrated proteins, specifically proteins with acidic pI values (Fig.…”

Section: Discussionmentioning

confidence: 86%

“…In fact, cerebellum contains the highest levels of nNOS while showing similar levels of eNOS and iNOS compared with other brain regions such as cereberal cortex and subcortical regions (Siles et al 2002). However, our detection of age-dependent differences in nitration is in contrast to previous 1DE SDS-PAGE studies, in which age-dependent changes in protein nitration were not observed in male Wistar rats (Siles et al 2002). A frequent observation during proteomic studies is that different analytical techniques may show different protein ''16y''15y''14y''13y''12y''11y'' y'' 10 y''9 y'' 7 8y '' 6y''5y''4y''3y''2y patterns (Aulak et al 2005).…”

Section: Discussionmentioning

confidence: 96%

“…The ageassociated loss of specific motor and cognitive functions, paralleled by a region-specific accumulation of oxidative protein modifications emphasizes the critical role of such modifications in the brain (Forster et al 1996). Cerebellum is especially vulnerable to oxidative stress and recent studies indicate an age-dependent increase of total cerebellar 3-NT (Chung et al 2002;Siles et al 2002). The cerebellum plays a key role in memory and motor control, critical functions known to decline as a result of biological aging.…”

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confidence: 99%

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Proteomic analysis of protein nitration in rat cerebellum: effect of biological aging

Gokulrangan

Zaidi

Michaelis

et al. 2006

Journal of Neurochemistry

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3-Nitrotyrosine (3-NT) is a useful biomarker of increasing oxidative stress and protein nitration during biological aging. The proteomic analysis of cerebellar homogenate from Fisher 344/Brown Norway (BN/F1) rats shows an age-dependent increase in protein nitration, monitored by western-blot analysis after two-dimensional gel electrophoresis (2DE), mainly in the acidic region. Analysis of in-gel digests by nanoelectrospray (NSI)-MS/MS resulted in the identification of 16 putatively nitrated proteins. The selective isolation of nitrated proteins using immunoprecipitation, followed by SDS-PAGE and in-gel digest/NSI-MS/MS analysis led to the identification of 22 putatively nitrated proteins, of which 7 were identical to those detected after 2DE. When proteins were separated by solution isoelectrofocusing and analyzed by NSI MS/MS, we obtained MS/MS spectra of 3-NT containing peptides of four proteins -similar to ryanodine receptor 3, low density lipoprotein related receptor 2, similar to nebulin-related anchoring protein isoform C and 2,3 cyclic nucleotide 3-phosphodiesterase. Although the functional consequences of protein nitration for these targets are not yet known, our proteomic experiments serve as a first screen for the more targeted analysis of nitrated proteins from aging cerebellum for functional characterization. Oxidative stress and biological aging contribute to elevated levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), causing reversible as well as irreversible covalent protein modifications (Oliver et al.

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“…If the concentration of this anion is high, NO will lead to lipid peroxidation, otherwise NO will have an antioxidant behavior (Wink et al 1996). In fact, studies in rat cerebellum have showed no variation in the expression of NOS isoforms with aging, confirming that the increase in nitric oxide synthase activity is associated to oxidative status linked to aging process (Blanco et al 2010;Siles et al 2002). Most of the neurodegenerative conditions are associated with a chronic inflammation.…”

Section: Discussionmentioning

confidence: 99%

Age-related changes in nitric oxide activity, cyclic GMP, and TBARS levels in platelets and erythrocytes reflect the oxidative status in central nervous system

Kawamoto

Vasconcelos

Degaspari

et al. 2012

AGE

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Aging is associated with an increased susceptibility to neurodegenerative disorders which has been linked to chronic inflammation. This process generates oxygen-reactive species, ultimately responsible for a process known as oxidative stress, leading to changes in nitric oxide (NO), and cyclic guanosine monophosphate (cyclic GMP) signaling pathway. In previous studies, we showed that human aging was associated with an increase in NO Synthase (NOS) activity, a decrease in basal cyclic GMP levels in human platelets, and an increase in thiobarbituric acid-reactant substances (TBARS) in erythrocytes. The aim of the present work was to evaluate NOS activity, TBARS and cyclic GMP levels in hippocampus and frontal cortex and its correlation to platelets and erythrocytes of 4-, 12-, and 24-month-old rats. The result showed an age-related decrease in cyclic GMP levels which was linked to an increase in NOS activity and TBARS in both central areas as well as in platelets and erythrocytes of rats. The present data confirmed our previous studies performed in human platelets and erythrocytes and validate NOS activity and cyclic GMP in human platelet as well as TBARS in erythrocytes as biomarkers to study agerelated disorders and new anti-aging therapies.

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Age-related changes of the nitric oxide system in the rat brain

Cited by 63 publications

References 46 publications

The effect of intracerebroventricular injection of beta amyloid peptide (1-42) on caspase-3 activity, lipid peroxidation, nitric oxide and nos expression in young adult and aged rat brain

The effect of intracerebroventricular injection of beta amyloid peptide (1-42) on caspase-3 activity, lipid peroxidation, nitric oxide and nos expression in young adult and aged rat brain

Proteomic analysis of protein nitration in rat cerebellum: effect of biological aging

Age-related changes in nitric oxide activity, cyclic GMP, and TBARS levels in platelets and erythrocytes reflect the oxidative status in central nervous system

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