Senescence‐Accelerated Mouse

Nomura, Yasuyuki; Yamanaka, Yojiro; Kitamura, Yoshihisa; Arima, Takashi; Ohnuki, Toshio; Osuga, Yutaka; Sasaki, Kohsuke; Nagashima, Kazuo; Ihara, Yasuo

doi:10.1111/j.1749-6632.1996.tb39080.x

Cited by 54 publications

(13 citation statements)

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“…Morley et al (2000) found Aβ plaques that were not discernible before 16 months of age and became more prevalent at 22 months of age. However, Nomura et al (1996) found no evidence of deposits or granular structures in SAMP8 brain although they reported an increase in APP-like immunoreactivity. From their description, the Aβ-LI and reelin deposits containing Aβ reported by Knuesel et al (2009) would appear to be the pathological granules that we have investigated further in the present study.…”

Section: Discussionmentioning

confidence: 88%

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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Section: Discussionmentioning

confidence: 88%

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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“…Learning and memory in the SAMP8 strain has been assessed using several paradigms, including watermaze, T-maze, passive avoidance, and one-way active avoidance tests, with declines in cognitive function evident at 2 months of age, and significantly at 4 months as compared with normal aging SAMR1 mice [16]. In an immunoblot analysis, we found that amyloid precursor protein (APP)-like protein was increased with age in the brain of SAMP8, associated with an increase in gliosis and glial fibrillary acidic protein (GFAP) [9]. Recently, Takemura et al [17] found that b/A4 protein-like immunoreactive granular structures (b-LIGS) increased with age using a polyclonal antibody to b/A4 protein fragments 10-42 in SAMP8 and SAMR1.…”

Section: Introductionmentioning

confidence: 92%

“…Previous studies by ourselves and others revealed reduction in the amounts of neurotransmitters released from brain slices [2,3], decreases in levels of muscarinic acetylcholine, and serotonine-1A and NMDA receptors [4,5], and decreases in protein kinase C [5,6] and synaptic spine density [7]. Genes related to Alzheimer's disease (AD) were found in the SAMP8 brain [8], and b-amyloid (Ab) deposits were found in the brains of aged SAMP8 mice [9,10]. Abnormal granular structures, which stained positively with periodic acid-Schiff (PASpositive granular structures; PGS), have also been observed in the SAMP8 brain [11].…”

Section: Introductionmentioning

confidence: 99%

Neurochemistry, Neuropathology, and Heredity in SAMP8: A Mouse Model of Senescence

Takano

Nomura

2009

Neurochem Res

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The SAMP8 strain spontaneously develops learning and memory deficits with characteristics of aging, and is a good model for studying the mechanism of cognitive dysfunction with age. Oxidative stress occurs systemically in SAMP8 from early on in life and increases with aging. Neuropathological changes such as the deposition of A beta, hyperphosphorylation of tau, impaired development of dendritic spines, and sponge formation, and neurochemical changes were found in the SAMP8 brain. These changes may be partially mediated by oxidative stress. Oxidative damage is a major factor in neurodegenerative disorders and aging. A decline in the respiratory control ratio suggesting mitochondrial dysfunction was found in the brain of SAMP8. The rise in oxidative stress following mitochondrial dysfunction may trigger neuropathological and neurochemical changes, disrupting the development of neural networks in the brain in SAMP8.

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“…In-vitro study using human platelet cells showed a non-significant difference in TSPO density between young and older subjects (Marazziti et al, 1994). However, a radioligand binding assay study using the classical TSPO radioligand [ 3 H]-PK11195 in an animal model of aging showed an age-related increase in TSPO binding in the cerebral cortex and hippocampus (Nomura et al, 1996). …”

Section: Introductionmentioning

confidence: 99%

Neuroinflammation in healthy aging: A PET study using a novel Translocator Protein 18kDa (TSPO) radioligand, [18F]-FEPPA

et al. 2014

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One of the cellular markers of neuroinflammation is increased microglia activation, characterized by overexpression of mitochondrial 18 kDa Translocator Protein (TSPO). TSPO expression can be quantified in-vivo using the positron emission tomography (PET) radioligand [18F]-FEPPA. This study examined microglial activation as measured with [18F]-FEPPA PET across the adult lifespan in a group of healthy volunteers. We performed genotyping for the rs6971 TS.PO gene polymorphism to control for the known variability in binding affinity. Thirty-three healthy volunteers (age range: 19–82 years; 22 high affinity binders (HAB), 11 mixed affinity binders (MAB)) underwent [18F]-FEPPA PET scans, acquired on the High Resolution Research Tomograph (HRRT) and analyzed using a 2-tissue compartment model. Regression analyses were performed to examine the effect of age adjusting for genetic status on [18F]-FEPPA total distribution volumes (VT) in the hippocampus, temporal, and prefrontal cortex. We found no significant effect of age on [18F]-FEPPA VT (F (1,30) = 0.918; p = 0.346), and a significant effect of genetic polymorphism (F (1,30) = 8.767; p = 0.006). This is the first in-vivo study to evaluate age-related changes in TSPO binding, using the new generation TSPO radioligands. Increased neuroinflammation, as measured with [18F]-FEPPA PET was not associated with normal aging, suggesting that healthy elderly individuals may serve as useful benchmark against patients with neurodegenerative disorders where neuroinflammation may be present.

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Senescence‐Accelerated Mouse

Cited by 54 publications

References 0 publications

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

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

Neurochemistry, Neuropathology, and Heredity in SAMP8: A Mouse Model of Senescence

Neuroinflammation in healthy aging: A PET study using a novel Translocator Protein 18kDa (TSPO) radioligand, [18F]-FEPPA

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