Changes in oxidative stress parameters and neurodegeneration markers in the brain of the senescence-accelerated mice SAMP-8

Sureda, Francesc X.; Gutiérrez‐Cuesta, Javier; Romeu, Marta; Mulero, Miquel; Canudas, Anna Maria; Camins, Antoni; Mallol, Jordi; Pallàs, Mercè

doi:10.1016/j.exger.2006.01.015

Cited by 78 publications

(69 citation statements)

References 42 publications

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“…Recently, several authors reported an age-dependent pattern of glial tau aggregation in both human and baboon brains (Schultz et al, 2000;Yang et al, 2005b). Previous studies have shown that hyperphosphorylation of tau occurs in the brain of SAMP8 mice at 5 months of age (Canudas et al, 2005;Sureda et al, 2006). Consistent with these data, the present study has demonstrated increased tau phosphorylation at Ser 199 and Ser 396 in SAMP8 astrocyte cultures obtained from neonate brain, as compared with those of SAMR1 mice.…”

Section: Discussionsupporting

confidence: 90%

“…Thus, changes in astrocyte function may play a key role in determining neuronal survival in the aged SAMP8 brain. Indeed, increases in GFAP expression and PK-11195 binding activity (a marker of gliosis), together with neurodegeneration, have been reported in the hippocampus and cerebral cortex of SAMP8 mice (Nomura et al, 1996;Wu et al, 2005;Sureda et al, 2006). Altered astrocytic function may contribute not only to brain neurodegeneration, but also to the premature learning and memory deficits observed in this murine model of early aging.…”

Section: Discussionmentioning

confidence: 87%

“…In addition, chronic administration of antioxidants, such as melatonin, α -lipoic acid, N-acetylcysteine and acetyl-L-carnitine, to SAMP8 mice not only reduced oxidative damage to neural lipids and proteins, but also lessened cognitive deficits (Okatani et al ., 2002;Yasui et al ., 2002;Farr et al ., 2003;Poon et al ., 2005). Decreases in superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase activities, as well as increases in acyl-CoA oxidase, which have been detected early in SAMP8 mice (1-12 months) compared with age-matched SAMR1 controls (Sato et al ., 1996b;Kurokawa et al ., 2001;Okatani et al ., 2002;Alvarez-García et al ., 2006;Sureda et al ., 2006), may cause elevated generation of ROS. On the other hand, ROS generated by mitochondria or from other cell sites not only cause damage to mitochondrial components and DNA, but also trigger degradative processes that contribute to the aging process (Cadenas & Davies, 2000;Manczak et al ., 2005).…”

Section: Introductionmentioning

confidence: 99%

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Dysfunction of astrocytes in senescence‐accelerated mice SAMP8 reduces their neuroprotective capacity

et al. 2008

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SummaryEarly onset increases in oxidative stress and tau pathology are present in the brain of senescence-accelerated mice prone (SAMP8). Astrocytes play an essential role, both in determining the brain's susceptibility to oxidative damage and in protecting neurons. In this study, we examine changes in tau phosphorylation, oxidative stress and glutamate uptake in primary cultures of cortical astrocytes from neonatal SAMP8 mice and senescenceaccelerated-resistant mice (SAMR1). We demonstrated an enhancement of abnormally phosphorylated tau in Ser 199 and Ser 396 in SAMP8 astrocytes compared with that of SAMR1 control mice. Gsk3β β β β and Cdk5 kinase activity, which regulate tau phosphorylation, was also increased in SAMP8 astrocytes. Inhibition of Gsk3β β β β by lithium or Cdk5 by roscovitine reduced tau phosphorylation at Ser 396 .Moreover, we detected an increase in radical superoxide generation, which may be responsible for the corresponding increase in lipoperoxidation and protein oxidation. We also observed a reduced mitochondrial membrane potential in SAMP8 mouse astrocytes. Glutamate uptake in astrocytes is a critical neuroprotective mechanism. SAMP8 astrocytes showed a decreased glutamate uptake compared with those of SAMR1 controls. Interestingly, survival of SAMP8 or SAMR1 neurons cocultured with SAMP8 astrocytes was significantly reduced. Our results indicate that alterations in astrocyte cultures from SAMP8 mice are similar to those detected in whole brains of SAMP8 mice at 1-5 months. Moreover, our findings suggest that this in vitro preparation is suitable for studying the molecular and cellular processes underlying early aging in this murine model. In addition, our study supports the contention that astrocytes play a key role in neurodegeneration during the aging process.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

