Age-related changes in transmitter glutamate and NMDA receptor/channels in the brain of senescence-accelerated mouse

Kitamura, Yoshihisa; Zhao, Xuehui; Ohnuki, Toshio; Takei, Makiko; Nomura, Yasuyuki

doi:10.1016/0304-3940(92)90396-o

Cited by 65 publications

(27 citation statements)

References 16 publications

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“…In our work, ornithine aminotransferase (OAT) and glutamine synthetase (GS), which can prevent ammonia accumulation via biosynthesis of glutamate and glutamine, were found to be up-regulated in both SAMP8-1m and SAMP8-6m. It has been reported previously that 2-month-old SAMP8 began to exhibit high levels of Glu and Gln, indicating abnormal protein metabolism (38). Hyperexpression of OAT from 12-month-old SAMP8 has also been reported (39); this is consistent with the present work.…”

Section: Table II Changed Proteins Identified By Esi-fticr-mssupporting

confidence: 83%

Comparative Studies of Early Liver Dysfunction in Senescence-accelerated Mouse Using Mitochondrial Proteomics Approaches

Liu

et al. 2008

Molecular & Cellular Proteomics

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The liver is a complex and unique organ responsible for a breadth of functions crucial to sustaining life, especially for various metabolic processes in its mitochondria. Senescence-accelerated mouse prone/8 (SAMP8), a widely used aging model, exhibits an oxidative stress-induced aging phenotype and severe mitochondria-related liver pathology that are not seen in senescence-accelerated mouse resistant/1 (SAMR1). Here we used both two-dimensional electrophoresis-and ICAT-based mitochondrial proteomics analysis to view the liver mitochondrial protein alterations between SAMP8 and SAMR1. Compared with SAMR1, decreased expression and activity of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase were detected in SAMP8 at 6 months old (SAMP8-6m). As the key enzyme of ketogenesis, 3-hydroxy-3-methylglutaryl-CoA synthase is well known to be transcriptionally regulated by peroxisome proliferator-activated receptor ␣, which was also expressed at lower levels in SAMP8-6m livers. In addition, down-regulation of two peroxisome proliferator-activated receptor ␣ target gene products (acyl-CoA oxidase and enoyl-CoA hydratase), elevation of triglyceride, and reduction of acetyl-CoA were observed, indicating abnormal fatty acid metabolism in SAMP8-6m livers. In addition eight proteins (NDUAA, NDUBA, NDUB7, NDUS1, NDUS3, NDUV1, ETFA, and UCRI) of mitochondrial complexes were down-regulated in SAMP8-6m, resulting in mitochondria-related liver dysfunction characterized by enhanced oxidative stress-induced molecular damage (lipid peroxide and oxidized protein) and depressed energy production (ATP). Glutamine synthetase and ornithine aminotransferase involved in glutamine synthesis were up-regulated in SAMP8 livers at both 1 and 6 months old that may be related to the accumulation of glutamate and glutamine. Our work provided useful clues to understanding the molecular mechanism underlying liver dysfunction in senescence-accelerated mouse. Molecular & Cellular Proteomics 7:1737-1747, 2008.The liver is regarded as the major organ for a number of physiological presses. As the main energy producers, liver mitochondria are considered to be the central integrators of intermediary metabolism including fatty acid oxidation, the Krebs cycle, oxidative phosphorylation, ketogenesis, and the urea cycle. Furthermore most of the liver disorders have been reported to have increased reactive oxygen species (ROS) 1 and decreased ATP as vital characteristics (1, 2), which are both generated through the mitochondrial respiratory chain.The senescence-accelerated mouse (SAM) model is an aging model obtained by continuous sister-brother breeding from original litters of AKR/J mice (3). SAM includes two strains, i.e. SAM prone (SAMP) and SAM resistant (SAMR). SAMP exhibit a shortened life span and early manifestation of various symptoms of senescence, whereas SAMR are senescence-resistant inbred strains (4). SAMP8, a substrain of SAMP, has become a major biogerontological resource in aging research with SAMR1 as control (5, 6).Recently Ye et al. (7) h...

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Section: Table II Changed Proteins Identified By Esi-fticr-mssupporting

confidence: 83%

Comparative Studies of Early Liver Dysfunction in Senescence-accelerated Mouse Using Mitochondrial Proteomics Approaches

Liu

et al. 2008

Molecular & Cellular Proteomics

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“…SAMP8 presented not only similar characteristics to aged humans, such as shorter lifespan, lordosis, reduced physical activity, and hair loss [46,47], but also some neurodegenerative features, such as early onset of learning and memory deficits [48], altered emotions and abnormal circadian rhythm [49,50], neuronal cell loss [51], and reduction in the release of neurotransmitters in the brain [52,53]. Besides, impairment of mitochondrial functions has been shown in SAMP8 brain at a relatively early age compared to SAMR1 mice [29].…”

Section: Samp8 Postulated As An Early Model Of Alzheimer's Diseasementioning

confidence: 99%

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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“…These animals exhibit early onset and irreversible advance of senescence, as demonstrated by the loss of normal behaviour, the appearance of skin lesions, increased lordokyphosis and a shortened lifespan (Takeda, 2009). Moreover, the SAMP8 strain manifests learning and memory deficits (Miyamoto 1997), neuronal cell loss (Kawamata et al 1997), gliosis (Nomura and Okuma 1999), a reduction in the release of neurotransmitters in the brain (Kitamura et al 1992) and increased oxidative stress (Zhang et al 2008). Several studies have described an increase in both amyloid β precursor protein (AβPP) and derived β-amyloid (Aβ) peptides in the brain of SAMP8 mice, as well as the presence of Aβ plaques or deposits Morley et al 2000;Takemura et al 1993).…”

Section: Introductionmentioning

confidence: 99%

Presence of a neo-epitope and absence of amyloid beta and tau protein in degenerative hippocampal granules of aged mice

Manich

Valle

Cabezón

et al. 2013

AGE

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Clustered pathological granules related to a degenerative process appear and increase progressively with age in the hippocampus of numerous mouse strains. We describe herein the presence of a neoepitope of carbohydrate nature in these granules, which is not present in other brain areas and thus constitutes a new marker of these degenerative structures. We also found that this epitope is recognised by a contaminant IgM present in several antibodies obtained from mouse ascites and from both mouse and rabbit sera. These findings entail the need to revise the high number of components that are thought to be present in the granules, such as the controversial β-amyloid peptides described in the granules of senescence-accelerated mouse prone-8 (SAMP8) mice. Characterisation of the composition of SAMP8 granules, taking into account the presence of the neo-epitope and the contaminant IgM, showed that granules do not contain either β-amyloid peptides or tau protein. The presence of the neo-epitope in the granules but not in other brain areas opens up a new direction in the study of the neurodegenerative processes associated with age. The SAMP8 strain, in which the progression of the granules is enhanced, may be a useful model for this purpose.

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Age-related changes in transmitter glutamate and NMDA receptor/channels in the brain of senescence-accelerated mouse

Cited by 65 publications

References 16 publications

Comparative Studies of Early Liver Dysfunction in Senescence-accelerated Mouse Using Mitochondrial Proteomics Approaches

Comparative Studies of Early Liver Dysfunction in Senescence-accelerated Mouse Using Mitochondrial Proteomics Approaches

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

Presence of a neo-epitope and absence of amyloid beta and tau protein in degenerative hippocampal granules of aged mice

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