Site-directed antisense oligonucleotide decreases the expression of amyloid precursor protein and reverses deficits in learning and memory in aged SAMP8 mice

Kumar, Vijaya B.; Farr, Susan A.; Flood, James F.; Vyas, Kamlesh; Franko, Mark; Banks, William A.; Morley, John E.

doi:10.1016/s0196-9781(00)00339-9

Cited by 172 publications

(126 citation statements)

References 34 publications

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“…Given the above, the use of SAMP8 animals as a model of AD needs to be based not on amyloid deposition, but on other facts. In this regard, several authors have observed an increase with age of AβPP and its mRNA in the hippocampus of SAMP8 Kumar et al 2000). On the other hand, abnormal levels of phosphorylated tau protein have also been described in 11-month-old SAMP8 mice (Wei et al 1999) and there are higher levels of various forms of hyperphosphorylated tau in SAMP8 compared to SAMR1 (Canudas et al 2005).…”

Section: Discussionmentioning

confidence: 97%

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: 97%

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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“…SAMP8 also exhibit agerelated increases in β-amyloid (Aβ) levels. Moreover, the increase in Aβ may lead to cognitive deficits, because reducing the circulating levels of Aβ reduces oxidative stress and improves learning and memory (Kumar et al 2000;Poon et al 2004). Together with changes in other Alzheimer's disease related markers, such as apolipoprotein E and presenilin-2, the SAMP8 seems to be an attractive animal model for studying the cognitive impairments associated with Alzheimer's disease, as well as normal aging.…”

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confidence: 99%

Age-related disruptions of circadian rhythm and memory in the senescence-accelerated mouse (SAMP8)

Pang

Miller

Fortress

et al. 2006

AGE

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Common complaints of the elderly involve impaired cognitive abilities, such as loss of memory and inability to attend. Although much research has been devoted to these cognitive impairments, other factors such as disrupted sleep patterns and increased daytime drowsiness may contribute indirectly to impaired cognitive abilities. Disrupted sleep-wake cycles may be the result of age-related changes to the internal (circadian) clock. In this article, we review recent research on aging and circadian rhythms with a focus on the senescence-accelerated mouse (SAM) as a model of aging. We explore some of the neurobiological mechanisms that appear to be responsible for our aging clock, and consider implications of this work for age-related changes in cognition.Key words aging . C-Fos . circadian rhythms . mouse . running wheel . SAMP8 . suprachiasmatic nucleus Cognitive impairments are well-known complaints of the elderly. Despite their obvious clinical importance, many questions remain unanswered. One important issue concerns whether cognitive impairments are due to direct alterations in the cognitive function, or to other difficulties that may in turn result in cognitive deficits. For example, the elderly often report poor night-time sleep quality, daytime sleepiness, lack of energy, and difficulty adjusting to a time shift (increased "jet lag"). Could these effects contribute to cognitive impairments?Although a confluence of factors may lead to poor sleep quality, etc., it is likely that one general culprit is aging of the internal (circadian) clock that regulates these behaviors (Munch et al. 2005;Turek et al. 1995;Weitzman et al. 1982). Moreover, evidence suggests that our internal clock may also mediate cognitive functioning (Antoniadis et al. 2000;Brock 1991, Stone 1989van Gool 1986;van Someren et al. 1993a). In this article, we review recent research on aging and circadian rhythms, with a focus on the senescence-accelerated mouse line. We explore some of the neurobiological mechanisms that appear to be responsible for our aging clock, and consider implications of this work for the study of age-related changes in cognition.Circadian rhythms are predictable and regularly occurring daily changes in behavior and physiological states. The term circadian, literally meaning "around a day," has its origins in two Latin words: Circa (around) and dies (day). Two defining characteristics AGE (2006) of circadian rhythms are their continued persistence in the absence of external cues in the environment and their ability to be entrained (synchronized) by environmental cues. With respect to the former property, it is the endogenous (self-sustaining) nature of circadian rhythms that engenders an internal clock. With respect to the latter property, the major external cue that serves to synchronize the circadian rhythms of humans and other mammals is light, but almost any periodic event can act as a Zeitgeber ("time-giver").Research on the biological basis of circadian rhythms in humans and other mammals implicates the s...

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“…Aβ is an initiator of free radical damage. 38) Also, the memory deficit of SAMP8 mice is reversed by administration of antisense Aβ oligonucleotides, 39) which also decreased lipid and protein oxidation in the brains of SAMP8 mice. 40) These results indicate that reducing the Aβ level would decrease oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Aβ induces oxidative stress in senescence-accelerated (SAMP8) mice

Takagane

Nojima

Mitsuhashi

et al. 2015

Bioscience, Biotechnology, and Biochemistry

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According to the amyloid hypothesis, amyloid β accumulates in brains with Alzheimer’s disease (AD) and triggers cell death and memory deficit. Previously, we developed a rice Aβ vaccine expressing Aβ, which reduced brain Aβ levels in the Tg2576 mouse model of familial AD. We used senescence-accelerated SAMP8 mice as a model of sporadic AD and investigated the relationship between Aβ and oxidative stress. Insoluble Aβ and 4-hydroxynonenal (4-HNE) levels tended to be reduced in SAMP8 mice-fed the rice Aβ vaccine. We attempted to clarify the relationship between oxidative stress and Aβ in vitro. Addition of Aβ peptide to the culture medium resulted in an increase in 4-HNE levels in SH-SY5Y cells. Tg2576 mice, which express large amounts of Aβ in their brain, also exhibited increased 4-HNE levels; this increase was inhibited by the Aβ vaccine. These results indicate that Aβ induces oxidative stress in cultured cells and in the mouse brain.

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Site-directed antisense oligonucleotide decreases the expression of amyloid precursor protein and reverses deficits in learning and memory in aged SAMP8 mice

Cited by 172 publications

References 34 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

Age-related disruptions of circadian rhythm and memory in the senescence-accelerated mouse (SAMP8)

Aβ induces oxidative stress in senescence-accelerated (SAMP8) mice

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