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Dysfunction of astrocytes in senescence‐accelerated mice SAMP8 reduces their neuroprotective capacity

et al. 2008

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“…SAMP8 mice showed agerelated deficits in memory and learning [26,27] and A␤ and tau pathology in brains [28,29]. Furthermore, increased levels of insoluble (aggregated) A␤ and tau were observed in the brains of cognitively impaired SAMP8 mice in this study and others (data not shown), validating this model for assessments of PE859.…”

Section: Resultssupporting

confidence: 82%

PE859, A Novel Curcumin Derivative, Inhibits Amyloid-β and Tau Aggregation, and Ameliorates Cognitive Dysfunction in Senescence-Accelerated Mouse Prone 8

Okuda

Fujita

Hijikuro³

et al. 2017

JAD

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Abstract. Aggregation of amyloid-␤ (A␤) and tau plays a crucial role in the onset and progression of Alzheimer's disease (AD). Therefore, the inhibition of A␤ and tau aggregation may represent a potential therapeutic target for AD. Herein, we designed and synthesized both A␤ and tau dual aggregation inhibitors based on the structure of curcumin and developed the novel curcumin derivative PE859. In this study, we investigated the inhibitory activity of PE859 on A␤ aggregation in vitro and the therapeutic effects of PE859 on cognitive dysfunction via dual inhibition of A␤ and tau aggregation in vivo. PE859 inhibited A␤ aggregation in vitro and protected cultured cells from A␤-induced cytotoxicity. Furthermore, PE859 ameliorated cognitive dysfunction and reduced the amount of aggregated A␤ and tau in brains of senescence-accelerated mouse prone 8 (SAMP8). These results warrant consideration of PE859 as a candidate drug for AD.

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“…For example, Alvarez-Garcia et al [22] found no differences in the activity of catalase and glutathione reductase. A different study in animals of the same age showed the opposite result: glutathione-S-transferase was not affected, but glutathione reductase and catalase were significantly inhibited compared to SAMR1 [31].…”

Section: First Steps In Characterizing Samp8mentioning

confidence: 87%

Senescence-Accelerated Mice P8: A Tool to Study Brain Aging and Alzheimer's Disease in a Mouse Model

Pallàs

2012

ISRN Cell Biology

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The causes of aging remain unknown, but they are probably intimately linked to a multifactorial process that affects cell networks to varying degrees. Although a growing number of aging and Alzheimer's disease (AD) animal models are available, a more comprehensive and physiological mouse model is required. In this context, the senescence-accelerated mouse prone 8 (SAMP8) has a number of advantages, since its rapid physiological senescence means that it has about half the normal lifespan of a rodent. In addition, according to data gathered over the last five years, some of its behavioral traits and histopathology resemble AD human dementia. SAMP8 has remarkable pathological similarities to AD and may prove to be an excellent model for acquiring more in-depth knowledge of the age-related neurodegenerative processes behind brain senescence and AD in particular. We review these facts and particularly the data on parameters related to neurodegeneration. SAMP8 also shows signs of aging in the immune, vascular, and metabolic systems, among others.

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Changes in oxidative stress parameters and neurodegeneration markers in the brain of the senescence-accelerated mice SAMP-8

Cited by 78 publications

References 42 publications

Dysfunction of astrocytes in senescence‐accelerated mice SAMP8 reduces their neuroprotective capacity

Dysfunction of astrocytes in senescence‐accelerated mice SAMP8 reduces their neuroprotective capacity

PE859, A Novel Curcumin Derivative, Inhibits Amyloid-β and Tau Aggregation, and Ameliorates Cognitive Dysfunction in Senescence-Accelerated Mouse Prone 8

Senescence-Accelerated Mice P8: A Tool to Study Brain Aging and Alzheimer's Disease in a Mouse Model

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